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Clinical Trial Results:
A Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study Evaluating the Safety and Efficacy of Baricitinib in Combination with Topical Corticosteroids in Adult Patients with Moderate-to-Severe Atopic Dermatitis Who Have Experienced Failure to Cyclosporine or Are Intolerant to, or Have Contraindication to, Cyclosporine

Summary
EudraCT number	2017-004574-34
Trial protocol	GB NL FR AT BE PL FI ES IT
Global end of trial date	20 Apr 2023

Results information
Results version number	v2(current)
This version publication date	05 May 2024
First version publication date	13 Dec 2020
Other versions	v1
Version creation reason	New data added to full data set New data added to full data set

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

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Trial information

Top of page

Sponsor protocol code

I4V-MC-JAIN

ISRCTN number

US NCT number

NCT01624259

WHO universal trial number (UTN)

Other trial identifiers

Trial Number: 16841

Sponsor organisation name

Eli Lilly and Company

Sponsor organisation address

Lilly Corporate Center, Indianapolis, IN, United States, 46285

Public contact

Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐CTLilly,

Scientific contact

Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐285‐4559,

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

19 Sep 2019

Is this the analysis of the primary completion data?

Yes

Primary completion date

19 Sep 2019

Global end of trial reached?

Yes

Global end of trial date

20 Apr 2023

Was the trial ended prematurely?

Main objective of the trial

The purpose of this study is to determine the efficacy and safety of baricitinib in combination with topical corticosteroids in participants with moderate to severe atopic dermatitis who have experienced failure to cyclosporine or are intolerant to, or have contraindication to cyclosporine.

Protection of trial subjects

This study was conducted in accordance with International Conference on Harmonization (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.

Background therapy

Evidence for comparator

Actual start date of recruitment

15 May 2018

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Austria: 10

Country: Number of subjects enrolled

Netherlands: 16

Country: Number of subjects enrolled

Belgium: 26

Country: Number of subjects enrolled

Finland: 7

Country: Number of subjects enrolled

Poland: 41

Country: Number of subjects enrolled

Brazil: 48

Country: Number of subjects enrolled

Italy: 37

Country: Number of subjects enrolled

France: 39

Country: Number of subjects enrolled

Germany: 88

Country: Number of subjects enrolled

Japan: 79

Country: Number of subjects enrolled

Russian Federation: 14

Country: Number of subjects enrolled

Spain: 35

Country: Number of subjects enrolled

United Kingdom: 19

Country: Number of subjects enrolled

Switzerland: 4

Worldwide total number of subjects

463

EEA total number of subjects

318

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)

448

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

At Week 52: responders (IGA 0 or 1) and partial responders (PR) (IGA 2) randomized to Baricitinib (Bari) 4mg or 2mg, without use of high potency TCS in the previous 14 days, were enrolled into the substudy.

Screening details

Responders (IGA 0 or 1) and PR (IGA 2) who received Bari 4mg, 2mg, 1mg or PBO and not eligible for the substudy remained on their dose. If worsening of the symptoms occurred (IGA ≥3), those receiving PBO, Bari 2mg or 1mg were rerandomized to Bari 4mg or 2mg. Nonresponders (IGA ≥ 3) in the PBO, Bari 2mg or 1mg were rerandomized to Bari 4mg or 2mg.

Period 1 title

Double-Blind Treatment Week 0 to Week 52

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Investigator, Subject

Are arms mutually exclusive

Yes

Placebo

Arm description

Placebo administered orally once daily in combination with topical corticosteroids.

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

Placebo administered orally once daily.

1 mg Baricitinib

Arm description

1 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Arm type

Experimental

Investigational medicinal product name

Baricitinib

Investigational medicinal product code

Other name

LY3009104

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

1 mg Baricitinib administered orally once daily.

2 mg Baricitinib

Arm description

2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Arm type

Experimental

Investigational medicinal product name

Baricitinib

Investigational medicinal product code

Other name

LY3009104

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

2 mg Baricitinib administered orally once daily.

4 mg Baricitinib

Arm description

4 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Arm type

Placebo

Investigational medicinal product name

Baricitinib

Investigational medicinal product code

Other name

LY3009104

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

4 mg Baricitinib administered orally once daily.

Number of subjects in period 1	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Started	93	93	185	92
Received at Least One Dose of Study Drug	93	93	184	92
Completed	72	80	173	85
Not completed	21	13	12	7
Consent withdrawn by subject	4	-	-	-
Physician decision	-	1	-	-
Adverse event, non-fatal	1	-	3	1
Lack of efficacy	16	10	7	6
Protocol deviation	-	2	2	-

Period 2 title

Long-Term Extension Week 52 to Week 200

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

LTE Substudy 4 mg Baricitinib to 4 mg Baricitinib

Arm description

LTE Substudy 4 mg Baricitinib to 4 mg Baricitinib (Responders/Partial Responders) 4 mg Baricitinib administered orally once daily (continued previous dose) in combination with topical corticosteroids (TCS). Placebo administered orally to maintain the blind.

Arm type

Experimental

Investigational medicinal product name

Baricitinib

Investigational medicinal product code

LY3009104

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

4 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

LTE Substudy 4 mg Baricitinib to 2 mg Baricitinib

Arm description

LTE Substudy 4 mg Baricitinib to 2 mg Baricitinib (Responders/Partial Responders) 4 mg Baricitinib rerandomized to 2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Arm type

Experimental

Investigational medicinal product name

2 mg Baricitinb

Investigational medicinal product code

LY3009104

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

4 mg Baricitinib rerandomized to 2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

LTE Substudy 2 mg Baricitinib to 2 mg Baricitinib

Arm description

LTE Substudy 2 mg Baricitinib to 2 mg Baricitinib (Responders/Partial Responders) 2 mg Baricitinib rerandomized to 2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Arm type

Experimental

Investigational medicinal product name

2 mg Baricitinb

Investigational medicinal product code

LY3009104

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

2 mg Baricitinib rerandomized to 2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

LTE Substudy 2 mg Baricitinib to 1 mg Baricitinib

Arm description

LTE Substudy 2 mg Baricitinib to 1 mg Baricitinib (Responders/Partial Responders) 2 mg Baricitinib rerandomized to 1 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Arm type

Experimental

Investigational medicinal product name

Baricitinib

Investigational medicinal product code

LY3009104

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

2 mg Baricitinib rerandomized to 1 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

LTE 4 mg Baricitinib (Responders/Partial Responders)

Arm description

LTE 4 mg Baricitinib (Responders/Partial Responders) - Did Not Enter Substudy. 4 mg Baricitinib administered orally once daily (continued previous dose) in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Arm type

Experimental

Investigational medicinal product name

Baricitinib

Investigational medicinal product code

LY3009104

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

4 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

LTE 2 mg Baricitinib (Responders/Partial Responders)

Arm description

LTE 2 mg Baricitinib (Responders/Partial Responders) - Did Not Enter Substudy 2 mg Baricitinib administered orally once daily (continued previous dose) in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Arm type

Experimental

Investigational medicinal product name

2 mg Baricitinb

Investigational medicinal product code

LY3009104

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

LTE 1 mg Baricitinib (Responders/Partial Responders)

Arm description

LTE 1 mg Baricitinib (Responders/Partial Responders) - Did Not Enter Substudy Placebo administered orally once daily (continued previous dose) in combination with topical corticosteroids. Additional placebo administered orally to maintain the blind.

Arm type

Experimental

Investigational medicinal product name

Baricitinib

Investigational medicinal product code

LY3009104

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

1 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

LTE Placebo (Responders/Partial Responders)

Arm description

LTE Placebo (Responders/Partial Responders) - Did Not Enter Substudy Placebo administered orally once daily in combination with topical corticosteroids. Additional placebo administered orally to maintain the blind.

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

Placebo administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

LTE 4 mg Baricitinib (Non-Responders)

Arm description

LTE 4 mg Baricitinib (Non-Responders) - Did not Enter Substudy 4 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Arm type

Experimental

Investigational medicinal product name

Baricitinib

Investigational medicinal product code

LY3009104

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

4 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

LTE 2 mg Baricitinib to 2 mg Baricitinib (Non-Responders)

Arm description

LTE 2 mg Baricitinib to 2 mg Baricitinib (Non-Responders) - Did Not Enter Substudy 2 mg Baricitinib rerandomized to 2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Arm type

Experimental

Investigational medicinal product name

2 mg Baricitinb

Investigational medicinal product code

LY3009104

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

LTE 2 mg Baricitinib to 4 mg Baricitinib (Non-responders)

Arm description

LTE 2 mg Baricitinib to 4 mg Baricitinib (Non-responders) - Did Not Enter Substudy 2 mg Baricitinib rerandomized to 4 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Arm type

Experimental

Investigational medicinal product name

2 mg Baricitinb

Investigational medicinal product code

LY3009104

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

LTE 1 mg Baricitinib to 2 mg Baricitinib (Non-responders)

Arm description

LTE 1 mg Baricitinib to 2 mg Baricitinib (Non-responders) - Did Not Enter Substudy 1 mg Baricitinib rerandomized to 2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Arm type

Experimental

Investigational medicinal product name

Baricitinib

Investigational medicinal product code

LY3009104

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

1 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

LTE 1 mg Baricitinib to 4 mg Baricitinib (Non-responders)

Arm description

LTE 1 mg Baricitinib to 4 mg Baricitinib (Non-responders) - Did Not Enter Study 1 mg Baricitinib rerandomized to 4 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Arm type

Experimental

Investigational medicinal product name

Baricitinib

Investigational medicinal product code

LY3009104

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

1 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

LTE Placebo to 2 mg Baricitinib (Non-responders)

Arm description

LTE Placebo to 2 mg Baricitinib (Non-responders) - Did Not Enter Substudy Placebo rerandomized to 2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Arm type

Experimental

Investigational medicinal product name

Baricitinib

Investigational medicinal product code

LY3009104

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

LTE Placebo to 4 mg Baricitinib (Non-responders)

Arm description

LTE Placebo to 4 mg Baricitinib (Non-responders) - Did Not Enter Substudy Placebo rerandomized to 4 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

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

Placebo administered orally once daily.

Number of subjects in period 2 ^[1]	LTE Substudy 4 mg Baricitinib to 4 mg Baricitinib	LTE Substudy 4 mg Baricitinib to 2 mg Baricitinib	LTE Substudy 2 mg Baricitinib to 2 mg Baricitinib	LTE Substudy 2 mg Baricitinib to 1 mg Baricitinib	LTE 4 mg Baricitinib (Responders/Partial Responders)	LTE 2 mg Baricitinib (Responders/Partial Responders)	LTE 1 mg Baricitinib (Responders/Partial Responders)	LTE Placebo (Responders/Partial Responders)	LTE 4 mg Baricitinib (Non-Responders)	LTE 2 mg Baricitinib to 2 mg Baricitinib (Non-Responders)	LTE 2 mg Baricitinib to 4 mg Baricitinib (Non-responders)	LTE 1 mg Baricitinib to 2 mg Baricitinib (Non-responders)	LTE 1 mg Baricitinib to 4 mg Baricitinib (Non-responders)	LTE Placebo to 2 mg Baricitinib (Non-responders)	LTE Placebo to 4 mg Baricitinib (Non-responders)
Started	16	16	25	24	7	22	34	29	24	27	26	13	14	11	12
Completed	2	6	5	6	3	5	5	10	1	6	4	4	1	1	2
Not completed	14	10	20	18	4	17	29	19	23	21	22	9	13	10	10
Not	-	-	2	-	-	-	-	-	-	-	-	-	-	-	-
Physician decision	-	-	1	-	-	-	-	-	-	-	-	-	-	-	1
Adverse event, non-fatal	-	4	1	2	1	-	1	-	3	1	1	1	2	-	-
Death	-	-	-	1	-	-	-	-	-	-	-	-	-	-	-
Not specified	-	-	-	-	-	-	-	1	-	-	-	-	-	2	1
Study terminated by sponsor	10	4	8	8	3	7	11	11	8	6	12	5	3	1	7
Lost to follow-up	-	-	-	1	-	-	-	2	1	-	2	-	-	1	-
Lack of efficacy	2	2	3	4	-	4	4	-	9	9	6	3	4	4	1
Withdrawal by subject	2	-	5	2	-	6	13	5	2	5	1	-	4	2	-

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Participants who completed the study through Week 52 progressed into the double-blind long-term extension phase.

Baseline characteristics

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Reporting group title

Placebo

Reporting group description

Placebo administered orally once daily in combination with topical corticosteroids.

Reporting group title

1 mg Baricitinib

Reporting group description

1 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Reporting group title

2 mg Baricitinib

Reporting group description

2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Reporting group title

4 mg Baricitinib

Reporting group description

4 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Reporting group values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib	Total
Number of subjects	93	93	185	92	463
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	38.7 ( 13.6 )	38.9 ( 14.0 )	37.3 ( 13.6 )	38.7 ( 13.3 )	-
Gender categorical
Units: Subjects
Female	44	35	52	35	166
Male	49	58	133	57	297
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	11	13	26	14	64
Not Hispanic or Latino	54	62	101	55	272
Unknown or Not Reported	28	18	58	23	127
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	0	0	0
Asian	16	19	36	18	89
Native Hawaiian or Other Pacific Islander	0	0	0	0	0
Black or African American	3	3	2	3	11
White	74	70	145	71	360
More than one race	0	1	2	0	3
Unknown or Not Reported	0	0	0	0	0
Region of Enrollment
Units: Subjects
Austria	1	3	2	4	10
Netherlands	3	0	9	4	16
Belgium	3	5	12	6	26
Finland	2	2	2	1	7
Poland	10	9	15	7	41
Brazil	8	10	20	10	48
Italy	11	9	13	4	37
France	9	6	16	8	39
Germany	15	18	37	18	88
Japan	15	16	32	16	79
Russia	5	2	5	2	14
Spain	7	7	15	6	35
United Kingdom	4	5	6	4	19
Switzerland	0	1	1	2	4

End points

Top of page

Reporting group title

Placebo

Reporting group description

Placebo administered orally once daily in combination with topical corticosteroids.

Reporting group title

1 mg Baricitinib

Reporting group description

1 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Reporting group title

2 mg Baricitinib

Reporting group description

2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Reporting group title

4 mg Baricitinib

Reporting group description

4 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Reporting group title

LTE Substudy 4 mg Baricitinib to 4 mg Baricitinib

Reporting group description

Reporting group title

LTE Substudy 4 mg Baricitinib to 2 mg Baricitinib

Reporting group description

Reporting group title

LTE Substudy 2 mg Baricitinib to 2 mg Baricitinib

Reporting group description

Reporting group title

LTE Substudy 2 mg Baricitinib to 1 mg Baricitinib

Reporting group description

Reporting group title

LTE 4 mg Baricitinib (Responders/Partial Responders)

Reporting group description

Reporting group title

LTE 2 mg Baricitinib (Responders/Partial Responders)

Reporting group description

Reporting group title

LTE 1 mg Baricitinib (Responders/Partial Responders)

Reporting group description

Reporting group title

LTE Placebo (Responders/Partial Responders)

Reporting group description

Reporting group title

LTE 4 mg Baricitinib (Non-Responders)

Reporting group description

Reporting group title

LTE 2 mg Baricitinib to 2 mg Baricitinib (Non-Responders)

Reporting group description

Reporting group title

LTE 2 mg Baricitinib to 4 mg Baricitinib (Non-responders)

Reporting group description

Reporting group title

LTE 1 mg Baricitinib to 2 mg Baricitinib (Non-responders)

Reporting group description

Reporting group title

LTE 1 mg Baricitinib to 4 mg Baricitinib (Non-responders)

Reporting group description

Reporting group title

LTE Placebo to 2 mg Baricitinib (Non-responders)

Reporting group description

Reporting group title

LTE Placebo to 4 mg Baricitinib (Non-responders)

Reporting group description

Subject analysis set title

4 mg Bari to 4 mg Bari LTE Substudy with IGA 0, 1 at Week 52

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants who received at least one study medication during Week 52 to Week 200 in Study JAIN and entered the downtitration substudy with IGA 0 or 1 at Week 52

Subject analysis set title

4 mg Bari to 2 mg Bari LTE Substudy with IGA 0, 1 at Week 52

Subject analysis set type

Sub-group analysis

Subject analysis set description

Substudy population with IGA 0, 1 at Week 52

Subject analysis set title

2 mg Bari to 2 mg Bari LTE Substudy with IGA 0, 1 at Week 52

Subject analysis set type

Sub-group analysis

Subject analysis set description

LTE Substudy with IGA 0, 1 at Week 52

Subject analysis set title

2 mg Bari to 1 mg Bari LTE Substudy with IGA 0, 1 at Week 52

Subject analysis set type

Sub-group analysis

Subject analysis set description

LTE Substudy with IGA 0, 1 at Week 52

Subject analysis set title

4-mg Bari to 4-mg Bari to 4-mg Bari

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants who entered the Substudy and relapsed with an IGA ≥3. Participants randomized to 4 mg Baricitinib in the downtitration substudy who experienced worsening symptoms (IGA increased to ≥3), were retreated with their presubstudy Baricitinib dose.

Subject analysis set title

4 mg Bari to 2 mg Bari to 4 mg Bari

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

2 mg Bari to 2 mg Bari to 2 mg Bari

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants who entered the Substudy and relapsed with an IGA ≥3. Participants randomized to 2 mg Baricitinib in the downtitration substudy who experienced worsening symptoms (IGA increased to ≥3), were retreated with their presubstudy Baricitinib dose.

Subject analysis set title

2 mg Bari to 1 mg Bari to 2 mg Bari

Subject analysis set type

Sub-group analysis

Subject analysis set description

Primary: Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75) (Placebo, 2 mg or 4 mg Baricitinib)

Top of page

End point title

Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75) (Placebo, 2 mg or 4 mg Baricitinib) ^[1]

End point description

The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 (no disease) to 72 (severe disease). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score. Analysis Population Description (APD): All participants randomized to placebo, 2 mg or 4 mg of study drug.

End point type

Primary

End point timeframe

Week 16

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, results reported on Placebo, 2 mg and 4 mg Baricitinib.

End point values	Placebo	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	93	185	92
Units: percentage of participants
number (confidence interval 95%)	17.2 (10.9 to 26.1)	27.6 (21.6 to 34.4)	31.5 (22.9 to 41.6)

EASI75 - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

278

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.071

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.78

Confidence interval

level

95%

sides

2-sided

lower limit

0.95

upper limit

3.32

EASI75 - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.031

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.15

Confidence interval

level

95%

sides

2-sided

lower limit

1.07

upper limit

4.3

Secondary: Percentage of Participants Achieving EASI75 (Placebo, 1 mg Baricitinib)

Top of page

End point title

Percentage of Participants Achieving EASI75 (Placebo, 1 mg Baricitinib) ^[2]

End point description

The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 (no disease) to 72 (severe disease). Missing values were imputed using Non-Responder Imputation (NRI), where non-responders were participants who permanently discontinue, are rescued, or are without at least 1 post-baseline observation. APD: All participants randomized to placebo or 1 mg of study drug.

End point type

Secondary

End point timeframe

Week 16

Notes
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, results reported on Placebo and 1 mg Baricitinib.

End point values	Placebo	1 mg Baricitinib
Number of subjects analysed	93	93
Units: percentage of participants
number (confidence interval 95%)	17.2 (10.9 to 26.1)	22.6 (15.3 to 32.1)

EASI75 - 1 mg

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

186

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.427

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.34

Confidence interval

level

95%

sides

2-sided

lower limit

0.65

upper limit

2.77

Secondary: Percentage of Participants Achieving IGA of 0 or 1 with a ≥ 2 Point Improvement

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End point title

Percentage of Participants Achieving IGA of 0 or 1 with a ≥ 2 Point Improvement

End point description

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	93	93	185	92
Units: percentage of participants
number (confidence interval 95%)	9.7 (5.2 to 17.4)	12.9 (7.5 to 21.2)	15.1 (10.7 to 21.0)	21.7 (14.5 to 31.2)

IGA of 0 or 1 - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

186

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.513

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.35

Confidence interval

level

95%

sides

2-sided

lower limit

0.55

upper limit

3.35

IGA of 0 or 1 - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

278

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.242

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.6

Confidence interval

level

95%

sides

2-sided

lower limit

0.73

upper limit

3.53

IGA of 0 or 1 - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.03

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.54

Confidence interval

level

95%

sides

2-sided

lower limit

1.09

upper limit

5.9

Secondary: Percentage of Participants Achieving EASI90

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End point title

Percentage of Participants Achieving EASI90

End point description

The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 (no disease) to 72 (severe disease). The EASI90 is defined as a ≥ 90% improvement from baseline in the EASI score. APD: All randomized participants.

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	93	93	185	92
Units: percentage of participants
number (confidence interval 95%)	6.5 (3.0 to 13.4)	8.6 (4.4 to 16.1)	10.3 (6.7 to 15.5)	14.1 (8.4 to 22.7)

EASI90 - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

186

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.611

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.32

Confidence interval

level

95%

sides

2-sided

lower limit

0.45

upper limit

3.83

EASI90 - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

278

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.325

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.59

Confidence interval

level

95%

sides

2-sided

lower limit

0.63

upper limit

3.99

EASI90 - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.29

Confidence interval

level

95%

sides

2-sided

lower limit

0.85

upper limit

6.14

Secondary: Percent Change from Baseline in EASI Score

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End point title

Percent Change from Baseline in EASI Score

End point description

The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 (no disease) to 72 (severe disease). Least Squares Mean (LSM) were calculated using mixed model repeated measures (MMRM) model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline score and baseline score-by-visit-interaction as fixed continuous effects.

End point type

Secondary

End point timeframe

Baseline, Week 16 APD: All randomized participants with Week 16 EASI data.

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	54	61	144	65
Units: percent change
least squares mean (standard error)	-42.69 ( 4.135 )	-60.34 ( 4.018 )	-56.05 ( 2.755 )	-63.31 ( 3.922 )

PCFB EASI - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

115

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-17.65

Confidence interval

level

95%

sides

2-sided

lower limit

-28.71

upper limit

-6.58

Variability estimate

Standard error of the mean

Dispersion value

5.627

PCFB EASI - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

198

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-13.35

Confidence interval

level

95%

sides

2-sided

lower limit

-22.83

upper limit

-3.87

Variability estimate

Standard error of the mean

Dispersion value

4.82

PCFB EASI - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

119

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0002

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-20.62

Confidence interval

level

95%

sides

2-sided

lower limit

-31.54

upper limit

-9.7

Variability estimate

Standard error of the mean

Dispersion value

5.554

Secondary: Percentage of Participants Achieving SCORing Atopic Dermatitis 75 (SCORAD75)

Top of page

End point title

Percentage of Participants Achieving SCORing Atopic Dermatitis 75 (SCORAD75)

End point description

The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3)oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with a visual analogue scales (VAS) where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), & subjective symptoms (C: 0-20) combine using A/5 + 7*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. The SCORAD75 responder is defined as a participant who achieves a ≥ 75% improvement from baseline in the SCORAD score. APD: All randomized participants.

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	93	93	185	92
Units: percentage of participants
number (confidence interval 95%)	1.1 (0.2 to 5.8)	6.5 (3.0 to 13.4)	8.1 (5.0 to 12.9)	6.5 (3.0 to 13.5)

SCORAD75 - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

186

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.115

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.14

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

24.29

SCORAD75 - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

278

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.037

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

5.85

Confidence interval

level

95%

sides

2-sided

lower limit

1.11

upper limit

30.88

SCORAD75 - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.083

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.78

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

28.08

Secondary: Percentage of Participants Achieving a 4-Point Improvement in Itch Numeric Rating Scale (NRS)

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End point title

Percentage of Participants Achieving a 4-Point Improvement in Itch Numeric Rating Scale (NRS)

End point description

The Itch NRS is a participant-administered, 11-point horizontal scale anchored at 0 and 10, with 0 representing "no itch" and 10 representing "worst itch imaginable." Overall severity of a participant's itching is indicated by selecting the number, using a daily diary, that best describes the worst level of itching in the past 24 hours. All randomized participants with a baseline Itch NRS score >=4.

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	85	78	166	76
Units: percentage of participants
number (confidence interval 95%)	8.2 (4.0 to 16.0)	23.1 (15.1 to 33.6)	22.9 (17.2 to 29.9)	38.2 (28.1 to 49.4)

NRS - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

163

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.012

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.28

Confidence interval

level

95%

sides

2-sided

lower limit

1.29

upper limit

8.32

NRS - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

251

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.71

Confidence interval

level

95%

sides

2-sided

lower limit

1.59

upper limit

8.66

NRS - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

161

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.00002

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

6.85

Confidence interval

level

95%

sides

2-sided

lower limit

2.79

upper limit

16.82

Secondary: Change from Baseline in the Score of Item 2 of the Atopic Dermatitis Sleep Scale (ADSS)

Top of page

End point title

Change from Baseline in the Score of Item 2 of the Atopic Dermatitis Sleep Scale (ADSS)

End point description

The ADSS is a 3-item, participant-administered questionnaire developed to assess the impact of itch on sleep including difficulty falling asleep due to itch, frequency of waking due to itch, and difficulty getting back to sleep last night due to itch. Item 2 frequency of waking last night is reported by selecting the number of times they woke up each night, ranging from 0 to 29 times, where the higher a number indicates a worse outcome. The ADSS is designed to be completed daily, using a daily diary, with respondents thinking about sleep "last night." Each item is scored individually. LS Mean were calculated using an MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical and baseline and baseline-by-visit-interaction as fixed continuous effects. All randomized participants with Week 16 ADSS Item 2 (frequency of waking) data.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	53	62	135	66
Units: units on a scale
least squares mean (standard error)	-0.63 ( 0.149 )	-1.05 ( 0.142 )	-0.85 ( 0.099 )	-1.42 ( 0.140 )

Change from Baseline (CFB) ADSS - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

115

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.039

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.42

Confidence interval

level

95%

sides

2-sided

lower limit

-0.82

upper limit

-0.02

Variability estimate

Standard error of the mean

Dispersion value

0.203

CFB ADSS - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

188

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.23

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.21

Confidence interval

level

95%

sides

2-sided

lower limit

-0.56

upper limit

0.13

Variability estimate

Standard error of the mean

Dispersion value

0.175

CFB ADSS - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

119

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.79

Confidence interval

level

95%

sides

2-sided

lower limit

-1.18

upper limit

-0.39

Variability estimate

Standard error of the mean

Dispersion value

0.201

Secondary: Change from Baseline in Skin Pain NRS

Top of page

End point title

Change from Baseline in Skin Pain NRS

End point description

Skin Pain NRS is a participant-administered,11-point horizontal scale anchored at 0 and 10, with 0 representing "no pain" and 10 representing "worst pain imaginable." Overall severity of a participant's skin pain is indicated by selecting the number, using a daily diary, that best describes the worst level of skin pain in the past 24 hours. LS Mean were calculated using MMRM model includes treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects. APD: All randomized participants with Week 16 Skin Pain NRS data.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	53	62	135	66
Units: units on a scale
least squares mean (standard error)	-1.56 ( 0.284 )	-2.27 ( 0.274 )	-2.40 ( 0.193 )	-3.02 ( 0.271 )

CFB Skin Pain NRS - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

115

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0714

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.47

upper limit

0.06

Variability estimate

Standard error of the mean

Dispersion value

0.388

CFB Skin Pain NRS - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

188

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0134

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.84

Confidence interval

level

95%

sides

2-sided

lower limit

-1.5

upper limit

-0.17

Variability estimate

Standard error of the mean

Dispersion value

0.337

CFB Skin Pain NRS - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

119

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0002

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.45

Confidence interval

level

95%

sides

2-sided

lower limit

-2.21

upper limit

-0.69

Variability estimate

Standard error of the mean

Dispersion value

0.386

Secondary: Percentage of Participants Achieving IGA of 0 or 1 with a >=2-point improvement

Top of page

End point title

Percentage of Participants Achieving IGA of 0 or 1 with a >=2-point improvement

End point description

End point type

Secondary

End point timeframe

24 Weeks

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	93	93	185	92
Units: percentage of participants
number (confidence interval 95%)	12.9 (7.5 to 21.2)	20.4 (13.5 to 29.7)	18.9 (13.9 to 25.2)	13.0 (7.6 to 21.4)

IGA of 0 or 1 - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

186

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.183

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.71

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

3.75

IGA of 0 or 1 - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

278

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.235

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.54

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

3.11

IGA of 0 or 1 - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.991

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.01

Confidence interval

level

95%

sides

2-sided

lower limit

0.43

upper limit

2.36

Secondary: Percentage of Participants Achieving EASI50

Top of page

End point title

Percentage of Participants Achieving EASI50

End point description

The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 (no disease) to 72 (severe disease). The EASI50 is defined as a ≥ 50% improvement from baseline in the EASI score. APD: All randomized participants.

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	93	93	185	92
Units: percentage of participants
number (confidence interval 95%)	35.5 (26.5 to 45.6)	45.2 (35.4 to 55.3)	51.4 (44.2 to 58.5)	52.2 (42.1 to 62.1)

EASI50 - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

186

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.263

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.41

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

2.57

EASI50 - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

278

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.016

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.89

Confidence interval

level

95%

sides

2-sided

lower limit

1.13

upper limit

3.19

EASI50 - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.031

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.93

Confidence interval

level

95%

sides

2-sided

lower limit

1.06

upper limit

3.52

Secondary: Percentage of Participants Achieving EASI75

Top of page

End point title

Percentage of Participants Achieving EASI75

End point description

End point type

Secondary

End point timeframe

Week 24

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	93	93	185	92
Units: percentage of participants
number (confidence interval 95%)	17.2 (10.9 to 26.1)	30.1 (21.7 to 40.1)	27.6 (21.6 to 34.4)	25.0 (17.3 to 34.7)

EASI75 - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

186

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.058

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.97

Confidence interval

level

95%

sides

2-sided

lower limit

0.98

upper limit

3.96

EASI75 - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

278

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.072

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.77

Confidence interval

level

95%

sides

2-sided

lower limit

0.95

upper limit

3.32

EASI75 - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.224

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.56

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

3.18

Secondary: Percentage of Participants Achieving IGA of 0

Top of page

End point title

Percentage of Participants Achieving IGA of 0

End point description

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	93	93	185	92
Units: percentage of participants
number (confidence interval 95%)	0.00 (0.0 to 4.0)	2.2 (0.6 to 7.5)	1.1 (0.3 to 3.9)	3.3 (1.1 to 9.2)

IGA of 0 - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

186

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.265

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

5.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.29

upper limit

86.08

IGA of 0 - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

278

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.52

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.54

Confidence interval

level

95%

sides

2-sided

lower limit

0.15

upper limit

43.09

IGA of 0 - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.164

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

7.17

Confidence interval

level

95%

sides

2-sided

lower limit

0.45

upper limit

99.99

Secondary: Change from Baseline in SCORAD

Top of page

End point title

Change from Baseline in SCORAD

End point description

The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3) oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with VAS where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), & subjective symptoms (C: 0-20) combine using A/5 + 7*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. LS Mean were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.

End point type

Secondary

End point timeframe

Baseline, Week 16 APD: All randomized participants with Week 16 SCORAD data.

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	54	60	142	64
Units: units on a scale
least squares mean (standard error)	-21.98 ( 2.171 )	-28.06 ( 2.097 )	-28.54 ( 1.438 )	-31.74 ( 2.052 )

CFB SCORAD - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.04

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-6.08

Confidence interval

level

95%

sides

2-sided

lower limit

-11.88

upper limit

-0.29

Variability estimate

Standard error of the mean

Dispersion value

2.948

CFB SCORAD - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

196

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.01

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-6.56

Confidence interval

level

95%

sides

2-sided

lower limit

-11.54

upper limit

-1.58

Variability estimate

Standard error of the mean

Dispersion value

2.533

CFB SCORAD - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-9.77

Confidence interval

level

95%

sides

2-sided

lower limit

-15.51

upper limit

-4.03

Variability estimate

Standard error of the mean

Dispersion value

2.919

Secondary: Percentage of Participants Achieving SCORAD90

Top of page

End point title

Percentage of Participants Achieving SCORAD90

End point description

The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3)oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with a visual analogue scales (VAS) where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), & subjective symptoms (C: 0-20) combine using A/5 + 7*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. The SCORAD90 responder is defined as a participant who achieves a ≥ 90% improvement from baseline in the SCORAD score. APD: All randomized participants.

End point type

Secondary

End point timeframe

Week 16 APD: All randomized participants.

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	93	93	185	92
Units: percentage of participants
number (confidence interval 95%)	0.00 (0.0 to 4.0)	2.2 (0.6 to 7.5)	1.1 (0.3 to 3.9)	2.2 (0.6 to 7.6)

SCORAD90 - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

186

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.265

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.75

Confidence interval

level

95%

sides

2-sided

lower limit

0.31

upper limit

73.93

SCORAD90 - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

278

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.511

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.16

upper limit

38.4

SCORAD90 - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.253

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.32

upper limit

77.11

Secondary: Change from Baseline in Body Surface Area (BSA) Affected

Top of page

End point title

Change from Baseline in Body Surface Area (BSA) Affected

End point description

The BSA affected by AD will be assessed for 4 separate body regions and is collected as part of the EASI assessment: head and neck, trunk (including genital region), upper extremities, and lower extremities (including the buttocks). Each body region will be assessed for disease extent ranging from 0% to 100% involvement. The overall total percentage will be reported based off of all 4 body regions combined, after applying specific multipliers to the different body regions to account for the percent of the total BSA represented by each of the 4 regions. Use the percentage of skin affected for each region (0 to 100%) in EASI as follows: BSA Total = 0.1*BSAhead and neck + 0.3*BSAtrunk + 0.2* BSAupper limbs + 0.4*BSAlower limbs. LS Mean were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline-by-visit-interaction as fixed continuous effects.

End point type

Secondary

End point timeframe

Baseline, Week 16 APD: All randomized participants with Week 16 BSA data.

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	54	61	144	65
Units: units on a scale
least squares mean (standard error)	-19.76 ( 2.257 )	-25.98 ( 2.178 )	-25.26 ( 1.488 )	-28.17 ( 2.125 )

CFB BSA - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

115

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.044

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-6.21

Confidence interval

level

95%

sides

2-sided

lower limit

-12.26

upper limit

-0.16

Variability estimate

Standard error of the mean

Dispersion value

3.078

CFB BSA - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

198

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.037

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-5.5

Confidence interval

level

95%

sides

2-sided

lower limit

-10.67

upper limit

-0.32

Variability estimate

Standard error of the mean

Dispersion value

2.632

CFB BSA - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

119

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-8.41

Confidence interval

level

95%

sides

2-sided

lower limit

-14.37

upper limit

-2.45

Variability estimate

Standard error of the mean

Dispersion value

3.03

Secondary: Percentage of Participants Developing Skin Infections Requiring Antibiotic Treatment

Top of page

End point title

Percentage of Participants Developing Skin Infections Requiring Antibiotic Treatment

End point description

Percentage of participants developing skin infections requiring antibiotic treatment. APD: All randomized participants who received at least one dose of study drug and who did not discontinue from the study for the reason of "Lost to Follow-up" at the first post-baseline visit.

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	93	93	184	92
Units: percentage of participants
number (not applicable)	5.4	6.5	6.5	5.4

Skin Infections - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

186

Analysis specification

Pre-specified

Analysis type

superiority

P-value

> 0.999

Method

Fisher exact

Confidence interval

Skin Infections - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

277

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.797

Method

Fisher exact

Confidence interval

Skin Infections - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

superiority

P-value

> 0.999

Method

Fisher exact

Confidence interval

Secondary: Mean Number of Days without Topical Corticosteroids (TCS) Use

Top of page

End point title

Mean Number of Days without Topical Corticosteroids (TCS) Use

End point description

The ANCOVA model includes treatment, region, and baseline disease severity (IGA) as factors. APD: All randomized participants without use of TCS.

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	89	92	178	89
Units: days
least squares mean (standard error)	12.18 ( 3.39 )	20.80 ( 3.37 )	17.65 ( 2.53 )	19.43 ( 3.41 )

TCS - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.056

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

8.62

Confidence interval

level

95%

sides

2-sided

lower limit

-0.22

upper limit

17.45

Variability estimate

Standard error of the mean

Dispersion value

4.49

TCS - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

267

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.164

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

5.48

Confidence interval

level

95%

sides

2-sided

lower limit

-2.24

upper limit

13.19

Variability estimate

Standard error of the mean

Dispersion value

3.92

TCS - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

178

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.11

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

7.25

Confidence interval

level

95%

sides

2-sided

lower limit

-1.66

upper limit

16.15

Variability estimate

Standard error of the mean

Dispersion value

4.53

Secondary: Mean Gram Quantity of Low and Moderate Potency Background Topical Corticosteroid (TCS) Used (Tube Weights)

Top of page

End point title

Mean Gram Quantity of Low and Moderate Potency Background Topical Corticosteroid (TCS) Used (Tube Weights)

End point description

Average weights of full tubes were used to determine the dispensed weights for each region. Returned tubes were weighed with cap without carton to determine the amount of TCS in grams (g) used at each visit. Analysis was done via analysis of variance (ANOVA), with geographic region, baseline disease severity, and treatment as factors in the model. APD: All randomized participants.

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	93	93	185	92
Units: grams
least squares mean (standard error)	242.59 ( 27.60 )	194.53 ( 27.42 )	185.70 ( 20.67 )	171.17 ( 27.16 )

Low and Moderate Potency TCS - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

186

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.178

Method

ANOVA

Parameter type

Mean difference (final values)

Point estimate

-48.06

Confidence interval

level

95%

sides

2-sided

lower limit

-118

upper limit

21.88

Variability estimate

Standard error of the mean

Dispersion value

35.63

Low and Moderate Potency TCS - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

278

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.066

Method

ANOVA

Parameter type

Mean difference (final values)

Point estimate

-56.9

Confidence interval

level

95%

sides

2-sided

lower limit

-117.56

upper limit

3.77

Variability estimate

Standard error of the mean

Dispersion value

30.9

Low and Moderate Potency TCS - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.045

Method

ANOVA

Parameter type

Mean difference (final values)

Point estimate

-71.42

Confidence interval

level

95%

sides

2-sided

lower limit

-141.24

upper limit

-1.6

Variability estimate

Standard error of the mean

Dispersion value

35.57

Secondary: Percent Change from Baseline in Itch NRS

Top of page

End point title

Percent Change from Baseline in Itch NRS

End point description

The Itch NRS is a participant-administered, 11-point horizontal scale, with 0 representing "no itch" and 10 representing "worst itch imaginable." Overall severity of a participant's itching is indicated by selecting the number, using a daily diary, that best describes the worst level of itching in the past 24 hours. LS Means were calculated using MMRM model with treatment, region, baseline disease severity, visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-interaction as fixed continuous effects. APD: All randomized participants with Week 16 Itch NRS data.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	53	62	135	66
Units: percent change
least squares mean (standard error)	-17.48 ( 4.835 )	-28.80 ( 4.663 )	-32.89 ( 3.258 )	-37.24 ( 4.609 )

PCFB Itch NRS - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

115

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.088

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-11.32

Confidence interval

level

95%

sides

2-sided

lower limit

-24.33

upper limit

1.7

Variability estimate

Standard error of the mean

Dispersion value

6.62

PCFB Itch NRS - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

188

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.007

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-15.41

Confidence interval

level

95%

sides

2-sided

lower limit

-26.67

upper limit

-4.16

Variability estimate

Standard error of the mean

Dispersion value

5.725

PCFB Itch NRS - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

119

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-19.76

Confidence interval

level

95%

sides

2-sided

lower limit

-32.71

upper limit

-6.82

Variability estimate

Standard error of the mean

Dispersion value

6.583

Secondary: Percent Change From Baseline in Itch NRS at Week 24

Top of page

End point title

Percent Change From Baseline in Itch NRS at Week 24

End point description

End point type

Secondary

End point timeframe

Baseline, Week 24

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	35	50	108	54
Units: units on a scale
least squares mean (standard error)	-15.35 ( 5.349 )	-29.35 ( 5.039 )	-30.11 ( 3.495 )	-33.16 ( 4.972 )

PCFB Itch NRS - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.055

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-14

Confidence interval

level

95%

sides

2-sided

lower limit

-28.28

upper limit

0.28

Variability estimate

Standard error of the mean

Dispersion value

7.263

PCFB Itch NRS - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

143

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.02

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-14.76

Confidence interval

level

95%

sides

2-sided

lower limit

-27.15

upper limit

-2.38

Variability estimate

Standard error of the mean

Dispersion value

6.297

PCFB Itch NRS - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.014

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-17.82

Confidence interval

level

95%

sides

2-sided

lower limit

-32.01

upper limit

-3.62

Variability estimate

Standard error of the mean

Dispersion value

7.216

Secondary: Change from Baseline in the Total Score of the Patient Oriented Eczema Measure (POEM)

Top of page

End point title

Change from Baseline in the Total Score of the Patient Oriented Eczema Measure (POEM)

End point description

The POEM is a 7-item self-assessment questionnaire that assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) on a scale ranging from 0-4 (0 = no days, 1 = 1-2 days, 2 = 3-4 days, 3 = 5-6 days, 4 = everyday). The sum of the 7 items gives the total POEM score of 0 (absent disease) to 28 (severe disease). High scores are indicative of more severe disease and poor quality of life. LS Mean were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by visit-interactions as fixed continuous effects. APD: All randomized participants with Week 16 POEM data.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	55	62	145	67
Units: units on a scale
least squares mean (standard error)	-4.18 ( 0.907 )	-6.24 ( 0.872 )	-7.27 ( 0.602 )	-9.27 ( 0.855 )

CFB POEM - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

117

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.095

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-2.06

Confidence interval

level

95%

sides

2-sided

lower limit

-4.47

upper limit

-0.36

Variability estimate

Standard error of the mean

Dispersion value

1.229

CFB POEM - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.004

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-3.09

Confidence interval

level

95%

sides

2-sided

lower limit

-5.16

upper limit

-1.01

Variability estimate

Standard error of the mean

Dispersion value

1.057

CFB POEM - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-5.09

Confidence interval

level

95%

sides

2-sided

lower limit

-7.48

upper limit

-2.7

Variability estimate

Standard error of the mean

Dispersion value

1.216

Secondary: Change from Baseline in the Patient Global Impression of Severity -Atopic Dermatitis (PGI-S-AD) Score

Top of page

End point title

Change from Baseline in the Patient Global Impression of Severity -Atopic Dermatitis (PGI-S-AD) Score

End point description

The PGI-S-AD is a single-item question asking the participant how they would rate their overall AD symptoms over the past 24 hours, using a daily diary. The 5 categories of responses are "(0) no symptoms", "(1) very mild", "(2) mild" "(3) moderate", and "(4) severe." LS Means were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects. APD: All randomized participants with Week 16 PGI-S-AD data.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	53	62	135	66
Units: units on a scale
least squares mean (standard error)	-0.49 ( 0.107 )	-0.74 ( 0.103 )	-0.77 ( 0.072 )	-1.07 ( 0.101 )

CFB PGI-S-AD - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

115

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.097

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.24

Confidence interval

level

95%

sides

2-sided

lower limit

-0.53

upper limit

0.04

Variability estimate

Standard error of the mean

Dispersion value

0.146

CFB PGI-S-AD - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

188

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.033

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.27

Confidence interval

level

95%

sides

2-sided

lower limit

-0.52

upper limit

-0.02

Variability estimate

Standard error of the mean

Dispersion value

0.126

CFB PGI-S-AD - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

119

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.58

Confidence interval

level

95%

sides

2-sided

lower limit

-0.86

upper limit

-0.29

Variability estimate

Standard error of the mean

Dispersion value

0.145

Secondary: Change from Baseline on the Hospital Anxiety Depression Scale (HADS)

Top of page

End point title

Change from Baseline on the Hospital Anxiety Depression Scale (HADS)

End point description

The HADS is a participant-rated instrument used to assess both anxiety and depression. This instrument consists of 14 item questionnaire, each item is rated on a 4-point scale, giving maximum scores of 21 for anxiety and depression. Scores of 11 or more on either subscale are considered to be a significant 'case' of psychological morbidity, while scores of 8-10 represent 'borderline' and 0-7, 'normal.' LS Mean were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects. APD: All randomized participants with Week 16 HADS data.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	55	62	145	67
Units: units on a scale
least squares mean (standard error)
Anxiety	-0.48 ( 0.382 )	-1.04 ( 0.366 )	-1.59 ( 0.256 )	-1.32 ( 0.362 )
Depression	-0.40 ( 0.383 )	-0.69 ( 0.367 )	-1.03 ( 0.256 )	-1.57 ( 0.362 )

CFB HADS - 1 mg Baricitinib

Statistical analysis description

HADS Anxiety

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

117

Analysis specification

Pre-specified

Analysis type

superiority ^[3]

P-value

= 0.272

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.57

Confidence interval

level

95%

sides

2-sided

lower limit

-1.58

upper limit

0.45

Variability estimate

Standard error of the mean

Dispersion value

0.516

Notes
[3] - Anxiety

CFB HADS - 2 mg Baricitinib

Statistical analysis description

HADS Anxiety

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority ^[4]

P-value

= 0.013

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.12

Confidence interval

level

95%

sides

2-sided

lower limit

-1.99

upper limit

-0.24

Variability estimate

Standard error of the mean

Dispersion value

0.446

Notes
[4] - Anxiety

CFB HADS - 4 mg Baricitinib

Statistical analysis description

HADS Anxiety

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority ^[5]

P-value

= 0.099

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.85

Confidence interval

level

95%

sides

2-sided

lower limit

-1.85

upper limit

0.16

Variability estimate

Standard error of the mean

Dispersion value

0.511

Notes
[5] - Anxiety

CFB HADS - 1 mg Baricitinib

Statistical analysis description

HADS Depression

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

117

Analysis specification

Pre-specified

Analysis type

superiority ^[6]

P-value

= 0.584

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.28

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3

upper limit

0.74

Variability estimate

Standard error of the mean

Dispersion value

0.519

Notes
[6] - Depression

CFB HADS - 2 mg Baricitinib

Statistical analysis description

HADS Depression

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority ^[7]

P-value

= 0.162

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.63

Confidence interval

level

95%

sides

2-sided

lower limit

-1.51

upper limit

0.25

Variability estimate

Standard error of the mean

Dispersion value

0.448

Notes
[7] - Depression

CFB HADS - 4 mg Baricitinib

Statistical analysis description

HADS Depression

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority ^[8]

P-value

= 0.024

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.17

Confidence interval

level

95%

sides

2-sided

lower limit

-2.18

upper limit

-0.15

Variability estimate

Standard error of the mean

Dispersion value

0.515

Notes
[8] - Depression

Secondary: Change from Baseline in the Dermatology Life Quality Index (DLQI)

Top of page

End point title

Change from Baseline in the Dermatology Life Quality Index (DLQI)

End point description

The DLQI is a simple, participant-administered,10 question, validated, quality-of-life questionnaire that covers 6 domains including symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. The recall period of this scale is over the last "week." Response categories include "not at all," "a little," "a lot," and "very much," with corresponding scores of 0, 1, 2, and 3, respectively, and unanswered or "not relevant" responses scored as "0." Scores range from 0 to 30 (“no impact on participant's life” to “extremely large effect on participant's life”), and a 4-point change from baseline is considered as the minimal clinically important difference threshold. LS Means were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.

End point type

Secondary

End point timeframe

Baseline, Week 16 APD: All randomized participants with Week 16 DLQI data.

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	55	62	145	67
Units: units on a scale
least squares mean (standard error)	-4.95 ( 0.752 )	-6.18 ( 0.719 )	-6.57 ( 0.494 )	-7.95 ( 0.705 )

CFB DLQI - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

117

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.228

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.23

Confidence interval

level

95%

sides

2-sided

lower limit

-3.23

upper limit

0.77

Variability estimate

Standard error of the mean

Dispersion value

1.018

CFB DLQI - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.065

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.62

Confidence interval

level

95%

sides

2-sided

lower limit

-3.35

upper limit

0.1

Variability estimate

Standard error of the mean

Dispersion value

0.876

CFB DLQI - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-3.01

Confidence interval

level

95%

sides

2-sided

lower limit

-4.99

upper limit

-1.02

Variability estimate

Standard error of the mean

Dispersion value

1.007

Secondary: Change from Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire

Top of page

End point title

Change from Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire

End point description

The WPAI-AD participant questionnaire was developed to measure the effect of general health and symptom severity on work productivity and regular activities in the 7 days prior to the visit. The WPAI-AD consists of 6 items grouped in 4 domains: absenteeism (work time missed), presenteeism (impairment at work/reduced on-the-job effectiveness), work productivity loss (overall work impairment/absenteeism plus presenteeism), and activity impairment, that range from 0% to 100%, with higher values indicating greater impairment. LS Means were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects. APD: All randomized participants with Week 16 WPAI-AD data.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	55	62	145	67
Units: units on a scale
least squares mean (standard error)
Absenteeism (37, 36, 85, 42)	-4.77 ( 2.365 )	-5.69 ( 2.433 )	-2.98 ( 1.639 )	-4.56 ( 2.258 )
Presenteeism (34, 35, 83, 39)	-14.86 ( 3.182 )	-11.80 ( 3.161 )	-14.56 ( 2.133 )	-14.81 ( 3.000 )
Work Productivity Loss (34, 35, 83, 39)	-13.22 ( 3.560 )	-12.07 ( 3.565 )	-13.07 ( 2.440 )	-14.12 ( 3.396 )
Activity Impairment (55, 62, 145, 67)	-16.46 ( 2.853 )	-18.46 ( 2.729 )	-20.86 ( 1.847 )	-23.92 ( 2.660 )

CFB Absenteeism - 1 mg Baricitinib

Statistical analysis description

Change from Baseline (CFB) Absenteeism

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

117

Analysis specification

Pre-specified

Analysis type

superiority ^[9]

P-value

= 0.784

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.92

Confidence interval

level

95%

sides

2-sided

lower limit

-7.5

upper limit

5.67

Variability estimate

Standard error of the mean

Dispersion value

3.339

Notes
[9] - Change from Baseline (CFB) Absenteeism

CFB Absenteeism - 2 mg Baricitinib

Statistical analysis description

CFB Absenteeism

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority ^[10]

P-value

= 0.525

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

1.79

Confidence interval

level

95%

sides

2-sided

lower limit

-3.75

upper limit

7.34

Variability estimate

Standard error of the mean

Dispersion value

2.813

Notes
[10] - CFB Absenteeism

CFB Absenteeism - 4 mg Baricitinib

Statistical analysis description

CFB Absenteeism

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority ^[11]

P-value

= 0.947

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.21

Confidence interval

level

95%

sides

2-sided

lower limit

-6.11

upper limit

6.53

Variability estimate

Standard error of the mean

Dispersion value

3.204

Notes
[11] - CFB Absenteeism

CFB Presenteeism - 1 mg Baricitinib

Statistical analysis description

CFB Presenteeism

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

117

Analysis specification

Pre-specified

Analysis type

superiority ^[12]

P-value

= 0.488

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

3.06

Confidence interval

level

95%

sides

2-sided

lower limit

-5.62

upper limit

11.74

Variability estimate

Standard error of the mean

Dispersion value

4.409

Notes
[12] - CFB Presenteeism

CFB Presenteeism - 2 mg Baricitinib

Statistical analysis description

CFB Presenteeism

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority ^[13]

P-value

= 0.936

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-7.02

upper limit

7.62

Variability estimate

Standard error of the mean

Dispersion value

3.72

Notes
[13] - CFB Presenteeism

CFB Presenteeism - 4 mg Baricitinib

Statistical analysis description

CFB Presenteeism

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority ^[14]

P-value

= 0.991

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-8.35

upper limit

8.45

Variability estimate

Standard error of the mean

Dispersion value

4.267

Notes
[14] - CFB Presenteeism

CFB Work Productivity Loss - 1 mg Baricitinib

Statistical analysis description

CFB Work Productivity Loss

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

117

Analysis specification

Pre-specified

Analysis type

superiority ^[15]

P-value

= 0.816

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

1.15

Confidence interval

level

95%

sides

2-sided

lower limit

-8.57

upper limit

10.88

Variability estimate

Standard error of the mean

Dispersion value

4.938

Notes
[15] - CFB Work Productivity Loss

CFB Work Productivity Loss - 2 mg Baricitinib

Statistical analysis description

CFB Work Productivity Loss

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority ^[16]

P-value

= 0.971

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.15

Confidence interval

level

95%

sides

2-sided

lower limit

-8.08

upper limit

8.38

Variability estimate

Standard error of the mean

Dispersion value

4.178

Notes
[16] - CFB Work Productivity Loss

CFB Work Productivity Loss - 4 mg Baricitinib

Statistical analysis description

CFB Work Productivity Loss

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority ^[17]

P-value

= 0.852

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-10.36

upper limit

8.56

Variability estimate

Standard error of the mean

Dispersion value

4.804

Notes
[17] - CFB Work Productivity Loss

CFB Activity Impairment - 1 mg Baricitinib

Statistical analysis description

CFB Activity Impairment

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

117

Analysis specification

Pre-specified

Analysis type

superiority ^[18]

P-value

= 0.607

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.99

Confidence interval

level

95%

sides

2-sided

lower limit

-9.61

upper limit

5.63

Variability estimate

Standard error of the mean

Dispersion value

3.877

Notes
[18] - CFB Activity Impairment

CFB Activity Impairment - 2 mg Baricitinib

Statistical analysis description

CFB Activity Impairment

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority ^[19]

P-value

= 0.186

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-4.4

Confidence interval

level

95%

sides

2-sided

lower limit

-10.92

upper limit

2.12

Variability estimate

Standard error of the mean

Dispersion value

3.319

Notes
[19] - CFB Activity Impairment

CFB Activity Impairment - 4 mg Baricitinib

Statistical analysis description

CFB Activity Impairment

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority ^[20]

P-value

= 0.052

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-7.45

Confidence interval

level

95%

sides

2-sided

lower limit

-14.96

upper limit

0.06

Variability estimate

Standard error of the mean

Dispersion value

3.82

Notes
[20] - CFB Activity Impairment

Secondary: Change from Baseline in the European Quality of Life–5 Dimensions–5 Levels (EQ-5D-5L) Index Score United States and United Kingdom Algorithm

Top of page

End point title

Change from Baseline in the European Quality of Life–5 Dimensions–5 Levels (EQ-5D-5L) Index Score United States and United Kingdom Algorithm

End point description

The EQ-5D-5L is a 2-part measurement. The first part is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive the health state index scores using the United Kingdom (UK) algorithm, with scores ranging from -0.594 to 1, and the United States (US) algorithm, with scores ranging from -0.109 to 1, with higher score indicating better health state. LS Means were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects. APD: All randomized participants with EQ-5D-5L US and UK Health scores.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	55	62	145	67
Units: units on a scale
least squares mean (standard error)
US Health State Index	0.04 ( 0.016 )	0.08 ( 0.016 )	0.09 ( 0.011 )	0.11 ( 0.015 )
UK Health State Index	0.06 ( 0.023 )	0.11 ( 0.022 )	0.13 ( 0.016 )	0.15 ( 0.022 )

Health State Index US - 1 mg Baricitinib

Statistical analysis description

CFB US Health State Index

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

117

Analysis specification

Pre-specified

Analysis type

superiority ^[21]

P-value

= 0.131

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.03

Confidence interval

level

95%

sides

2-sided

lower limit

-0.01

upper limit

0.08

Variability estimate

Standard error of the mean

Dispersion value

0.022

Notes
[21] - CFB US Health State Index

Health State Index US - 2 mg Baricitinib

Statistical analysis description

CFB US Health State Index

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority ^[22]

P-value

= 0.017

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.05

Confidence interval

level

95%

sides

2-sided

lower limit

0.01

upper limit

0.08

Variability estimate

Standard error of the mean

Dispersion value

0.019

Notes
[22] - CFB US Health State Index

Health State Index US - 4 mg Baricitinib

Statistical analysis description

CFB US Health State Index

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority ^[23]

P-value

= 0.003

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.06

Confidence interval

level

95%

sides

2-sided

lower limit

0.02

upper limit

0.11

Variability estimate

Standard error of the mean

Dispersion value

0.022

Notes
[23] - CFB US Health State Index

Health State Index UK - 1 mg Baricitinib

Statistical analysis description

CFB UK Health State Index

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

117

Analysis specification

Pre-specified

Analysis type

superiority ^[24]

P-value

= 0.102

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.01

upper limit

0.11

Variability estimate

Standard error of the mean

Dispersion value

0.031

Notes
[24] - CFB UK Health State Index

Health State Index UK - 2 mg Baricitinib

Statistical analysis description

CFB UK Health State Index

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority ^[25]

P-value

= 0.014

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.07

Confidence interval

level

95%

sides

2-sided

lower limit

0.01

upper limit

0.12

Variability estimate

Standard error of the mean

Dispersion value

0.027

Notes
[25] - CFB UK Health State Index

Health State Index UK - 4 mg Baricitinib

Statistical analysis description

CFB UK Health State Index

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority ^[26]

P-value

= 0.003

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.09

Confidence interval

level

95%

sides

2-sided

lower limit

0.03

upper limit

0.15

Variability estimate

Standard error of the mean

Dispersion value

0.031

Notes
[26] - CFB UK Health State Index

Secondary: Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Visual Analog Score (VAS)

Top of page

End point title

Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Visual Analog Score (VAS)

End point description

EQ-5D-5L is a 2-part measurement. The second part is assessed using a visual analog scale (VAS) that ranged from 0 to 100 millimeter (mm), where 0 is the worst health you can imagine and 100 is the best health you can imagine. LS Means were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interactions as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects. APD: All randomized participants with Week 16 EQ-5D-5L VAS data.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	55	62	145	67
Units: units on a scale
least squares mean (standard error)	7.64 ( 2.407 )	11.63 ( 2.306 )	8.76 ( 1.588 )	11.03 ( 2.260 )

CFB EQ-5D-5L VAS - 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

117

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.221

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

3.99

Confidence interval

level

95%

sides

2-sided

lower limit

-2.41

upper limit

10.39

Variability estimate

Standard error of the mean

Dispersion value

3.256

CFB EQ-5D-5L VAS - 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.689

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

1.12

Confidence interval

level

95%

sides

2-sided

lower limit

-4.4

upper limit

6.65

Variability estimate

Standard error of the mean

Dispersion value

2.807

CFB EQ-5D-5L VAS - 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.294

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

3.39

Confidence interval

level

95%

sides

2-sided

lower limit

-2.95

upper limit

9.74

Variability estimate

Standard error of the mean

Dispersion value

3.226

Secondary: Percentage of Participants Achieving EASI75

Top of page

End point title

Percentage of Participants Achieving EASI75

End point description

End point type

Secondary

End point timeframe

Week 52

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	93	93	185	92
Units: Percentage of participants
number (confidence interval 95%)	26.9 (18.9 to 36.7)	33.3 (24.6 to 43.4)	30.3 (24.1 to 37.2)	37.0 (27.8 to 47.2)

Placebo, 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

186

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.382

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.33

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

2.54

Placebo, 2 mg Baricitinib

Comparison groups

2 mg Baricitinib v Placebo

Number of subjects included in analysis

278

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.638

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.15

Confidence interval

level

90%

sides

2-sided

lower limit

0.65

upper limit

2.02

Placebo, 4 mg Baricitinib

Comparison groups

Placebo v 4 mg Baricitinib

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.169

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.56

Confidence interval

level

95%

sides

2-sided

lower limit

0.83

upper limit

2.96

Secondary: Percent Change From Baseline in Itch NRS at Week 52

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End point title

Percent Change From Baseline in Itch NRS at Week 52

End point description

End point type

Secondary

End point timeframe

Baseline, Week 52

End point values	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib
Number of subjects analysed	44	54	110	56
Units: Percent change
least squares mean (standard error)	-12.13 ( 7.075 )	-19.49 ( 6.679 )	-16.01 ( 4.279 )	-29.31 ( 6.619 )

Placebo, 1 mg Baricitinib

Comparison groups

Placebo v 1 mg Baricitinib

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.447

Method

Regression, Linear

Parameter type

LS Mean Difference (Final Values)

Point estimate

-7.36

Confidence interval

level

95%

sides

2-sided

lower limit

-26.38

upper limit

11.66

Variability estimate

Standard error of the mean

Dispersion value

9.674

Placebo, 2 mg Baricitinib

Comparison groups

Placebo v 2 mg Baricitinib

Number of subjects included in analysis

154

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.646

Method

Regression, Linear

Parameter type

LS Mean Difference (Final Values)

Point estimate

-3.88

Confidence interval

level

95%

sides

2-sided

lower limit

-20.5

upper limit

12.74

Variability estimate

Standard error of the mean

Dispersion value

8.454

Placebo, 4 mg Baricitinib

Comparison groups

4 mg Baricitinib v Placebo

Number of subjects included in analysis

100

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.075

Method

Regression, Linear

Parameter type

LS Mean Difference (Final Values)

Point estimate

-17.18

Confidence interval

level

95%

sides

2-sided

lower limit

-36.14

upper limit

1.77

Variability estimate

Standard error of the mean

Dispersion value

9.64

Secondary: Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed at 16 Weeks After Rerandomization (Week 68) Randomized Downtitration (All Participants Entering the Substudy)

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End point title

Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed at 16 Weeks After Rerandomization (Week 68) Randomized Downtitration (All Participants Entering the Substudy)

End point description

The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification. All missing values were imputed using modified last observation carried forward (mLOCF). APD: Participants who received at least one study medication during Week 52 to Week 200 in Study JAIN and entered the downtitration substudy. Additionally, those participants who did not meet study discontinuation criteria and continued will be considered in the analysis set.

End point type

Secondary

End point timeframe

Week 68

End point values	LTE Substudy 4 mg Baricitinib to 4 mg Baricitinib	LTE Substudy 4 mg Baricitinib to 2 mg Baricitinib	LTE Substudy 2 mg Baricitinib to 2 mg Baricitinib	LTE Substudy 2 mg Baricitinib to 1 mg Baricitinib
Number of subjects analysed	16	16	25	24
Units: Percentage of participants
number (confidence interval 85%)	93.8 (71.7 to 98.9)	56.3 (33.2 to 76.9)	84.0 (65.3 to 93.6)	50.0 (31.4 to 68.6)

No statistical analyses for this end point

Secondary: Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed at 16 Weeks After Rerandomization (Week 104) Randomized Downtitration (All Participants Entering the Substudy)

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End point title

Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed at 16 Weeks After Rerandomization (Week 104) Randomized Downtitration (All Participants Entering the Substudy)

End point description

End point type

Secondary

End point timeframe

Week 104

End point values	LTE Substudy 4 mg Baricitinib to 4 mg Baricitinib	LTE Substudy 4 mg Baricitinib to 2 mg Baricitinib	LTE Substudy 2 mg Baricitinib to 2 mg Baricitinib	LTE Substudy 2 mg Baricitinib to 1 mg Baricitinib
Number of subjects analysed	16	16	25	24
Units: Percentage of participants
number (confidence interval 95%)	68.8 (44.4 to 85.8)	50.0 (28.0 to 72.0)	72.0 (52.4 to 85.7)	25.0 (12.0 to 44.9)

No statistical analyses for this end point

Secondary: Percentage of Participants With a Response of IGA 0, 1 Assessed at 16 Weeks After Rerandomization (Week 68) Randomized Downtitration (All Participants Entering tSubstudy)

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End point title

Percentage of Participants With a Response of IGA 0, 1 Assessed at 16 Weeks After Rerandomization (Week 68) Randomized Downtitration (All Participants Entering tSubstudy)

End point description

The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification. APD: Participants who received at least one study medication during Week 52 to Week 200 in Study JAIN and entered the downtitration substudy. Additionally, those participants who did not meet study discontinuation criteria and continued will be considered in the analysis set.

End point type

Secondary

End point timeframe

Week 68

End point values	LTE Substudy 4 mg Baricitinib to 4 mg Baricitinib	LTE Substudy 4 mg Baricitinib to 2 mg Baricitinib	LTE Substudy 2 mg Baricitinib to 2 mg Baricitinib	LTE Substudy 2 mg Baricitinib to 1 mg Baricitinib
Number of subjects analysed	16	16	25	24
Units: Percentage of participants
number (confidence interval 95%)	50 (28.0 to 72.0)	25.0 (10.2 to 49.5)	44.0 (26.7 to 62.9)	20.8 (9.2 to 40.5)

No statistical analyses for this end point

Secondary: Percentage of Participants With a Response of IGA 0, 1 Assessed at 16 Weeks After Rerandomization (Week 104) Randomized Downtitration (All Participants Entering the Substudy)

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End point title

Percentage of Participants With a Response of IGA 0, 1 Assessed at 16 Weeks After Rerandomization (Week 104) Randomized Downtitration (All Participants Entering the Substudy)

End point description

The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification. APD: Participants who received at least one study medication during Week 52 to Week 200 in Study JAIN and entered the downtitration substudy. Additionally, those participants who did not meet study discontinuation criteria and continued will be considered in the analysis set.

End point type

Secondary

End point timeframe

Week 104

End point values	LTE Substudy 4 mg Baricitinib to 4 mg Baricitinib	LTE Substudy 4 mg Baricitinib to 2 mg Baricitinib	LTE Substudy 2 mg Baricitinib to 2 mg Baricitinib	LTE Substudy 2 mg Baricitinib to 1 mg Baricitinib
Number of subjects analysed	16	16	25	24
Units: Percentage of participants
number (confidence interval 95%)	43.8 (23.1 to 66.8)	25.0 (10.2 to 49.5)	44.0 (26.7 to 62.9)	8.3 (2.3 to 25.8)

No statistical analyses for this end point

Secondary: Percentage of Participants With a Response of EASI75 From Baseline Assessed at 16 Weeks After Rerandomization (Week 68) Randomized Downtitration (All Participants Entering the Substudy)

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End point title

Percentage of Participants With a Response of EASI75 From Baseline Assessed at 16 Weeks After Rerandomization (Week 68) Randomized Downtitration (All Participants Entering the Substudy)

End point description

The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 (no disease) to 72 (severe disease). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score. APD: Participants who received at least 1 dose of study medication during Week 52 to Week 200 in Study JAIN and entered the downtitration substudy. Those participants who did not meet study discontinuation criteria and continued were included in the analysis.

End point type

Secondary

End point timeframe

Week 68

End point values	LTE Substudy 4 mg Baricitinib to 4 mg Baricitinib	LTE Substudy 4 mg Baricitinib to 2 mg Baricitinib	LTE Substudy 2 mg Baricitinib to 2 mg Baricitinib	LTE Substudy 2 mg Baricitinib to 1 mg Baricitinib
Number of subjects analysed	16	16	25	24
Units: Percentage of participants
number (confidence interval 95%)	75.0 (50.5 to 89.8)	56.3 (33.2 to 76.9)	72.0 (52.4 to 85.7)	41.7 (24.5 to 61.2)

No statistical analyses for this end point

Secondary: Percentage of Participants With a Response of EASI75 From Baseline Assessed at 16 Weeks After Rerandomization (Week 104) Randomized Downtitration (All Participants Entering the Substudy)

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End point title

Percentage of Participants With a Response of EASI75 From Baseline Assessed at 16 Weeks After Rerandomization (Week 104) Randomized Downtitration (All Participants Entering the Substudy)

End point description

The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 (no disease) to 72 (severe disease). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score. APD: Participants who received at least 1 dose of study medication during Week 52 to Week 200 in Study JAIN and entered the downtitration substudy. Those participants who did not meet study discontinuation criteria and continued were included in the analysis.

End point type

Secondary

End point timeframe

Week 104

End point values	LTE Substudy 4 mg Baricitinib to 4 mg Baricitinib	LTE Substudy 4 mg Baricitinib to 2 mg Baricitinib	LTE Substudy 2 mg Baricitinib to 2 mg Baricitinib	LTE Substudy 2 mg Baricitinib to 1 mg Baricitinib
Number of subjects analysed	16	16	25	24
Units: Percentage of participants
number (confidence interval 95%)	68.8 (44.4 to 85.8)	56.3 (33.2 to 76.9)	56.0 (37.1 to 73.3)	33.3 (18.0 to 53.3)

No statistical analyses for this end point

Secondary: Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed at 16 Weeks After Rerandomization (Week 68) Randomized Downtitration (Participants Entering the Substudy With IGA 0 or 1)

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End point title

Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed at 16 Weeks After Rerandomization (Week 68) Randomized Downtitration (Participants Entering the Substudy With IGA 0 or 1)

End point description

The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification. All missing values were imputed using modified last observation carried forward (mLOCF). APD: Participants who received at least one study medication during Week 52 to Week 200 in Study JAIN and entered the downtitration substudy with IGA 0 or 1. Additionally, those participants who did not meet study discontinuation criteria and continued will be considered in the analysis set.

End point type

Secondary

End point timeframe

Week 68

End point values	4 mg Bari to 4 mg Bari LTE Substudy with IGA 0, 1 at Week 52	4 mg Bari to 2 mg Bari LTE Substudy with IGA 0, 1 at Week 52	2 mg Bari to 2 mg Bari LTE Substudy with IGA 0, 1 at Week 52	2 mg Bari to 1 mg Bari LTE Substudy with IGA 0, 1 at Week 52
Number of subjects analysed	10	9	10	9
Units: Percentage of participants
number (confidence interval 95%)	100 (72.2 to 100)	77.8 (45.3 to 93.7)	100 (72.2 to 100)	55.6 (26.7 to 81.1)

No statistical analyses for this end point

Secondary: Percentage of Participants With a Response of IGA 0, 1 or 2 Assessed at 16 Weeks After Rerandomization (Week 104) Randomized Downtitration (Participants Entering the Substudy With IGA 0 or 1)

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End point title

Percentage of Participants With a Response of IGA 0, 1 or 2 Assessed at 16 Weeks After Rerandomization (Week 104) Randomized Downtitration (Participants Entering the Substudy With IGA 0 or 1)

End point description

The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification. All missing values were imputed using mLOCF. APD: Participants who received at least one study medication during Week 52 to Week 200 in Study JAIN and entered the downtitration substudy with IGA 0 or 1. Additionally, those participants who did not meet study discontinuation criteria and continued will be considered in the analysis set.

End point type

Secondary

End point timeframe

Week 104

End point values	4 mg Bari to 4 mg Bari LTE Substudy with IGA 0, 1 at Week 52	4 mg Bari to 2 mg Bari LTE Substudy with IGA 0, 1 at Week 52	2 mg Bari to 2 mg Bari LTE Substudy with IGA 0, 1 at Week 52	2 mg Bari to 1 mg Bari LTE Substudy with IGA 0, 1 at Week 52
Number of subjects analysed	10	9	10	9
Units: Percentage of participants
number (confidence interval 95%)	80.0 (49.0 to 94.3)	66.7 (35.4 to 87.9)	100 (72.2 to 100)	33.3 (12.1 to 64.6)

No statistical analyses for this end point

Secondary: Percentage of Participants With a Response of IGA 0 or 1 Assessed at 16 Weeks After Rerandomization (Week 68) Randomized Downtitration (Participants Entering the Substudy With IGA 0 or 1)

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End point title

Percentage of Participants With a Response of IGA 0 or 1 Assessed at 16 Weeks After Rerandomization (Week 68) Randomized Downtitration (Participants Entering the Substudy With IGA 0 or 1)

End point description

The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification. All missing values were imputed using mLOCF. APD: Participants who received at least one study medication during Week 52 to Week 200 in Study JAIN and entered the downtitration substudy with IGA 0 or 1. Additionally, those participants who did not meet study discontinuation criteria and continued were included in the analysis set.

End point type

Secondary

End point timeframe

Week 68

End point values	4 mg Bari to 4 mg Bari LTE Substudy with IGA 0, 1 at Week 52	4 mg Bari to 2 mg Bari LTE Substudy with IGA 0, 1 at Week 52	2 mg Bari to 2 mg Bari LTE Substudy with IGA 0, 1 at Week 52	2 mg Bari to 1 mg Bari LTE Substudy with IGA 0, 1 at Week 52
Number of subjects analysed	10	9	10	9
Units: Percentage of participants
number (confidence interval 95%)	60.0 (31.3 to 83.2)	33.3 (12.1 to 64.6)	90.0 (59.6 to 98.2)	55.6 (26.7 to 81.1)

No statistical analyses for this end point

Secondary: Percentage of Participants With a Response of IGA 0 or 1 Assessed at 16 Weeks After Rerandomization (Week 104) Randomized Downtitration (Participants Entering the Substudy With IGA 0 or 1)

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End point title

Percentage of Participants With a Response of IGA 0 or 1 Assessed at 16 Weeks After Rerandomization (Week 104) Randomized Downtitration (Participants Entering the Substudy With IGA 0 or 1)

End point description

The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification. All missing values were imputed using mLOCF. APD: Participants who received at least one study medication during Week 52 to Week 200 in Study JAIN and entered the downtitration substudy with IGA 0 or 1. Additionally, those participants who did not meet study discontinuation criteria and continued will be considered in the analysis set.

End point type

Secondary

End point timeframe

Week 104

End point values	4 mg Bari to 4 mg Bari LTE Substudy with IGA 0, 1 at Week 52	4 mg Bari to 2 mg Bari LTE Substudy with IGA 0, 1 at Week 52	2 mg Bari to 2 mg Bari LTE Substudy with IGA 0, 1 at Week 52	2 mg Bari to 1 mg Bari LTE Substudy with IGA 0, 1 at Week 52
Number of subjects analysed	10	9	10	9
Units: Percentage of participants
number (confidence interval 95%)	50 (23.7 to 76.3)	33.3 (12.1 to 64.6)	90.0 (59.6 to 98.2)	22.2 (6.3 to 54.7)

No statistical analyses for this end point

Secondary: Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed at Week 68 Participants Not Entered Into Substudy (All Participants)

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End point title

Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed at Week 68 Participants Not Entered Into Substudy (All Participants)

End point description

The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification. All missing values were imputed using mLOCF. APD: Participants who received at least one study medication Week 52 to Week 200 in Study JAIN, and were Responders (IGA 0 or 1) and Partial Responders (IGA 2) at Week 52 but were not eligible for downtitration substudy (i.e. had study drug interrupted at Week 52, or had received high or ultra-high potency TCS in the previous 14 days). Additionally, those participants who did not met study discontinuation criteria and continued will be considered in the analysis set.

End point type

Secondary

End point timeframe

Week 68

End point values	LTE 4 mg Baricitinib (Responders/Partial Responders)	LTE 2 mg Baricitinib (Responders/Partial Responders)	LTE 1 mg Baricitinib (Responders/Partial Responders)	LTE Placebo (Responders/Partial Responders)
Number of subjects analysed	7	22	34	29
Units: Percentage of participants
number (confidence interval 95%)	100 (64.6 to 100)	86.4 (66.7 to 95.3)	100 (89.8 to 100)	93.1 (78.0 to 98.1)

No statistical analyses for this end point

Secondary: Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed at Week 104 Participants Not Entered Into Substudy (All Participants)

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End point title

Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed at Week 104 Participants Not Entered Into Substudy (All Participants)

End point description

The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification. All missing values were imputed using mLOCF. APD: Participants who received at least one study medication Week 52 to Week 200 in Study JAIN, and were Responders (IGA 0 or 1) and Partial Responders (IGA 2) at Week 52 but were not eligible for downtitration substudy (i.e. had study drug interrupted at Week 52, or had received high or ultra-high potency TCS in the previous 14 days). Additionally, those participants who did not met study discontinuation criteria and continued will be considered in the analysis set.

End point type

Secondary

End point timeframe

Week 104

End point values	LTE 4 mg Baricitinib (Responders/Partial Responders)	LTE 2 mg Baricitinib (Responders/Partial Responders)	LTE 1 mg Baricitinib (Responders/Partial Responders)	LTE Placebo (Responders/Partial Responders)
Number of subjects analysed	7	22	34	29
Units: Percentage of participants
number (confidence interval 95%)	100 (64.6 to 100)	86.4 (66.7 to 95.3)	97.1 (85.1 to 99.5)	93.1 (78.0 to 98.1)

No statistical analyses for this end point

Secondary: Percentage of Participants With a Response of IGA 0 or 1 Assessed at Week 68 - Participants Not Entered Into Substudy (All Participants)

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End point title

Percentage of Participants With a Response of IGA 0 or 1 Assessed at Week 68 - Participants Not Entered Into Substudy (All Participants)

End point description

The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification. All missing values were imputed using mLOCF. APD: Participants who received at least one study medication Week 52 to Week 200 in Study JAIN, and were Responders (IGA 0 or 1) and Partial Responders (IGA 2) at Week 52 but were not eligible for downtitration substudy (i.e. had study drug interrupted at Week 52, or had received high or ultra-high potency TCS in the previous 14 days). Additionally, those participants who did not met study discontinuation criteria and continued will be considered in the analysis set.

End point type

Secondary

End point timeframe

Week 68

End point values	LTE 4 mg Baricitinib (Responders/Partial Responders)	LTE 2 mg Baricitinib (Responders/Partial Responders)	LTE 1 mg Baricitinib (Responders/Partial Responders)	LTE Placebo (Responders/Partial Responders)
Number of subjects analysed	7	22	34	29
Units: Percentage of participants
number (confidence interval 95%)	14.3 (2.6 to 51.3)	50.0 (30.7 to 69.3)	47.1 (31.5 to 63.3)	51.7 (34.4 to 68.6)

No statistical analyses for this end point

Secondary: Percentage of Participants With a Response of IGA 0 or 1 Assessed at Week 104 - Participants Not Entered into Substudy (All Participants)

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End point title

Percentage of Participants With a Response of IGA 0 or 1 Assessed at Week 104 - Participants Not Entered into Substudy (All Participants)

End point description

The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification. All missing values were imputed using mLOCF. APD: Participants who received at least one study medication Week 52 to Week 200 in Study JAIN, and were Responders (IGA 0 or 1) and Partial Responders (IGA 2) at Week 52 but were not eligible for downtitration substudy (i.e. had study drug interrupted at Week 52, or had received high or ultra-high potency TCS in the previous 14 days). Additionally, those participants who did not met study discontinuation criteria and continued will be considered in the analysis set.

End point type

Secondary

End point timeframe

Week 104

End point values	LTE 4 mg Baricitinib (Responders/Partial Responders)	LTE 2 mg Baricitinib (Responders/Partial Responders)	LTE 1 mg Baricitinib (Responders/Partial Responders)	LTE Placebo (Responders/Partial Responders)
Number of subjects analysed	7	22	34	29
Units: Percentage of participants
number (confidence interval 95%)	42.9 (15.8 to 75.0)	50.0 (30.7 to 69.3)	47.1 (31.5 to 63.3)	48.3 (31.4 to 65.6)

No statistical analyses for this end point

Secondary: Percentage of Participants With A Response of EASI75 Assessed at Week 68 - Participants Not Entered Into Substudy (All Participants)

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End point title

Percentage of Participants With A Response of EASI75 Assessed at Week 68 - Participants Not Entered Into Substudy (All Participants)

End point description

The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 (no disease) to 72 (severe disease). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score. APD: Participants who received at least one study medication Week 52 to Week 200 in Study JAIN, and were Responders (IGA 0 or 1) and Partial Responders (IGA 2) at Week 52 but were not eligible for downtitration substudy.

End point type

Secondary

End point timeframe

Week 68

End point values	LTE 4 mg Baricitinib (Responders/Partial Responders)	LTE 2 mg Baricitinib (Responders/Partial Responders)	LTE 1 mg Baricitinib (Responders/Partial Responders)	LTE Placebo (Responders/Partial Responders)
Number of subjects analysed	7	22	34	29
Units: Percentage of participants
number (confidence interval 95%)	57.1 (25.0 to 84.2)	63.6 (43.0 to 80.3)	76.5 (60.0 to 87.6)	62.1 (44.0 to 77.3)

No statistical analyses for this end point

Secondary: Percentage of Participants With A Response of EASI75 Assessed at Week 104 - Participants Not Entered Into Substudy (All Participants)

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End point title

Percentage of Participants With A Response of EASI75 Assessed at Week 104 - Participants Not Entered Into Substudy (All Participants)

End point description

The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 (no disease) to 72 (severe disease). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score. APD: Participants who received at least one study medication Week 52 to Week 200 in Study JAIN, and were Responders (IGA 0 or 1) and Partial Responders (IGA 2) at Week 52 but were not eligible for downtitration substudy.

End point type

Secondary

End point timeframe

Week 104

End point values	LTE 4 mg Baricitinib (Responders/Partial Responders)	LTE 2 mg Baricitinib (Responders/Partial Responders)	LTE 1 mg Baricitinib (Responders/Partial Responders)	LTE Placebo (Responders/Partial Responders)
Number of subjects analysed	7	22	34	29
Units: Percentage of participants
number (confidence interval 95%)	85.7 (48.7 to 97.4)	68.2 (47.3 to 83.6)	70.6 (53.8 to 83.2)	72.4 (54.3 to 85.3)

No statistical analyses for this end point

Secondary: Time to Retreatment (Time to IGA ≥3) Randomized Downtitration (All Patients Entering the Substudy)

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End point title

Time to Retreatment (Time to IGA ≥3) Randomized Downtitration (All Patients Entering the Substudy)

End point description

Participants who entered the Substudy and relapsed with an IGA ≥3. APD: Participants who received at least one study medication during Week 52 to Week 200 in Study JAIN, entered the downtitration substudy and experienced relapse from Week 52 up to Week 200. Additionally, those participants who did not meet study discontinuation criteria and continued will be considered in the analysis set.

End point type

Secondary

End point timeframe

Week 52 Up to Week 200

End point values	4-mg Bari to 4-mg Bari to 4-mg Bari	4 mg Bari to 2 mg Bari to 4 mg Bari	2 mg Bari to 2 mg Bari to 2 mg Bari	2 mg Bari to 1 mg Bari to 2 mg Bari
Number of subjects analysed	5 ^[27]	11	15	20
Units: Days
median (full range (min-max))	218 (29 to 9999)	79 (28 to 359)	68 (28 to 364)	71 (29 to 225)

Notes
[27] - Upper Confidence Level (CI) not estimable due to censoring.

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Baseline up to Week 200

Adverse event reporting additional description

All randomized participants who received at least 1 dose of investigational product and who did not discontinue from the study for the reason 'Lost to Follow-up' at the first postbaseline visit. Gender specific events occurring only in male or female participants have had the number of participants At Risk adjusted accordingly.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

25.1

Reporting group title

Placebo

Reporting group description

Placebo administered orally once daily in combination with topical corticosteroids. Additional Placebo administered orally to maintain the blind.

Reporting group title

2 mg Baricitinib

Reporting group description

2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Reporting group title

4 mg Baricitinib

Reporting group description

4 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Reporting group title

LTE Substudy 2 mg Baricitinib to 1 mg Baricitinib

Reporting group description

Long Term Extension (LTE) Substudy 2mg Baricitinib to 1mg Baricitinib (Responders/Partial Responders) 2 mg Baricitinib rerandomized to 1 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Reporting group title

LTE Substudy 2 mg Baricitinib to 2 mg Baricitinib

Reporting group description

Reporting group title

LTE Substudy 4 mg Baricitinib to 2 mg Baricitinib

Reporting group description

Reporting group title

Long Term Extension Substudy 4mg to 4mg

Reporting group description

4 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Reporting group title

LTE Placebo (Responders/Partial Responders)

Reporting group description

LTE Placebo (Responders/Partial Responders) - Did Not Enter Substudy Placebo administered orally once daily (continued previous dose) in combination with topical corticosteroids. Additional placebo administered orally to maintain the blind.

Reporting group title

LTE 1 mg Baricitinib (Responders/Partial Responders)

Reporting group description

LTE 1 mg Baricitinib (Responders/Partial Responders) - Did Not Enter Substudy 1 mg Baricitinib administered orally once daily (continued previous dose) in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Reporting group title

LTE 2 mg Baricitinib (Responders/Partial Responders)

Reporting group description

Reporting group title

LTE 4 mg Baricitinib (Responders/Partial Responders)

Reporting group description

LTE 4 mg Baricitinib (Responders/Partial Responders) - Did Not Enter Substudy 4 mg Baricitinib administered orally once daily (continued previous dose) in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Reporting group title

LTE Placebo to 2 mg Baricitinib (Non-responders)

Reporting group description

Reporting group title

LTE Placebo to 4 mg Baricitinib (Non-responders)

Reporting group description

LTE Placebo to 4 mg Baricitinib (Non-responders) - Did Not Enter Substudy Placebo rerandomized to 4 mg Baricitinib administered orally once daily (continued previous dose) in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Reporting group title

LTE 1 mg Baricitinib to 2 mg Baricitinib (Non-responders)

Reporting group description

Reporting group title

LLTE 1 mg Baricitinib to 4 mg Baricitinib (Non-responders)

Reporting group description

LTE 1 mg Baricitinib to 4 mg Baricitinib (Non-responders) - Did Not Enter Substudy 1 mg Baricitinib rerandomized to 4 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Reporting group title

LTE 2 mg Baricitinib to 2 mg Baricitinib (Non-responders)

Reporting group description

LTE 2 mg Baricitinib to 2 mg Baricitinib (Non-responders) - Did Not Enter Substudy 2 mg Baricitinib rerandomized to 2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Reporting group title

LTE 2 mg Baricitinib to 4 mg Baricitinib (Non-responders)

Reporting group description

Reporting group title

LTE 4 mg Baricitinib (Non-responders)

Reporting group description

LTE 4 mg Baricitinib (Non-responders) - Did Not Enter Substudy 4 mg administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Reporting group title

1mg Baricitinib DBT

Reporting group description

1 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Placebo

2 mg Baricitinib

4 mg Baricitinib

LTE Substudy 2 mg Baricitinib to 1 mg Baricitinib

LTE Substudy 2 mg Baricitinib to 2 mg Baricitinib

LTE Substudy 4 mg Baricitinib to 2 mg Baricitinib

Long Term Extension Substudy 4mg to 4mg

LTE Placebo (Responders/Partial Responders)

LTE 1 mg Baricitinib (Responders/Partial Responders)

LTE 2 mg Baricitinib (Responders/Partial Responders)

LTE 4 mg Baricitinib (Responders/Partial Responders)

LTE Placebo to 2 mg Baricitinib (Non-responders)

LTE Placebo to 4 mg Baricitinib (Non-responders)

LTE 1 mg Baricitinib to 2 mg Baricitinib (Non-responders)

LLTE 1 mg Baricitinib to 4 mg Baricitinib (Non-responders)

LTE 2 mg Baricitinib to 2 mg Baricitinib (Non-responders)

LTE 2 mg Baricitinib to 4 mg Baricitinib (Non-responders)

LTE 4 mg Baricitinib (Non-responders)

1mg Baricitinib DBT

Total subjects affected by serious adverse events

subjects affected / exposed

5 / 93 (5.38%)

9 / 184 (4.89%)

10 / 92 (10.87%)

3 / 24 (12.50%)

4 / 25 (16.00%)

3 / 16 (18.75%)

1 / 29 (3.45%)

1 / 34 (2.94%)

1 / 22 (4.55%)

2 / 7 (28.57%)

1 / 11 (9.09%)

2 / 12 (16.67%)

2 / 13 (15.38%)

3 / 14 (21.43%)

3 / 27 (11.11%)

5 / 26 (19.23%)

4 / 24 (16.67%)

7 / 93 (7.53%)

number of deaths (all causes)

number of deaths resulting from adverse events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

adenocarcinoma of colon

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

1 / 27 (3.70%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

bowen's disease

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

1 / 93 (1.08%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

breast cancer

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

1 / 93 (1.08%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

haemangioma

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

1 / 25 (4.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

prostate cancer

alternative dictionary used: MedDRA 25.1

subjects affected / exposed ^[1]

0 / 49 (0.00%)

0 / 132 (0.00%)

0 / 57 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 15 (0.00%)

0 / 21 (0.00%)

0 / 14 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

1 / 8 (12.50%)

0 / 20 (0.00%)

0 / 17 (0.00%)

0 / 58 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

squamous cell carcinoma

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

1 / 16 (6.25%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

hypertensive crisis

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

1 / 16 (6.25%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

peripheral arterial occlusive disease

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

1 / 16 (6.25%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General disorders and administration site conditions

soft tissue inflammation

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

1 / 92 (1.09%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

asthma

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

1 / 93 (1.08%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Psychiatric disorders

adjustment disorder

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

1 / 26 (3.85%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

suicidal ideation

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

1 / 27 (3.70%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Product issues

device dislocation

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

1 / 24 (4.17%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

ankle fracture

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

1 / 25 (4.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

fall

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

1 / 26 (3.85%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

forearm fracture

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

1 / 14 (7.14%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

injury corneal

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

1 / 13 (7.69%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ligament rupture

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

1 / 92 (1.09%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

1 / 16 (6.25%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

meniscus injury

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

1 / 16 (6.25%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

mouth injury

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

1 / 26 (3.85%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

scapula fracture

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

1 / 24 (4.17%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

tendon rupture

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

1 / 26 (3.85%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

acute myocardial infarction

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

1 / 184 (0.54%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cardiac arrest

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

1 / 24 (4.17%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

coronary artery disease

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

1 / 184 (0.54%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

myocardial ischaemia

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

1 / 26 (3.85%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

brain oedema

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

1 / 24 (4.17%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cerebral haemorrhage

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

1 / 24 (4.17%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

embolic stroke

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

1 / 24 (4.17%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ischaemic stroke

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

1 / 34 (2.94%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

transient ischaemic attack

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

1 / 34 (2.94%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

tremor

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

1 / 184 (0.54%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Eye disorders

conjunctivitis allergic

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

1 / 92 (1.09%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

corneal erosion

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

1 / 92 (1.09%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

retinal detachment

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

1 / 13 (7.69%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Skin and subcutaneous tissue disorders

dermatitis atopic

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

2 / 93 (2.15%)

1 / 184 (0.54%)

2 / 92 (2.17%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

1 / 22 (4.55%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

1 / 27 (3.70%)

0 / 26 (0.00%)

1 / 24 (4.17%)

2 / 93 (2.15%)

occurrences causally related to treatment / all

1 / 2

1 / 1

1 / 2

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

0 / 1

0 / 2

deaths causally related to treatment / all

0 / 0

dyshidrotic eczema

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

1 / 184 (0.54%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

eczema

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

1 / 92 (1.09%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

hypertrophic scar

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

1 / 26 (3.85%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

nephrolithiasis

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

1 / 25 (4.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

bursitis

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

2 / 93 (2.15%)

occurrences causally related to treatment / all

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

flank pain

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

1 / 16 (6.25%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

intervertebral disc degeneration

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

1 / 93 (1.08%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

spinal stenosis

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

1 / 16 (6.25%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

tenosynovitis

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

1 / 7 (14.29%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

anal abscess

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

1 / 16 (6.25%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cellulitis

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

1 / 93 (1.08%)

1 / 184 (0.54%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

1 / 7 (14.29%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

1 / 26 (3.85%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

covid-19

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

1 / 29 (3.45%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

1 / 11 (9.09%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

1 / 27 (3.70%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

corneal abscess

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

1 / 93 (1.08%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

eczema herpeticum

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

1 / 184 (0.54%)

0 / 92 (0.00%)

0 / 24 (0.00%)

1 / 25 (4.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

1 / 14 (7.14%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

erysipelas

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

1 / 93 (1.08%)

0 / 184 (0.00%)

1 / 92 (1.09%)

0 / 24 (0.00%)

0 / 25 (0.00%)

1 / 16 (6.25%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

1 / 12 (8.33%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 2

0 / 0

1 / 1

0 / 0

0 / 1

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

fracture infection

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

1 / 14 (7.14%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

furuncle

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

1 / 184 (0.54%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

gastroenteritis

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

1 / 16 (6.25%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

papilloma viral infection

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

1 / 92 (1.09%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ophthalmic herpes simplex

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

1 / 24 (4.17%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

1 / 14 (7.14%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

perichondritis

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

1 / 12 (8.33%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

periorbital cellulitis

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

1 / 24 (4.17%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

peritonitis

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

1 / 7 (14.29%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pneumonia bacterial

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

1 / 184 (0.54%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pneumonia

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

1 / 184 (0.54%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

1 / 12 (8.33%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

postoperative wound infection

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

1 / 93 (1.08%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

pyelitis

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

1 / 92 (1.09%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

sepsis

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

0 / 92 (0.00%)

1 / 24 (4.17%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

staphylococcal infection

alternative dictionary used: MedDRA 25.1

subjects affected / exposed

0 / 93 (0.00%)

0 / 184 (0.00%)

1 / 92 (1.09%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 16 (0.00%)

0 / 29 (0.00%)

0 / 34 (0.00%)

0 / 22 (0.00%)

0 / 7 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

0 / 27 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 93 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Gender specific events occurring only in male or female participants have had the number of participants At Risk adjusted accordingly.

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

Non-serious adverse events	Placebo	2 mg Baricitinib	4 mg Baricitinib	LTE Substudy 2 mg Baricitinib to 1 mg Baricitinib	LTE Substudy 2 mg Baricitinib to 2 mg Baricitinib	LTE Substudy 4 mg Baricitinib to 2 mg Baricitinib	Long Term Extension Substudy 4mg to 4mg	LTE Placebo (Responders/Partial Responders)	LTE 1 mg Baricitinib (Responders/Partial Responders)	LTE 2 mg Baricitinib (Responders/Partial Responders)	LTE 4 mg Baricitinib (Responders/Partial Responders)	LTE Placebo to 2 mg Baricitinib (Non-responders)	LTE Placebo to 4 mg Baricitinib (Non-responders)	LTE 1 mg Baricitinib to 2 mg Baricitinib (Non-responders)	LLTE 1 mg Baricitinib to 4 mg Baricitinib (Non-responders)	LTE 2 mg Baricitinib to 2 mg Baricitinib (Non-responders)	LTE 2 mg Baricitinib to 4 mg Baricitinib (Non-responders)	LTE 4 mg Baricitinib (Non-responders)	1mg Baricitinib DBT
Total subjects affected by non serious adverse events
subjects affected / exposed	50 / 93 (53.76%)	130 / 184 (70.65%)	75 / 92 (81.52%)	17 / 24 (70.83%)	16 / 25 (64.00%)	13 / 16 (81.25%)	16 / 16 (100.00%)	16 / 29 (55.17%)	25 / 34 (73.53%)	16 / 22 (72.73%)	7 / 7 (100.00%)	6 / 11 (54.55%)	10 / 12 (83.33%)	11 / 13 (84.62%)	13 / 14 (92.86%)	18 / 27 (66.67%)	18 / 26 (69.23%)	16 / 24 (66.67%)	63 / 93 (67.74%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
anogenital warts
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
hepatic adenoma
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
seborrhoeic keratosis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
skin papilloma
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	4 / 184 (2.17%)	2 / 92 (2.17%)	1 / 24 (4.17%)	0 / 25 (0.00%)	0 / 16 (0.00%)	2 / 16 (12.50%)	1 / 29 (3.45%)	0 / 34 (0.00%)	1 / 22 (4.55%)	1 / 7 (14.29%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	4	2	3	0	0	2	1	0	1	1	0	0	1	0	0	0	0	0
Vascular disorders
hypertension
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 93 (1.08%)	5 / 184 (2.72%)	3 / 92 (3.26%)	0 / 24 (0.00%)	1 / 25 (4.00%)	1 / 16 (6.25%)	2 / 16 (12.50%)	2 / 29 (6.90%)	0 / 34 (0.00%)	1 / 22 (4.55%)	2 / 7 (28.57%)	1 / 11 (9.09%)	0 / 12 (0.00%)	1 / 13 (7.69%)	1 / 14 (7.14%)	1 / 27 (3.70%)	0 / 26 (0.00%)	0 / 24 (0.00%)	3 / 93 (3.23%)
occurrences all number	1	5	3	0	3	1	2	2	0	1	2	1	0	1	1	1	0	0	3
orthostatic hypotension
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
peripheral arterial occlusive disease
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Surgical and medical procedures
abscess drainage
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	2 / 24 (8.33%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0
dental implantation
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	3 / 184 (1.63%)	0 / 92 (0.00%)	0 / 24 (0.00%)	1 / 25 (4.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	3	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0
intrauterine contraception
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 11 (9.09%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
prostatectomy
alternative dictionary used: MedDRA 25.1
subjects affected / exposed ^[2]	0 / 49 (0.00%)	0 / 132 (0.00%)	0 / 57 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 15 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 58 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
retinopexy
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
shoulder operation
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0
tooth extraction
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	2 / 184 (1.09%)	2 / 92 (2.17%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	1 / 29 (3.45%)	1 / 34 (2.94%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	2 / 26 (7.69%)	2 / 24 (8.33%)	0 / 93 (0.00%)
occurrences all number	0	2	2	0	0	1	0	1	1	0	0	0	0	0	0	0	2	2	0
tooth restoration
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
uterine polypectomy
alternative dictionary used: MedDRA 25.1
subjects affected / exposed ^[3]	0 / 44 (0.00%)	0 / 52 (0.00%)	0 / 35 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 14 (0.00%)	0 / 13 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 35 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
vasectomy
alternative dictionary used: MedDRA 25.1
subjects affected / exposed ^[4]	0 / 49 (0.00%)	0 / 132 (0.00%)	0 / 57 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 10 (10.00%)	0 / 8 (0.00%)	0 / 15 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 58 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
General disorders and administration site conditions
asthenia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 93 (1.08%)	3 / 184 (1.63%)	1 / 92 (1.09%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	1 / 34 (2.94%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	1 / 93 (1.08%)
occurrences all number	1	3	1	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	1
fatigue
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	3 / 93 (3.23%)	2 / 184 (1.09%)	3 / 92 (3.26%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	3 / 93 (3.23%)
occurrences all number	4	2	3	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	3
implant site pain
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
influenza like illness
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	3 / 93 (3.23%)	6 / 184 (3.26%)	2 / 92 (2.17%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	2 / 16 (12.50%)	1 / 29 (3.45%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)	0 / 27 (0.00%)	1 / 26 (3.85%)	1 / 24 (4.17%)	0 / 93 (0.00%)
occurrences all number	3	6	3	0	0	0	2	1	0	0	0	0	0	0	1	0	1	1	0
pyrexia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	3 / 184 (1.63%)	0 / 92 (0.00%)	1 / 24 (4.17%)	0 / 25 (0.00%)	2 / 16 (12.50%)	0 / 16 (0.00%)	0 / 29 (0.00%)	1 / 34 (2.94%)	1 / 22 (4.55%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	2 / 13 (15.38%)	1 / 14 (7.14%)	1 / 27 (3.70%)	1 / 26 (3.85%)	1 / 24 (4.17%)	3 / 93 (3.23%)
occurrences all number	0	3	0	1	0	2	0	0	1	1	0	0	0	3	1	3	1	1	4
swelling face
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 93 (1.08%)	1 / 184 (0.54%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Reproductive system and breast disorders
cervical dysplasia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed ^[5]	0 / 44 (0.00%)	0 / 52 (0.00%)	0 / 35 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 14 (0.00%)	0 / 13 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 35 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
dysmenorrhoea
alternative dictionary used: MedDRA 25.1
subjects affected / exposed ^[6]	0 / 44 (0.00%)	0 / 52 (0.00%)	0 / 35 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 14 (0.00%)	3 / 13 (23.08%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	2 / 35 (5.71%)
occurrences all number	0	0	0	0	0	0	0	0	9	0	0	0	0	0	0	0	0	1	3
ovarian cyst
alternative dictionary used: MedDRA 25.1
subjects affected / exposed ^[7]	0 / 44 (0.00%)	0 / 52 (0.00%)	0 / 35 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 14 (0.00%)	1 / 13 (7.69%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 35 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
prostatitis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed ^[8]	0 / 49 (0.00%)	0 / 132 (0.00%)	0 / 57 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 15 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 58 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
vaginal discharge
alternative dictionary used: MedDRA 25.1
subjects affected / exposed ^[9]	0 / 44 (0.00%)	0 / 52 (0.00%)	0 / 35 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 14 (0.00%)	0 / 13 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 35 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
asthmatic crisis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 93 (1.08%)	1 / 184 (0.54%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	2	2	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
asthma
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	4 / 93 (4.30%)	3 / 184 (1.63%)	1 / 92 (1.09%)	0 / 24 (0.00%)	2 / 25 (8.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	1 / 22 (4.55%)	1 / 7 (14.29%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	2 / 27 (7.41%)	0 / 26 (0.00%)	0 / 24 (0.00%)	1 / 93 (1.08%)
occurrences all number	4	4	2	0	2	0	0	0	0	1	1	0	0	0	0	2	0	0	2
cough
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 93 (1.08%)	9 / 184 (4.89%)	2 / 92 (2.17%)	0 / 24 (0.00%)	1 / 25 (4.00%)	1 / 16 (6.25%)	2 / 16 (12.50%)	1 / 29 (3.45%)	1 / 34 (2.94%)	1 / 22 (4.55%)	1 / 7 (14.29%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	2 / 93 (2.15%)
occurrences all number	1	10	2	0	1	1	2	2	1	1	1	0	0	0	0	0	0	0	2
nasal congestion
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	1 / 92 (1.09%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	1 / 24 (4.17%)	2 / 93 (2.15%)
occurrences all number	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1	2
oropharyngeal pain
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 93 (1.08%)	7 / 184 (3.80%)	3 / 92 (3.26%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	1 / 29 (3.45%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	1 / 14 (7.14%)	1 / 27 (3.70%)	0 / 26 (0.00%)	1 / 24 (4.17%)	7 / 93 (7.53%)
occurrences all number	1	7	3	0	0	1	0	2	0	0	0	0	0	1	1	1	0	1	10
rhinitis allergic
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 93 (1.08%)	0 / 184 (0.00%)	0 / 92 (0.00%)	2 / 24 (8.33%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	1 / 93 (1.08%)
occurrences all number	1	0	0	3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Psychiatric disorders
anxiety
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	1 / 92 (1.09%)	0 / 24 (0.00%)	1 / 25 (4.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	1	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0
depressed mood
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 93 (1.08%)	1 / 184 (0.54%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	2 / 34 (5.88%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0
insomnia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	2 / 93 (2.15%)	3 / 184 (1.63%)	2 / 92 (2.17%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 29 (3.45%)	1 / 34 (2.94%)	1 / 22 (4.55%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)	1 / 27 (3.70%)	1 / 26 (3.85%)	0 / 24 (0.00%)	2 / 93 (2.15%)
occurrences all number	2	4	2	0	0	0	0	1	2	1	0	0	0	1	0	1	1	0	3
premature ejaculation
alternative dictionary used: MedDRA 25.1
subjects affected / exposed ^[10]	0 / 49 (0.00%)	0 / 132 (0.00%)	0 / 57 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 15 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 58 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
stress
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	1 / 184 (0.54%)	1 / 92 (1.09%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	0 / 14 (0.00%)	1 / 27 (3.70%)	0 / 26 (0.00%)	0 / 24 (0.00%)	1 / 93 (1.08%)
occurrences all number	0	1	1	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	1
somatic symptom disorder
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Investigations
alanine aminotransferase increased
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	2 / 93 (2.15%)	5 / 184 (2.72%)	1 / 92 (1.09%)	1 / 24 (4.17%)	0 / 25 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 29 (0.00%)	1 / 34 (2.94%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	2 / 24 (8.33%)	1 / 93 (1.08%)
occurrences all number	2	5	1	2	0	1	0	0	2	0	0	0	0	0	0	0	0	2	1
arthroscopy
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 29 (0.00%)	1 / 34 (2.94%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	1 / 93 (1.08%)
occurrences all number	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0	1
aspartate aminotransferase increased
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 93 (1.08%)	1 / 184 (0.54%)	2 / 92 (2.17%)	1 / 24 (4.17%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	1 / 34 (2.94%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	2 / 27 (7.41%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	1	1	2	1	0	0	0	0	1	0	0	0	0	0	0	2	0	0	0
blood creatine phosphokinase increased
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	2 / 93 (2.15%)	3 / 184 (1.63%)	2 / 92 (2.17%)	2 / 24 (8.33%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	1 / 34 (2.94%)	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	2 / 27 (7.41%)	0 / 26 (0.00%)	1 / 24 (4.17%)	3 / 93 (3.23%)
occurrences all number	2	3	2	2	0	0	0	0	1	0	1	0	0	0	0	2	0	1	3
blood alkaline phosphatase increased
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 93 (1.08%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	1	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
blood creatinine increased
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	2 / 93 (2.15%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	2	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
blood triglycerides increased
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 93 (1.08%)	1 / 184 (0.54%)	1 / 92 (1.09%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	1 / 26 (3.85%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	1	1	1	0	0	0	1	0	0	0	0	0	0	0	0	0	2	0	0
colonoscopy
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	1 / 184 (0.54%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	1	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
lymphocyte count decreased
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	2 / 92 (2.17%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	1 / 27 (3.70%)	1 / 26 (3.85%)	1 / 24 (4.17%)	0 / 93 (0.00%)
occurrences all number	0	0	2	0	0	1	0	0	0	0	0	0	0	0	0	1	1	1	0
prostatic specific antigen increased
alternative dictionary used: MedDRA 25.1
subjects affected / exposed ^[11]	0 / 49 (0.00%)	0 / 132 (0.00%)	0 / 57 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 15 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 58 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
sars-cov-2 test positive
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	1 / 34 (2.94%)	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	1	0	0	0	1	0	0	0	0
sars-cov-2 antibody test positive
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
weight increased
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 93 (1.08%)	2 / 184 (1.09%)	2 / 92 (2.17%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	1 / 27 (3.70%)	0 / 26 (0.00%)	0 / 24 (0.00%)	1 / 93 (1.08%)
occurrences all number	1	2	2	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	1
Injury, poisoning and procedural complications
ligament rupture
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	1 / 92 (1.09%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	1 / 29 (3.45%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	1	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0
ligament sprain
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	2 / 92 (2.17%)	0 / 24 (0.00%)	1 / 25 (4.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)	0 / 27 (0.00%)	1 / 26 (3.85%)	0 / 24 (0.00%)	2 / 93 (2.15%)
occurrences all number	0	0	2	0	1	0	0	0	0	0	0	0	0	1	0	0	1	0	3
meniscus injury
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	2 / 184 (1.09%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	2 / 16 (12.50%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	2	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0
post vaccination syndrome
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	2 / 16 (12.50%)	0 / 16 (0.00%)	2 / 29 (6.90%)	2 / 34 (5.88%)	2 / 22 (9.09%)	0 / 7 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	2 / 26 (7.69%)	2 / 24 (8.33%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	2	0	2	2	2	0	0	2	0	0	0	3	5	0
procedural pain
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	1 / 24 (4.17%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
rib fracture
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	2 / 26 (7.69%)	1 / 24 (4.17%)	2 / 93 (2.15%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	1	2
tendon rupture
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	1 / 26 (3.85%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0
tooth fracture
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	3 / 184 (1.63%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	3	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Cardiac disorders
angina pectoris
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	2 / 184 (1.09%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Nervous system disorders
dizziness
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	2 / 184 (1.09%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	1 / 29 (3.45%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	2	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0
headache
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	8 / 93 (8.60%)	14 / 184 (7.61%)	10 / 92 (10.87%)	1 / 24 (4.17%)	5 / 25 (20.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	1 / 29 (3.45%)	2 / 34 (5.88%)	1 / 22 (4.55%)	1 / 7 (14.29%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	0 / 14 (0.00%)	1 / 27 (3.70%)	2 / 26 (7.69%)	1 / 24 (4.17%)	8 / 93 (8.60%)
occurrences all number	10	17	13	2	5	1	0	1	2	1	1	0	1	0	0	1	2	3	15
migraine
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 93 (1.08%)	2 / 184 (1.09%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	1 / 34 (2.94%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	2 / 12 (16.67%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	1 / 93 (1.08%)
occurrences all number	1	2	0	0	0	0	0	0	5	0	0	0	3	0	0	0	0	0	1
neuralgia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 93 (1.08%)	0 / 184 (0.00%)	1 / 92 (1.09%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	1 / 26 (3.85%)	0 / 24 (0.00%)	1 / 93 (1.08%)
occurrences all number	1	0	1	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	1
paraesthesia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	1 / 184 (0.54%)	0 / 92 (0.00%)	1 / 24 (4.17%)	0 / 25 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	1	0	1	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0
post herpetic neuralgia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	1 / 92 (1.09%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
tension headache
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 93 (1.08%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Blood and lymphatic system disorders
anaemia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	1 / 22 (4.55%)	0 / 7 (0.00%)	1 / 11 (9.09%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0
eosinophilia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	1 / 92 (1.09%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	1	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0
iron deficiency anaemia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 93 (1.08%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	1 / 26 (3.85%)	1 / 24 (4.17%)	0 / 93 (0.00%)
occurrences all number	1	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	1	1	0
leukopenia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 93 (1.08%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	1 / 93 (1.08%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1
lymphadenopathy
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	1 / 184 (0.54%)	1 / 92 (1.09%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 29 (0.00%)	0 / 34 (0.00%)	1 / 22 (4.55%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	1 / 93 (1.08%)
occurrences all number	0	1	1	0	0	0	1	0	0	1	0	0	0	0	1	0	0	0	1
lymphopenia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	1 / 184 (0.54%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 29 (0.00%)	0 / 34 (0.00%)	1 / 22 (4.55%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	1 / 93 (1.08%)
occurrences all number	0	2	0	0	0	0	1	0	0	1	0	0	0	0	1	0	0	0	2
neutrophilia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
thrombocytosis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	1 / 34 (2.94%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0	0
Ear and labyrinth disorders
deafness
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	1 / 93 (1.08%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1
ear pain
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 93 (1.08%)	0 / 184 (0.00%)	1 / 92 (1.09%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	1 / 24 (4.17%)	0 / 93 (0.00%)
occurrences all number	1	0	1	0	0	2	0	0	0	0	0	0	0	0	0	0	0	1	0
vertigo
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 29 (3.45%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0
Eye disorders
blepharitis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 93 (1.08%)	4 / 184 (2.17%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	1	4	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
conjunctival irritation
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	1 / 184 (0.54%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
conjunctivitis allergic
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	3 / 93 (3.23%)	3 / 184 (1.63%)	0 / 92 (0.00%)	0 / 24 (0.00%)	1 / 25 (4.00%)	1 / 16 (6.25%)	1 / 16 (6.25%)	4 / 29 (13.79%)	1 / 34 (2.94%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	1 / 14 (7.14%)	1 / 27 (3.70%)	1 / 26 (3.85%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	3	3	0	0	1	1	1	4	1	0	0	0	0	1	1	1	1	0	0
dry eye
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	4 / 93 (4.30%)	0 / 184 (0.00%)	0 / 92 (0.00%)	2 / 24 (8.33%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 11 (9.09%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	4	0	0	2	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
glaucoma
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
keratoconus
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	1 / 92 (1.09%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 16 (6.25%)	1 / 16 (6.25%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	1	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0
lacrimation increased
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
noninfective conjunctivitis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	1 / 92 (1.09%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
retinal detachment
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0
vitreous floaters
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Gastrointestinal disorders
abdominal pain upper
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	3 / 93 (3.23%)	7 / 184 (3.80%)	5 / 92 (5.43%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 29 (0.00%)	1 / 34 (2.94%)	1 / 22 (4.55%)	0 / 7 (0.00%)	0 / 11 (0.00%)	2 / 12 (16.67%)	0 / 13 (0.00%)	0 / 14 (0.00%)	1 / 27 (3.70%)	0 / 26 (0.00%)	0 / 24 (0.00%)	2 / 93 (2.15%)
occurrences all number	3	7	6	0	0	0	1	0	1	2	0	0	2	0	0	1	0	0	3
constipation
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	4 / 184 (2.17%)	0 / 92 (0.00%)	1 / 24 (4.17%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	1 / 93 (1.08%)
occurrences all number	0	4	0	1	0	0	0	0	0	0	0	0	0	2	0	0	0	0	1
dental caries
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	2 / 184 (1.09%)	0 / 92 (0.00%)	1 / 24 (4.17%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	1 / 34 (2.94%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	2	0	1	0	0	0	0	1	0	0	0	1	0	0	0	0	0	0
diarrhoea
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	3 / 93 (3.23%)	9 / 184 (4.89%)	6 / 92 (6.52%)	0 / 24 (0.00%)	1 / 25 (4.00%)	2 / 16 (12.50%)	0 / 16 (0.00%)	1 / 29 (3.45%)	1 / 34 (2.94%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	0 / 14 (0.00%)	1 / 27 (3.70%)	0 / 26 (0.00%)	1 / 24 (4.17%)	2 / 93 (2.15%)
occurrences all number	3	10	6	0	1	2	0	1	1	0	0	0	1	0	0	1	0	1	2
dyspepsia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	2 / 184 (1.09%)	2 / 92 (2.17%)	1 / 24 (4.17%)	0 / 25 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	2 / 93 (2.15%)
occurrences all number	0	2	3	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	3
frequent bowel movements
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	1 / 92 (1.09%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
gastritis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	1 / 92 (1.09%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	1 / 34 (2.94%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	1 / 93 (1.08%)
occurrences all number	0	0	1	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	1
gastrooesophageal reflux disease
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 93 (1.08%)	2 / 184 (1.09%)	0 / 92 (0.00%)	0 / 24 (0.00%)	1 / 25 (4.00%)	1 / 16 (6.25%)	1 / 16 (6.25%)	1 / 29 (3.45%)	1 / 34 (2.94%)	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	1 / 93 (1.08%)
occurrences all number	1	2	0	0	1	1	1	1	1	0	1	0	0	0	0	0	0	0	1
nausea
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	8 / 184 (4.35%)	2 / 92 (2.17%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	1 / 22 (4.55%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	1 / 27 (3.70%)	0 / 26 (0.00%)	0 / 24 (0.00%)	2 / 93 (2.15%)
occurrences all number	0	11	2	0	0	1	0	0	0	1	0	0	0	0	0	1	0	0	2
stomatitis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 11 (9.09%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
toothache
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	1 / 184 (0.54%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	1 / 34 (2.94%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	2 / 24 (8.33%)	0 / 93 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	2	0
Skin and subcutaneous tissue disorders
alopecia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 93 (1.08%)	1 / 184 (0.54%)	1 / 92 (1.09%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	1 / 24 (4.17%)	2 / 93 (2.15%)
occurrences all number	1	1	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	1	2
actinic keratosis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	1 / 184 (0.54%)	1 / 92 (1.09%)	1 / 24 (4.17%)	0 / 25 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 29 (0.00%)	1 / 34 (2.94%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	1	2	1	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0
acne
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	8 / 184 (4.35%)	3 / 92 (3.26%)	1 / 24 (4.17%)	0 / 25 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 29 (0.00%)	3 / 34 (8.82%)	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 11 (9.09%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)	0 / 27 (0.00%)	1 / 26 (3.85%)	1 / 24 (4.17%)	4 / 93 (4.30%)
occurrences all number	0	8	3	1	0	0	1	0	4	0	0	1	0	1	0	0	1	1	5
dermatitis acneiform
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	1 / 25 (4.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0
dermatitis atopic
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	1 / 184 (0.54%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	1	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
dermatitis exfoliative generalised
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	1 / 92 (1.09%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
dermatitis contact
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	2 / 92 (2.17%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	1 / 22 (4.55%)	1 / 7 (14.29%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0
diffuse alopecia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	2 / 184 (1.09%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	1 / 93 (1.08%)
occurrences all number	0	2	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1
dyshidrotic eczema
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	3 / 184 (1.63%)	1 / 92 (1.09%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	2 / 34 (5.88%)	1 / 22 (4.55%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	2 / 93 (2.15%)
occurrences all number	0	4	1	0	0	0	0	0	3	1	0	0	0	0	0	0	0	0	2
hyperhidrosis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	1 / 93 (1.08%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1
milia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
miliaria
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	1 / 25 (4.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0
onycholysis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
rash papular
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
skin disorder
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
skin ulcer
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
urticaria
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	2 / 93 (2.15%)	2 / 184 (1.09%)	2 / 92 (2.17%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	1 / 29 (3.45%)	1 / 34 (2.94%)	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	1 / 27 (3.70%)	0 / 26 (0.00%)	0 / 24 (0.00%)	1 / 93 (1.08%)
occurrences all number	2	2	2	0	0	0	1	1	1	0	1	0	0	0	0	1	0	0	1
Renal and urinary disorders
dysuria
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	3 / 92 (3.26%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	1 / 93 (1.08%)
occurrences all number	0	0	4	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	1
Musculoskeletal and connective tissue disorders
arthralgia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 93 (1.08%)	7 / 184 (3.80%)	5 / 92 (5.43%)	1 / 24 (4.17%)	0 / 25 (0.00%)	2 / 16 (12.50%)	0 / 16 (0.00%)	1 / 29 (3.45%)	2 / 34 (5.88%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	1 / 27 (3.70%)	0 / 26 (0.00%)	0 / 24 (0.00%)	4 / 93 (4.30%)
occurrences all number	1	8	5	1	0	2	0	1	2	0	0	0	0	0	0	1	0	0	4
back pain
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	5 / 93 (5.38%)	6 / 184 (3.26%)	6 / 92 (6.52%)	0 / 24 (0.00%)	1 / 25 (4.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	2 / 29 (6.90%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	1 / 27 (3.70%)	1 / 26 (3.85%)	1 / 24 (4.17%)	6 / 93 (6.45%)
occurrences all number	6	7	9	0	1	0	0	3	0	0	0	0	0	0	0	1	1	1	9
bursitis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	2 / 184 (1.09%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	1 / 27 (3.70%)	0 / 26 (0.00%)	0 / 24 (0.00%)	3 / 93 (3.23%)
occurrences all number	0	2	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	4
muscle contracture
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	1 / 184 (0.54%)	1 / 92 (1.09%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	1 / 93 (1.08%)
occurrences all number	0	1	1	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1
myalgia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 93 (1.08%)	3 / 184 (1.63%)	1 / 92 (1.09%)	2 / 24 (8.33%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	2 / 34 (5.88%)	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 11 (9.09%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	3 / 93 (3.23%)
occurrences all number	1	4	1	2	0	0	0	0	2	0	0	2	0	0	1	0	0	0	4
muscle spasms
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	1 / 184 (0.54%)	0 / 92 (0.00%)	0 / 24 (0.00%)	1 / 25 (4.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 29 (0.00%)	1 / 34 (2.94%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	1	0	0	1	1	0	0	1	0	0	0	0	0	0	0	0	0	0
neck pain
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 93 (1.08%)	2 / 184 (1.09%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	1 / 22 (4.55%)	0 / 7 (0.00%)	1 / 11 (9.09%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	1	2	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0
pain in extremity
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	2 / 93 (2.15%)	5 / 184 (2.72%)	2 / 92 (2.17%)	3 / 24 (12.50%)	0 / 25 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	1 / 29 (3.45%)	1 / 34 (2.94%)	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 11 (9.09%)	1 / 12 (8.33%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	1 / 26 (3.85%)	0 / 24 (0.00%)	2 / 93 (2.15%)
occurrences all number	2	6	2	3	0	0	1	1	1	0	0	2	1	0	0	0	1	0	2
rotator cuff syndrome
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	1 / 25 (4.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	1 / 93 (1.08%)
occurrences all number	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	1
tendon disorder
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
tendonitis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	2 / 184 (1.09%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	0 / 14 (0.00%)	2 / 27 (7.41%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	2	0	0	0	0	1	0	0	0	0	0	1	0	0	2	0	0	0
tenosynovitis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0
Infections and infestations
abscess
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	1 / 93 (1.08%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1
anal abscess
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
bacterial infection
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	1 / 184 (0.54%)	2 / 92 (2.17%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)	0 / 27 (0.00%)	1 / 26 (3.85%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	1	2	0	0	0	0	0	0	0	1	0	0	2	0	0	1	0	0
bronchitis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	2 / 93 (2.15%)	7 / 184 (3.80%)	1 / 92 (1.09%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	3 / 16 (18.75%)	0 / 29 (0.00%)	0 / 34 (0.00%)	1 / 22 (4.55%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)	2 / 27 (7.41%)	0 / 26 (0.00%)	1 / 24 (4.17%)	3 / 93 (3.23%)
occurrences all number	2	9	1	0	0	0	3	0	0	1	0	0	0	0	2	2	0	1	3
candida infection
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	1 / 184 (0.54%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	4	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
covid-19
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	3 / 24 (12.50%)	4 / 25 (16.00%)	1 / 16 (6.25%)	4 / 16 (25.00%)	4 / 29 (13.79%)	6 / 34 (17.65%)	4 / 22 (18.18%)	2 / 7 (28.57%)	1 / 11 (9.09%)	0 / 12 (0.00%)	1 / 13 (7.69%)	3 / 14 (21.43%)	4 / 27 (14.81%)	5 / 26 (19.23%)	4 / 24 (16.67%)	0 / 93 (0.00%)
occurrences all number	0	0	0	3	5	1	4	5	6	4	2	1	0	1	4	5	5	5	0
cellulitis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 93 (1.08%)	2 / 184 (1.09%)	2 / 92 (2.17%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 29 (3.45%)	0 / 34 (0.00%)	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	2 / 26 (7.69%)	1 / 24 (4.17%)	1 / 93 (1.08%)
occurrences all number	3	3	2	0	0	0	0	1	0	0	2	0	0	0	0	0	8	3	1
conjunctivitis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 93 (1.08%)	3 / 184 (1.63%)	5 / 92 (5.43%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 16 (6.25%)	1 / 16 (6.25%)	0 / 29 (0.00%)	1 / 34 (2.94%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	3 / 14 (21.43%)	1 / 27 (3.70%)	0 / 26 (0.00%)	1 / 24 (4.17%)	1 / 93 (1.08%)
occurrences all number	1	4	5	0	0	1	1	0	1	0	0	0	0	0	3	1	0	2	1
cystitis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	1 / 184 (0.54%)	0 / 92 (0.00%)	0 / 24 (0.00%)	1 / 25 (4.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	1 / 34 (2.94%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	1 / 24 (4.17%)	0 / 93 (0.00%)
occurrences all number	0	1	0	0	1	0	0	0	1	0	0	0	1	0	0	0	0	1	0
dermatophytosis of nail
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
dermatitis infected
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 29 (3.45%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0
ear infection
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	9 / 184 (4.89%)	1 / 92 (1.09%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	1 / 29 (3.45%)	0 / 34 (0.00%)	1 / 22 (4.55%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)	1 / 27 (3.70%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	9	1	0	0	0	1	1	0	1	0	0	0	1	0	2	0	0	0
ear infection bacterial
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0
eczema herpeticum
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	2 / 184 (1.09%)	2 / 92 (2.17%)	1 / 24 (4.17%)	2 / 25 (8.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 29 (3.45%)	1 / 34 (2.94%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)	0 / 27 (0.00%)	2 / 26 (7.69%)	2 / 24 (8.33%)	1 / 93 (1.08%)
occurrences all number	0	3	4	1	3	0	0	1	1	0	0	0	0	1	0	0	2	2	1
erysipelas
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 93 (1.08%)	4 / 184 (2.17%)	4 / 92 (4.35%)	1 / 24 (4.17%)	0 / 25 (0.00%)	2 / 16 (12.50%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	1 / 26 (3.85%)	1 / 24 (4.17%)	0 / 93 (0.00%)
occurrences all number	2	5	5	1	0	3	0	0	0	0	0	0	2	0	0	0	1	1	0
folliculitis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	2 / 93 (2.15%)	9 / 184 (4.89%)	0 / 92 (0.00%)	2 / 24 (8.33%)	0 / 25 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 29 (0.00%)	2 / 34 (5.88%)	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 11 (9.09%)	1 / 12 (8.33%)	1 / 13 (7.69%)	1 / 14 (7.14%)	2 / 27 (7.41%)	1 / 26 (3.85%)	1 / 24 (4.17%)	9 / 93 (9.68%)
occurrences all number	3	10	0	2	0	0	1	0	2	0	0	1	2	1	1	2	3	3	11
furuncle
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	3 / 93 (3.23%)	1 / 184 (0.54%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	1 / 14 (7.14%)	1 / 27 (3.70%)	0 / 26 (0.00%)	2 / 24 (8.33%)	0 / 93 (0.00%)
occurrences all number	3	1	0	0	0	0	0	0	0	0	0	0	1	0	1	1	0	2	0
gastroenteritis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	4 / 184 (2.17%)	2 / 92 (2.17%)	0 / 24 (0.00%)	1 / 25 (4.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	2 / 7 (28.57%)	1 / 11 (9.09%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	1 / 26 (3.85%)	0 / 24 (0.00%)	2 / 93 (2.15%)
occurrences all number	0	5	2	0	1	0	0	0	0	0	2	1	0	0	0	0	1	0	2
genital candidiasis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
genital infection bacterial
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
herpes simplex
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 93 (1.08%)	5 / 184 (2.72%)	6 / 92 (6.52%)	2 / 24 (8.33%)	1 / 25 (4.00%)	0 / 16 (0.00%)	3 / 16 (18.75%)	2 / 29 (6.90%)	0 / 34 (0.00%)	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 11 (0.00%)	0 / 12 (0.00%)	2 / 13 (15.38%)	1 / 14 (7.14%)	1 / 27 (3.70%)	0 / 26 (0.00%)	2 / 24 (8.33%)	1 / 93 (1.08%)
occurrences all number	2	5	7	2	2	0	5	3	0	0	1	0	0	2	1	1	0	3	1
herpes zoster
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	6 / 184 (3.26%)	3 / 92 (3.26%)	1 / 24 (4.17%)	1 / 25 (4.00%)	0 / 16 (0.00%)	2 / 16 (12.50%)	0 / 29 (0.00%)	3 / 34 (8.82%)	3 / 22 (13.64%)	1 / 7 (14.29%)	0 / 11 (0.00%)	1 / 12 (8.33%)	2 / 13 (15.38%)	0 / 14 (0.00%)	1 / 27 (3.70%)	4 / 26 (15.38%)	1 / 24 (4.17%)	4 / 93 (4.30%)
occurrences all number	0	6	3	1	1	0	2	0	3	3	2	0	1	2	0	1	4	1	4
hordeolum
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	2 / 92 (2.17%)	2 / 24 (8.33%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 29 (3.45%)	0 / 34 (0.00%)	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	2 / 24 (8.33%)	0 / 93 (0.00%)
occurrences all number	0	0	2	2	0	0	0	1	0	0	1	0	1	0	0	0	0	2	0
impetigo
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 93 (1.08%)	5 / 184 (2.72%)	1 / 92 (1.09%)	0 / 24 (0.00%)	1 / 25 (4.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 29 (0.00%)	1 / 34 (2.94%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)	0 / 27 (0.00%)	1 / 26 (3.85%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	1	5	1	0	1	0	1	0	1	0	0	0	0	0	1	0	1	0	0
influenza
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	2 / 93 (2.15%)	15 / 184 (8.15%)	14 / 92 (15.22%)	1 / 24 (4.17%)	3 / 25 (12.00%)	1 / 16 (6.25%)	2 / 16 (12.50%)	1 / 29 (3.45%)	0 / 34 (0.00%)	1 / 22 (4.55%)	0 / 7 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	1 / 13 (7.69%)	0 / 14 (0.00%)	2 / 27 (7.41%)	2 / 26 (7.69%)	1 / 24 (4.17%)	3 / 93 (3.23%)
occurrences all number	2	18	15	1	3	1	2	1	0	1	0	0	1	1	0	2	2	1	4
labyrinthitis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	2 / 24 (8.33%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0
molluscum contagiosum
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	3 / 184 (1.63%)	0 / 92 (0.00%)	1 / 24 (4.17%)	0 / 25 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)	0 / 27 (0.00%)	1 / 26 (3.85%)	1 / 24 (4.17%)	0 / 93 (0.00%)
occurrences all number	0	3	0	1	0	0	1	0	0	0	0	0	0	1	0	0	1	1	0
nasopharyngitis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	14 / 93 (15.05%)	36 / 184 (19.57%)	34 / 92 (36.96%)	8 / 24 (33.33%)	3 / 25 (12.00%)	3 / 16 (18.75%)	3 / 16 (18.75%)	3 / 29 (10.34%)	4 / 34 (11.76%)	5 / 22 (22.73%)	4 / 7 (57.14%)	1 / 11 (9.09%)	6 / 12 (50.00%)	2 / 13 (15.38%)	1 / 14 (7.14%)	3 / 27 (11.11%)	3 / 26 (11.54%)	2 / 24 (8.33%)	16 / 93 (17.20%)
occurrences all number	25	48	45	11	4	3	7	3	5	5	5	2	7	2	1	3	3	3	20
ophthalmic herpes simplex
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	3 / 184 (1.63%)	0 / 92 (0.00%)	0 / 24 (0.00%)	1 / 25 (4.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	2 / 12 (16.67%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	1 / 24 (4.17%)	0 / 93 (0.00%)
occurrences all number	0	3	0	0	2	0	1	0	0	0	0	0	2	0	0	0	0	1	0
oral herpes
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	6 / 93 (6.45%)	6 / 184 (3.26%)	7 / 92 (7.61%)	1 / 24 (4.17%)	2 / 25 (8.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 29 (0.00%)	1 / 34 (2.94%)	3 / 22 (13.64%)	2 / 7 (28.57%)	1 / 11 (9.09%)	1 / 12 (8.33%)	2 / 13 (15.38%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	1 / 24 (4.17%)	5 / 93 (5.38%)
occurrences all number	6	9	13	1	4	0	1	0	1	3	2	3	3	3	0	0	0	2	7
otitis externa
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	3 / 184 (1.63%)	1 / 92 (1.09%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)	0 / 27 (0.00%)	1 / 26 (3.85%)	0 / 24 (0.00%)	1 / 93 (1.08%)
occurrences all number	0	3	1	0	0	0	0	0	0	0	1	0	0	1	0	0	2	0	1
paronychia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	2 / 92 (2.17%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	1 / 22 (4.55%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)	0 / 27 (0.00%)	1 / 26 (3.85%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	0	1	0	0	0	0	2	0	1	0	0
peritonsillar abscess
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
perichondritis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	1 / 184 (0.54%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	1 / 22 (4.55%)	0 / 7 (0.00%)	1 / 11 (9.09%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	2	0	1	0	0	0	0	0	0	0
pharyngitis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	4 / 93 (4.30%)	4 / 184 (2.17%)	1 / 92 (1.09%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	2 / 34 (5.88%)	0 / 22 (0.00%)	2 / 7 (28.57%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	1 / 93 (1.08%)
occurrences all number	4	4	1	0	0	0	0	0	2	0	2	0	0	0	0	0	0	0	1
pneumonia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	1 / 184 (0.54%)	0 / 92 (0.00%)	0 / 24 (0.00%)	1 / 25 (4.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 11 (9.09%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	2 / 93 (2.15%)
occurrences all number	0	1	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	0	2
post-acute covid-19 syndrome
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 29 (3.45%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0
pyoderma
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
pulpitis dental
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	2 / 184 (1.09%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	2 / 93 (2.15%)
occurrences all number	0	2	0	0	0	3	0	0	0	0	0	0	0	0	0	0	0	0	2
rhinitis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 93 (1.08%)	6 / 184 (3.26%)	3 / 92 (3.26%)	0 / 24 (0.00%)	1 / 25 (4.00%)	0 / 16 (0.00%)	2 / 16 (12.50%)	0 / 29 (0.00%)	2 / 34 (5.88%)	2 / 22 (9.09%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	1 / 93 (1.08%)
occurrences all number	1	6	3	0	1	0	2	0	3	2	0	0	0	0	0	0	0	0	1
skin infection
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 93 (1.08%)	4 / 184 (2.17%)	4 / 92 (4.35%)	1 / 24 (4.17%)	0 / 25 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	1 / 29 (3.45%)	0 / 34 (0.00%)	1 / 22 (4.55%)	0 / 7 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	1 / 14 (7.14%)	1 / 27 (3.70%)	4 / 26 (15.38%)	1 / 24 (4.17%)	3 / 93 (3.23%)
occurrences all number	1	4	5	2	0	0	1	1	0	1	0	0	1	0	1	1	6	1	4
suspected covid-19
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	1 / 24 (4.17%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
subcutaneous abscess
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
tinea pedis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 93 (1.08%)	0 / 184 (0.00%)	1 / 92 (1.09%)	0 / 24 (0.00%)	1 / 25 (4.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	2 / 93 (2.15%)
occurrences all number	1	0	1	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	2
tonsillitis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 93 (1.08%)	5 / 184 (2.72%)	1 / 92 (1.09%)	0 / 24 (0.00%)	0 / 25 (0.00%)	2 / 16 (12.50%)	0 / 16 (0.00%)	1 / 29 (3.45%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	1	5	1	0	0	2	0	1	0	0	0	0	0	0	0	0	0	0	0
tooth infection
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	2 / 184 (1.09%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 29 (3.45%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	2	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0
urinary tract infection
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	4 / 184 (2.17%)	5 / 92 (5.43%)	0 / 24 (0.00%)	1 / 25 (4.00%)	0 / 16 (0.00%)	2 / 16 (12.50%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	0 / 14 (0.00%)	1 / 27 (3.70%)	0 / 26 (0.00%)	0 / 24 (0.00%)	1 / 93 (1.08%)
occurrences all number	0	7	5	0	1	0	2	0	0	0	1	0	1	0	0	1	0	0	1
upper respiratory tract infection
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	7 / 184 (3.80%)	4 / 92 (4.35%)	0 / 24 (0.00%)	0 / 25 (0.00%)	3 / 16 (18.75%)	0 / 16 (0.00%)	1 / 29 (3.45%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)	1 / 27 (3.70%)	0 / 26 (0.00%)	3 / 24 (12.50%)	4 / 93 (4.30%)
occurrences all number	0	10	5	0	0	3	0	2	0	0	0	0	0	1	0	1	0	4	5
vaginal infection
alternative dictionary used: MedDRA 25.1
subjects affected / exposed ^[12]	1 / 44 (2.27%)	0 / 52 (0.00%)	0 / 35 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 35 (0.00%)
occurrences all number	1	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
viral infection
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
vulvovaginal candidiasis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed ^[13]	0 / 44 (0.00%)	2 / 52 (3.85%)	0 / 35 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 14 (0.00%)	1 / 13 (7.69%)	1 / 8 (12.50%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 35 (0.00%)
occurrences all number	0	2	0	0	1	0	0	0	1	1	1	0	0	0	0	1	0	0	0
Metabolism and nutrition disorders
decreased appetite
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	1 / 92 (1.09%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
folate deficiency
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
glucose tolerance impaired
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
hypercholesterolaemia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	3 / 184 (1.63%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 16 (6.25%)	1 / 16 (6.25%)	0 / 29 (0.00%)	1 / 34 (2.94%)	1 / 22 (4.55%)	0 / 7 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	1 / 26 (3.85%)	1 / 24 (4.17%)	1 / 93 (1.08%)
occurrences all number	0	3	0	0	0	1	1	0	1	1	0	0	1	0	0	0	1	1	1
hyperglycaemia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
hypertriglyceridaemia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	3 / 184 (1.63%)	0 / 92 (0.00%)	0 / 24 (0.00%)	1 / 25 (4.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	2 / 27 (7.41%)	1 / 26 (3.85%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	3	0	0	1	1	0	0	0	0	0	0	0	0	0	2	2	0	0
hyperlipidaemia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	1 / 24 (4.17%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	1 / 24 (4.17%)	0 / 93 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	0	1	0
iron deficiency
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
obesity
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
type 2 diabetes mellitus
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 29 (0.00%)	0 / 34 (0.00%)	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
vitamin d deficiency
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 93 (0.00%)	0 / 184 (0.00%)	0 / 92 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	2 / 29 (6.90%)	0 / 34 (0.00%)	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)	0 / 27 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 93 (0.00%)
occurrences all number	0	0	0	0	0	1	0	2	0	0	0	0	0	0	1	0	0	0	0

Notes
[2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Gender specific events occurring only in male or female participants have had the number of participants At Risk adjusted accordingly.
[3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Gender specific events occurring only in male or female participants have had the number of participants At Risk adjusted accordingly.
[4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Gender specific events occurring only in male or female participants have had the number of participants At Risk adjusted accordingly.
[5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Gender specific events occurring only in male or female participants have had the number of participants At Risk adjusted accordingly.
[6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Gender specific events occurring only in male or female participants have had the number of participants At Risk adjusted accordingly.
[7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Gender specific events occurring only in male or female participants have had the number of participants At Risk adjusted accordingly.
[8] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Gender specific events occurring only in male or female participants have had the number of participants At Risk adjusted accordingly.
[9] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Gender specific events occurring only in male or female participants have had the number of participants At Risk adjusted accordingly.
[10] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Gender specific events occurring only in male or female participants have had the number of participants At Risk adjusted accordingly.
[11] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Gender specific events occurring only in male or female participants have had the number of participants At Risk adjusted accordingly.
[12] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Gender specific events occurring only in male or female participants have had the number of participants At Risk adjusted accordingly.
[13] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Gender specific events occurring only in male or female participants have had the number of participants At Risk adjusted accordingly.

More information

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Were there any global substantial amendments to the protocol? Yes

09 May 2019

Amendment (c ): Key secondary endpoints were changed.

19 Sep 2019

Amendment (d): Update the Primary Endpoint from IGA 0,1 to EASI 75.

06 Dec 2019

Amendment (e): Updated risk information as well as the addition of a new bridging extension post week 104 (V22) of up to 96 additional weeks (for a total of 200 weeks).

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75) (Placebo, 2 mg or 4 mg Baricitinib)

Primary: Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75) (Placebo, 2 mg or 4 mg Baricitinib)

Secondary: Percentage of Participants Achieving EASI75 (Placebo, 1 mg Baricitinib)

Secondary: Percentage of Participants Achieving EASI75 (Placebo, 1 mg Baricitinib)

Secondary: Percentage of Participants Achieving IGA of 0 or 1 with a ≥ 2 Point Improvement

Secondary: Percentage of Participants Achieving IGA of 0 or 1 with a ≥ 2 Point Improvement

Secondary: Percentage of Participants Achieving EASI90

Secondary: Percentage of Participants Achieving EASI90

Secondary: Percent Change from Baseline in EASI Score

Secondary: Percent Change from Baseline in EASI Score

Secondary: Percentage of Participants Achieving SCORing Atopic Dermatitis 75 (SCORAD75)

Secondary: Percentage of Participants Achieving SCORing Atopic Dermatitis 75 (SCORAD75)

Secondary: Percentage of Participants Achieving a 4-Point Improvement in Itch Numeric Rating Scale (NRS)

Secondary: Percentage of Participants Achieving a 4-Point Improvement in Itch Numeric Rating Scale (NRS)

Secondary: Change from Baseline in the Score of Item 2 of the Atopic Dermatitis Sleep Scale (ADSS)

Secondary: Change from Baseline in the Score of Item 2 of the Atopic Dermatitis Sleep Scale (ADSS)

Secondary: Change from Baseline in Skin Pain NRS

Secondary: Change from Baseline in Skin Pain NRS

Secondary: Percentage of Participants Achieving IGA of 0 or 1 with a >=2-point improvement

Secondary: Percentage of Participants Achieving IGA of 0 or 1 with a >=2-point improvement

Secondary: Percentage of Participants Achieving EASI50

Secondary: Percentage of Participants Achieving EASI50

Secondary: Percentage of Participants Achieving EASI75

Secondary: Percentage of Participants Achieving EASI75

Secondary: Percentage of Participants Achieving IGA of 0

Secondary: Percentage of Participants Achieving IGA of 0

Secondary: Change from Baseline in SCORAD

Secondary: Change from Baseline in SCORAD

Secondary: Percentage of Participants Achieving SCORAD90

Secondary: Percentage of Participants Achieving SCORAD90

Secondary: Change from Baseline in Body Surface Area (BSA) Affected

Secondary: Change from Baseline in Body Surface Area (BSA) Affected

Secondary: Percentage of Participants Developing Skin Infections Requiring Antibiotic Treatment

Secondary: Percentage of Participants Developing Skin Infections Requiring Antibiotic Treatment

Secondary: Mean Number of Days without Topical Corticosteroids (TCS) Use

Secondary: Mean Number of Days without Topical Corticosteroids (TCS) Use

Secondary: Mean Gram Quantity of Low and Moderate Potency Background Topical Corticosteroid (TCS) Used (Tube Weights)

Secondary: Mean Gram Quantity of Low and Moderate Potency Background Topical Corticosteroid (TCS) Used (Tube Weights)

Secondary: Percent Change from Baseline in Itch NRS

Secondary: Percent Change from Baseline in Itch NRS

Secondary: Percent Change From Baseline in Itch NRS at Week 24

Secondary: Percent Change From Baseline in Itch NRS at Week 24

Secondary: Change from Baseline in the Total Score of the Patient Oriented Eczema Measure (POEM)

Secondary: Change from Baseline in the Total Score of the Patient Oriented Eczema Measure (POEM)

Secondary: Change from Baseline in the Patient Global Impression of Severity -Atopic Dermatitis (PGI-S-AD) Score

Secondary: Change from Baseline in the Patient Global Impression of Severity -Atopic Dermatitis (PGI-S-AD) Score

Secondary: Change from Baseline on the Hospital Anxiety Depression Scale (HADS)

Secondary: Change from Baseline on the Hospital Anxiety Depression Scale (HADS)

Secondary: Change from Baseline in the Dermatology Life Quality Index (DLQI)

Secondary: Change from Baseline in the Dermatology Life Quality Index (DLQI)

Secondary: Change from Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire

Secondary: Change from Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire

Secondary: Change from Baseline in the European Quality of Life–5 Dimensions–5 Levels (EQ-5D-5L) Index Score United States and United Kingdom Algorithm

Secondary: Change from Baseline in the European Quality of Life–5 Dimensions–5 Levels (EQ-5D-5L) Index Score United States and United Kingdom Algorithm

Secondary: Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Visual Analog Score (VAS)

Secondary: Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Visual Analog Score (VAS)

Secondary: Percentage of Participants Achieving EASI75

Secondary: Percentage of Participants Achieving EASI75

Secondary: Percent Change From Baseline in Itch NRS at Week 52

Secondary: Percent Change From Baseline in Itch NRS at Week 52

Secondary: Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed at 16 Weeks After Rerandomization (Week 68) Randomized Downtitration (All Participants Entering the Substudy)

Secondary: Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed at 16 Weeks After Rerandomization (Week 68) Randomized Downtitration (All Participants Entering the Substudy)

Secondary: Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed at 16 Weeks After Rerandomization (Week 104) Randomized Downtitration (All Participants Entering the Substudy)

Secondary: Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed at 16 Weeks After Rerandomization (Week 104) Randomized Downtitration (All Participants Entering the Substudy)

Secondary: Percentage of Participants With a Response of IGA 0, 1 Assessed at 16 Weeks After Rerandomization (Week 68) Randomized Downtitration (All Participants Entering tSubstudy)

Secondary: Percentage of Participants With a Response of IGA 0, 1 Assessed at 16 Weeks After Rerandomization (Week 68) Randomized Downtitration (All Participants Entering tSubstudy)

Secondary: Percentage of Participants With a Response of IGA 0, 1 Assessed at 16 Weeks After Rerandomization (Week 104) Randomized Downtitration (All Participants Entering the Substudy)

Secondary: Percentage of Participants With a Response of IGA 0, 1 Assessed at 16 Weeks After Rerandomization (Week 104) Randomized Downtitration (All Participants Entering the Substudy)

Secondary: Percentage of Participants With a Response of EASI75 From Baseline Assessed at 16 Weeks After Rerandomization (Week 68) Randomized Downtitration (All Participants Entering the Substudy)

Secondary: Percentage of Participants With a Response of EASI75 From Baseline Assessed at 16 Weeks After Rerandomization (Week 68) Randomized Downtitration (All Participants Entering the Substudy)

Secondary: Percentage of Participants With a Response of EASI75 From Baseline Assessed at 16 Weeks After Rerandomization (Week 104) Randomized Downtitration (All Participants Entering the Substudy)