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Clinical Trial Results:
A Phase 3 Multicenter, Double-Blind Study to Evaluate the Long-Term Safety and Efficacy of Baricitinib in Adult Patients with Atopic Dermatitis

Summary
EudraCT number	2017-000873-35
Trial protocol	DE CZ HU AT ES PL FR DK IT
Global end of trial date	12 Jul 2023

Results information
Results version number	v2(current)
This version publication date	27 Jul 2024
First version publication date	02 Jun 2022
Other versions	v1
Version creation reason	New data added to full data set LPV Results

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-JAHN

ISRCTN number

US NCT number

NCT03334435

WHO universal trial number (UTN)

Other trial identifiers

Trial Number: 16587

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

12 Jul 2023

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

12 Jul 2023

Was the trial ended prematurely?

Main objective of the trial

The purpose of this study is to evaluate the long-term safety and efficacy of baricitinib in participants with atopic dermatitis. Participants were enrolled in this study from the originating studies (JAHL, JAHM, JAIY) or were directly enrolled in the open-label arm.

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

Background topical corticosteroids were permitted for use at the discretion of the investigator.

Evidence for comparator

Actual start date of recruitment

28 Mar 2018

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 114

Country: Number of subjects enrolled

Hungary: 72

Country: Number of subjects enrolled

Czechia: 102

Country: Number of subjects enrolled

Japan: 244

Country: Number of subjects enrolled

Switzerland: 18

Country: Number of subjects enrolled

India: 31

Country: Number of subjects enrolled

Spain: 80

Country: Number of subjects enrolled

Russian Federation: 51

Country: Number of subjects enrolled

Austria: 49

Country: Number of subjects enrolled

Korea, Republic of: 107

Country: Number of subjects enrolled

Taiwan: 90

Country: Number of subjects enrolled

Denmark: 7

Country: Number of subjects enrolled

Poland: 132

Country: Number of subjects enrolled

Italy: 68

Country: Number of subjects enrolled

Mexico: 107

Country: Number of subjects enrolled

Israel: 34

Country: Number of subjects enrolled

France: 34

Country: Number of subjects enrolled

Australia: 109

Country: Number of subjects enrolled

Germany: 196

Worldwide total number of subjects

1645

EEA total number of subjects

740

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)

1602

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Participants who entered Study JAHN were classified as “Responders and Partial Responders (RPR): Investigator's Global Assessment (IGA) of (0,1, or 2) at entry to study JAHN and never rescued in originating study” or “Non-responders (NR): those not meeting definition of RPR".

Screening details

The study has two treatment periods: Treatment period 1, from Week 0 up to Week 52, and Treatment period 2, from Week 52 through Week 200 (which included randomized withdrawal and downtitration substudy).

Period 1 title

Treatment Period 1: Week 0 to Week 52

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants from previous Baricitinib monotherapy studies (JAHL, JAHM) and combination therapy study (JAIY) were randomized or assigned to this arm to receive placebo orally.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally.

Bari (Baricitinib) 1- milligram (mg)

Arm description

Participants from previous Baricitinib monotherapy studies (JAHL, JAHM) were randomized or assigned to this arm to receive Baricitinib 1 mg orally.

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

Administered Baricitinib 1 mg orally.

Bari 2-mg

Arm description

Participants from previous Baricitinib monotherapy studies (JAHL, JAHM) and combination study (JAIY) were randomized or assigned to this arm to receive Baricitinib 2 mg orally.

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

Administered Baricitinib 2 mg orally.

Bari 4-mg

Arm description

Participants from previous Baricitinib monotherapy studies (JAHL, JAHM) and combination study (JAIY) were randomized or assigned to this arm to receive Baricitinib 4 mg orally.

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

Administered Baricitinib 4 mg orally.

Bari 2-mg Open-Label Addendum

Arm description

Participants were directly enrolled to this open-label arm to receive Baricitinib 2-mg orally.

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

Administered orally

Number of subjects in period 1	Placebo	Bari (Baricitinib) 1- milligram (mg)	Bari 2-mg	Bari 4-mg	Bari 2-mg Open-Label Addendum
Started	91	45	519	743	247
Completed	2	2	12	15	5
Not completed	89	43	507	728	242
Adverse event, serious fatal	-	-	-	1	-
Consent withdrawn by subject	11	4	38	42	20
Adverse event, non-fatal	2	1	9	23	13
Not specified	-	1	3	2	1
Ongoing as of Week 52	70	32	379	519	146
Lost to follow-up	3	-	2	1	1
Lack of efficacy	3	5	76	140	61

Period 2 title

Treatment Period 2: 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

2 mg Bari to Placebo Substudy

Arm description

Participants who received Baricitinib 2 mg at the start of Study JAHN were rerandomized at week 52 or assigned to this arm to receive placebo orally.

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

Administered placebo orally.

2 mg Bari to 1 mg Bari Substudy

Arm description

Participants who received Baricitinib 2 mg at the start of Study JAHN were rerandomized at week 52 or assigned to this arm to receive Baricitinib 1 mg orally.

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

Administered Baricitinib 1 mg orally.

2 mg Bari to 2 mg Bari Substudy

Arm description

Participants who received Baricitinib 2 mg at the start of Study JAHN were rerandomized at week 52 or assigned to this arm to receive Baricitinib 2 mg orally.

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

Administered Baricitinib 2 mg orally.

4 mg Bari to Placebo Substudy

Arm description

Participants who received Baricitinib 4 mg at the start of Study JAHN were rerandomized at week 52 or assigned to this arm to receive placebo orally.

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

Administered orally.

4 mg Bari to 2 mg Bari Substudy

Arm description

Participants who received Baricitinib 4 mg at the start of Study JAHN were rerandomized at week 52 or assigned to this arm to receive Baricitinib 2 mg orally.

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

Administered Baricitinib 2 mg orally.

4 mg Bari to 4 mg Bari Substudy

Arm description

Participants who received Baricitinib 4 mg at the start of Study JAHN were rerandomized at week 52 or assigned to this arm to receive Baricitinib 4 mg orally.

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

Administered Baricitinib 4 mg orally.

Placebo to Placebo Non-substudy

Arm description

Participants who received placebo at the start of Study JAHN who were not eligible to enter the substudy at week 52 assigned to this arm to receive placebo orally.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally.

1 mg Bari to 1 mg Bari Non-substudy

Arm description

Participants who received Baricitinib 1 mg at the start of Study JAHN who were not eligible to enter the substudy at week 52 assigned to this arm to receive Baricitinib 1 mg orally.

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

Administered Baricitinib 1 mg orally.

2 mg Bari to 2 mg Bari Non-substudy

Arm description

Participants who received Baricitinib 2 mg at the start of Study JAHN who were not eligible to enter the substudy at week 52 assigned to this arm to receive Baricitinib 2 mg orally.

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

Administered Baricitinib 2 mg orally.

4 mg Bari to 4 mg Bari Non-substudy

Arm description

Participants who received Baricitinib 4 mg at the start of Study JAHN who were not eligible to enter the substudy at week 52 assigned to this arm to receive Baricitinib 4 mg orally.

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

Administered Baricitinib 4 mg orally.

Number of subjects in period 2	2 mg Bari to Placebo Substudy	2 mg Bari to 1 mg Bari Substudy	2 mg Bari to 2 mg Bari Substudy	4 mg Bari to Placebo Substudy	4 mg Bari to 2 mg Bari Substudy	4 mg Bari to 4 mg Bari Substudy	Placebo to Placebo Non-substudy	1 mg Bari to 1 mg Bari Non-substudy	2 mg Bari to 2 mg Bari Non-substudy	4 mg Bari to 4 mg Bari Non-substudy
Started	92	91	92	84	84	84	70	32	249	264
Completed	29	40	38	34	40	35	28	23	60	68
Not completed	63	51	54	50	44	49	42	9	189	196
Adverse event, serious fatal	1	-	-	-	-	-	-	-	-	1
Physician Decision	1	-	-	-	-	1	-	-	-	1
Withdrawal due to Caregiver Circumstances	-	-	-	-	-	-	1	-	1	-
Study Terminated by Sponsor	17	21	17	19	15	17	16	3	66	70
Sponsor decision	-	-	1	1	-	1	3	1	-	-
Consent withdrawn by subject	23	15	20	17	10	11	8	-	41	32
Adverse event, non-fatal	6	1	2	2	3	9	3	2	11	13
Protocol deviation	1	1	-	-	-	-	1	1	2	-
Pregnancy	-	-	-	-	-	-	1	-	1	1
Lost to follow-up	-	2	2	3	1	1	1	-	4	4
Physician is retiring	1	1	1	1	3	1	1	-	-	-
Lack of efficacy	13	10	11	7	12	8	7	2	63	72
Protocol deviation	-	-	-	-	-	-	-	-	-	2

Baseline characteristics

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Reporting group title

Placebo

Reporting group description

Participants from previous Baricitinib monotherapy studies (JAHL, JAHM) and combination therapy study (JAIY) were randomized or assigned to this arm to receive placebo orally.

Reporting group title

Bari (Baricitinib) 1- milligram (mg)

Reporting group description

Participants from previous Baricitinib monotherapy studies (JAHL, JAHM) were randomized or assigned to this arm to receive Baricitinib 1 mg orally.

Reporting group title

Bari 2-mg

Reporting group description

Participants from previous Baricitinib monotherapy studies (JAHL, JAHM) and combination study (JAIY) were randomized or assigned to this arm to receive Baricitinib 2 mg orally.

Reporting group title

Bari 4-mg

Reporting group description

Participants from previous Baricitinib monotherapy studies (JAHL, JAHM) and combination study (JAIY) were randomized or assigned to this arm to receive Baricitinib 4 mg orally.

Reporting group title

Bari 2-mg Open-Label Addendum

Reporting group description

Participants were directly enrolled to this open-label arm to receive Baricitinib 2-mg orally.

Reporting group values	Placebo	Bari (Baricitinib) 1- milligram (mg)	Bari 2-mg	Bari 4-mg	Bari 2-mg Open-Label Addendum	Total
Number of subjects	91	45	519	743	247	1645
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	35.2 ( 14.06 )	33.5 ( 8.49 )	34.2 ( 12.69 )	35.6 ( 12.85 )	34.9 ( 12.98 )	-
Gender categorical
Units: Subjects
Female	44	16	206	239	112	617
Male	47	29	313	504	135	1028
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	6	4	10	6	16	42
Asian	32	7	174	282	13	508
Native Hawaiian or Other Pacific Islander	0	0	1	0	0	1
Black or African American	0	0	1	1	1	3
White	48	32	315	429	211	1035
More than one race	5	2	18	23	6	54
Unknown or Not Reported	0	0	0	2	0	2
Region of Enrollment
Units: Subjects
Argentina	6	2	36	46	24	114
Hungary	7	2	15	21	27	72
Czechia	3	3	22	46	28	102
Japan	11	3	89	141	0	244
Switzerland	0	1	5	9	3	18
India	5	0	7	19	0	31
Spain	2	1	27	26	24	80
Russia	0	1	9	13	28	51
Austria	2	0	12	23	12	49
South Korea	9	1	39	58	0	107
Taiwan	8	2	30	50	0	90
Denmark	0	0	0	0	7	7
Poland	10	7	45	70	0	132
Italy	7	4	16	26	15	68
Mexico	9	5	29	21	43	107
Israel	1	0	16	13	4	34
France	0	0	15	19	0	34
Australia	4	1	30	42	32	109
Germany	7	12	77	100	0	196
Ethnicity (NIH/OMB
Units: Subjects
HISPANIC OR LATINO	15	10	70	87	72	254
NOT HISPANIC OR LATINO	57	32	332	467	165	1053
UNKNOWN OR NOT REPORTED	19	3	117	189	10	338

End points

Top of page

Reporting group title

Placebo

Reporting group description

Participants from previous Baricitinib monotherapy studies (JAHL, JAHM) and combination therapy study (JAIY) were randomized or assigned to this arm to receive placebo orally.

Reporting group title

Bari (Baricitinib) 1- milligram (mg)

Reporting group description

Participants from previous Baricitinib monotherapy studies (JAHL, JAHM) were randomized or assigned to this arm to receive Baricitinib 1 mg orally.

Reporting group title

Bari 2-mg

Reporting group description

Participants from previous Baricitinib monotherapy studies (JAHL, JAHM) and combination study (JAIY) were randomized or assigned to this arm to receive Baricitinib 2 mg orally.

Reporting group title

Bari 4-mg

Reporting group description

Participants from previous Baricitinib monotherapy studies (JAHL, JAHM) and combination study (JAIY) were randomized or assigned to this arm to receive Baricitinib 4 mg orally.

Reporting group title

Bari 2-mg Open-Label Addendum

Reporting group description

Participants were directly enrolled to this open-label arm to receive Baricitinib 2-mg orally.

Reporting group title

2 mg Bari to Placebo Substudy

Reporting group description

Participants who received Baricitinib 2 mg at the start of Study JAHN were rerandomized at week 52 or assigned to this arm to receive placebo orally.

Reporting group title

2 mg Bari to 1 mg Bari Substudy

Reporting group description

Participants who received Baricitinib 2 mg at the start of Study JAHN were rerandomized at week 52 or assigned to this arm to receive Baricitinib 1 mg orally.

Reporting group title

2 mg Bari to 2 mg Bari Substudy

Reporting group description

Participants who received Baricitinib 2 mg at the start of Study JAHN were rerandomized at week 52 or assigned to this arm to receive Baricitinib 2 mg orally.

Reporting group title

4 mg Bari to Placebo Substudy

Reporting group description

Participants who received Baricitinib 4 mg at the start of Study JAHN were rerandomized at week 52 or assigned to this arm to receive placebo orally.

Reporting group title

4 mg Bari to 2 mg Bari Substudy

Reporting group description

Participants who received Baricitinib 4 mg at the start of Study JAHN were rerandomized at week 52 or assigned to this arm to receive Baricitinib 2 mg orally.

Reporting group title

4 mg Bari to 4 mg Bari Substudy

Reporting group description

Participants who received Baricitinib 4 mg at the start of Study JAHN were rerandomized at week 52 or assigned to this arm to receive Baricitinib 4 mg orally.

Reporting group title

Placebo to Placebo Non-substudy

Reporting group description

Participants who received placebo at the start of Study JAHN who were not eligible to enter the substudy at week 52 assigned to this arm to receive placebo orally.

Reporting group title

1 mg Bari to 1 mg Bari Non-substudy

Reporting group description

Participants who received Baricitinib 1 mg at the start of Study JAHN who were not eligible to enter the substudy at week 52 assigned to this arm to receive Baricitinib 1 mg orally.

Reporting group title

2 mg Bari to 2 mg Bari Non-substudy

Reporting group description

Participants who received Baricitinib 2 mg at the start of Study JAHN who were not eligible to enter the substudy at week 52 assigned to this arm to receive Baricitinib 2 mg orally.

Reporting group title

4 mg Bari to 4 mg Bari Non-substudy

Reporting group description

Participants who received Baricitinib 4 mg at the start of Study JAHN who were not eligible to enter the substudy at week 52 assigned to this arm to receive Baricitinib 4 mg orally.

Subject analysis set title

RPR-Placebo

Subject analysis set type

Per protocol

Subject analysis set description

RPR participants from previous Baricitinib monotherapy studies-JAHL and JAHM were assigned to remain in this arm to receive placebo orally.

Subject analysis set title

RPR-Bari 1-mg

Subject analysis set type

Per protocol

Subject analysis set description

RPR participants from previous Baricitinib monotherapy studies-JAHL and JAHM were assigned to remain in this arm to receive Baricitinib 1 mg orally.

Subject analysis set title

RPR-Bari 2-mg

Subject analysis set type

Per protocol

Subject analysis set description

RPR participants from previous Baricitinib monotherapy studies-JAHL and JAHM were assigned to remain in this arm to receive Baricitinib 2 mg orally.

Subject analysis set title

RPR-Bari 4-mg

Subject analysis set type

Per protocol

Subject analysis set description

RPR participants from previous Baricitinib monotherapy studies-JAHL and JAHM were assigned to remain in this arm to receive Baricitinib 4 mg orally.

Subject analysis set title

NR: Bari 1 mg to 2 mg

Subject analysis set type

Per protocol

Subject analysis set description

NR participants from previous Baricitinib monotherapy studies-JAHL and JAHM who received Baricitinib 1 mg and were re-randomized to this arm to receive Baricitinib 2 mg orally.

Subject analysis set title

NR: Bari 1 mg to 4 mg

Subject analysis set type

Per protocol

Subject analysis set description

NR participants from previous Baricitinib monotherapy studies-JAHL and JAHM who received Baricitinib 1 mg and were re-randomized to this arm to receive Baricitinib 4 mg orally.

Subject analysis set title

NR: Bari 2 mg to 2 mg

Subject analysis set type

Per protocol

Subject analysis set description

NR participants from previous Baricitinib monotherapy studies-JAHL and JAHM who received Baricitinib 2 mg and were re-randomized to this arm to receive Baricitinib 2 mg orally.

Subject analysis set title

NR: Bari 2 mg to 4 mg

Subject analysis set type

Per protocol

Subject analysis set description

NR participants from previous Baricitinib monotherapy studies-JAHL and JAHM who received Baricitinib 2 mg and were re-randomized to this arm to receive Baricitinib 4 mg orally.

Subject analysis set title

NR: Bari 4 mg to 4 mg

Subject analysis set type

Per protocol

Subject analysis set description

NR participants from previous Baricitinib monotherapy studies-JAHL and JAHM who received Baricitinib 4 mg and were re-randomized to this arm to receive Baricitinib 4 mg orally.

Subject analysis set title

NR: Placebo to Bari 2 mg

Subject analysis set type

Per protocol

Subject analysis set description

NR participants from previous Baricitinib monotherapy studies-JAHL and JAHM who received placebo and were re-randomized to this arm to receive Baricitinib 2 mg orally.

Subject analysis set title

NR: Placebo to Bari 4 mg

Subject analysis set type

Per protocol

Subject analysis set description

NR participants from previous Baricitinib monotherapy studies-JAHL and JAHM who received placebo and were re-randomized to this arm to receive Baricitinib 4 mg orally.

Primary: Responder and Partial Responders (RPR): Percentage of Participants from Monotherapy Studies (JAHL, JAHM) who Achieved a Response of Investigator's Global Assessment (IGA) 0 or 1

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End point title

Responder and Partial Responders (RPR): Percentage of Participants from Monotherapy Studies (JAHL, JAHM) who Achieved a Response of Investigator's Global Assessment (IGA) 0 or 1 ^[1]

End point description

The IGA measures the investigator's global assessment of the participant's overall severity of their atopic dermatitis (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. The results were analyzed using non-responder imputation (NRI). All participants who either discontinued the study treatment or discontinued the study for any reason at any time were defined as non-responders for the NRI analysis for categorical variables such as IGA 0/1. Analysis population description (APD): Modified Intent-to-treat Population: All RPR participants who received at least one dose of IP in JAHN. The participants here are from the previous Baricitinib monotherapy studies (JAHL and JAHM) as the results are presented as subsets of overall RPR population.

End point type

Primary

End point timeframe

Weeks 16, 36 and 52

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive statistics along with a confidence interval are performed for this end point.

End point values	RPR-Placebo	RPR-Bari 1-mg	RPR-Bari 2-mg	RPR-Bari 4-mg
Number of subjects analysed	52	45	54	70
Units: Percentage of participants
number (confidence interval 95%)
Week 16	36.5 (24.8 to 50.1)	46.7 (32.9 to 60.9)	59.3 (46.0 to 71.3)	48.6 (37.2 to 60.0)
Week 36	23.1 (13.7 to 36.1)	31.1 (19.5 to 45.7)	63.0 (49.6 to 74.6)	37.1 (26.8 to 48.9)
Week 52	28.8 (18.3 to 42.3)	35.6 (23.2 to 50.2)	50.0 (37.1 to 62.9)	40.0 (29.3 to 51.7)

No statistical analyses for this end point

Primary: RPR: Percentage of Participants from combination therapy study (JAIY) who achieved a response of IGA 0 or 1

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End point title

RPR: Percentage of Participants from combination therapy study (JAIY) who achieved a response of IGA 0 or 1 ^[2]

End point description

The IGA measures the investigator's global assessment of the participant's overall severity of their atopic dermatitis (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. The results were analyzed using NRI. All participants who either discontinued the study treatment or discontinued the study for any reason at any time were defined as non-responders for the NRI analysis for categorical variables such as IGA 0/1. APD: Modified Intent-to-treat Population: All RPR participants who received at least one dose of IP in JAHN. The participants here are from the previous Baricitinib combination therapy study (JAIY) as the results are presented as subsets of overall RPR population.

End point type

Primary

End point timeframe

Weeks 16, 36, and 52

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive statistics along with a confidence interval are performed for this end point.

End point values	RPR-Placebo	RPR-Bari 2-mg	RPR-Bari 4-mg
Number of subjects analysed	34	53	63
Units: Percentage of participants
number (confidence interval 95%)
Week 16	47.1 (31.5 to 63.3)	45.3 (32.7 to 58.5)	31.7 (21.6 to 44.0)
Week 36	41.2 (26.4 to 57.8)	24.5 (14.9 to 37.6)	30.2 (20.2 to 42.4)
Week 52	29.4 (16.8 to 46.2)	30.2 (19.5 to 43.5)	31.7 (21.6 to 44.0)

No statistical analyses for this end point

Secondary: RPR: Percentage of Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved a Response of IGA 0, 1 or 2

Top of page

End point title

RPR: Percentage of Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved a Response of IGA 0, 1 or 2

End point description

The IGA measures the investigator's global assessment of the participant's overall severity of their atopic dermatitis (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. The results were analyzed using NRI. All participants who either discontinued the study treatment or discontinued the study for any reason at any time were defined as non-responders for the NRI analysis for categorical variables such as IGA 0/1/2. APD: Modified Intent-to-treat Population: All RPR participants who received at least one dose of IP in JAHN. The participants here are from the previous Baricitinib monotherapy studies (JAHL and JAHM) as the results are presented as subsets of overall RPR population.

End point type

Secondary

End point timeframe

Weeks 16, 36, and 52

End point values	RPR-Placebo	RPR-Bari 1-mg	RPR-Bari 2-mg	RPR-Bari 4-mg
Number of subjects analysed	52	45	54	70
Units: Percentage of participants
number (confidence interval 95%)
Week 16	69.2 (55.7 to 80.1)	77.8 (63.7 to 87.5)	81.5 (69.2 to 89.6)	72.9 (61.5 to 81.9)
Week 36	48.1 (35.1 to 61.3)	60.0 (45.5 to 73.0)	81.5 (69.2 to 89.6)	58.6 (46.9 to 69.4)
Week 52	46.2 (33.3 to 59.5)	53.3 (39.1 to 67.1)	58.6 (46.9 to 69.4)	58.6 (46.9 to 69.4)

No statistical analyses for this end point

Secondary: RPR: Percentage of Participants From Combination Therapy study (JAIY) Who Achieved a Response of IGA 0, 1, or 2

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End point title

RPR: Percentage of Participants From Combination Therapy study (JAIY) Who Achieved a Response of IGA 0, 1, or 2

End point description

The IGA measures the investigator's global assessment of the participant's overall severity of their atopic dermatitis (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. The results were analyzed using NRI. All participants who either discontinued the study treatment or discontinued the study for any reason at any time were defined as non-responders for the NRI analysis for categorical variables such as IGA 0/1/2. APD: Modified Intent-to-treat Population: All RPR participants who received at least one dose of IP in JAHN. The participants here are from the previous Baricitinib combination therapy study (JAIY) as the results are presented as subsets of overall RPR population.

End point type

Secondary

End point timeframe

Weeks 16, 36, and 52

End point values	RPR-Placebo	RPR-Bari 2-mg	RPR-Bari 4-mg
Number of subjects analysed	34	53	63
Units: Percentage of participants
number (confidence interval 95%)
Week 16	70.6 (53.8 to 83.2)	73.6 (60.4 to 83.6)	63.5 (51.1 to 74.3)
Week 36	55.9 (39.5 to 71.1)	49.1 (36.1 to 62.1)	52.4 (40.3 to 64.2)
Week 52	50.0 (34.1 to 65.9)	54.7 (41.5 to 67.3)	52.4 (40.3 to 64.2)

No statistical analyses for this end point

Secondary: Non Responders (NR): Percentage of Baricitinib NR Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved a Response of IGA 0, 1 or 2

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End point title

Non Responders (NR): Percentage of Baricitinib NR Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved a Response of IGA 0, 1 or 2

End point description

The IGA measures the investigator's global assessment of the participant's overall severity of their atopic dermatitis (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. The results were analyzed using NRI. All participants who either discontinued the study treatment or discontinued the study for any reason at any time were defined as non-responders for the NRI analysis for categorical variables such as IGA 0/1/2. APD:Modified Intent-to-treat Population: All NR participants who received at least one dose of IP in JAHN. The participants here are from previous the Baricitinib monotherapy studies (JAHL and JAHM) as the results are presented as subsets of overall NR population.

End point type

Secondary

End point timeframe

Weeks 16, 36 and 52

End point values	NR: Bari 1 mg to 2 mg	NR: Bari 1 mg to 4 mg	NR: Bari 2 mg to 2 mg	NR: Bari 2 mg to 4 mg	NR: Bari 4 mg to 4 mg
Number of subjects analysed	87	81	84	78	156
Units: Percentage of participants
number (confidence interval 95%)
Week 16	46.0 (35.9 to 56.4)	55.6 (44.7 to 65.9)	47.6 (37.3 to 58.2)	43.6 (33.1 to 54.6)	40.4 (33.0 to 48.2)
Week 36	40.2 (30.6 to 50.7)	43.2 (33.0 to 54.1)	44.0 (33.9 to 54.7)	48.7 (37.9 to 59.6)	39.1 (31.8 to 46.9)
Week 52	31.0 (22.3 to 41.4)	48.1 (37.6 to 58.9)	44.0 (33.9 to 54.7)	38.5 (28.4 to 49.6)	41.0 (33.6 to 48.9)

No statistical analyses for this end point

Secondary: NR: Percentage of Baricitinib NR Participants From Combination Therapy Study (JAIY) Who Achieved a Response of IGA 0, 1 or 2

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End point title

NR: Percentage of Baricitinib NR Participants From Combination Therapy Study (JAIY) Who Achieved a Response of IGA 0, 1 or 2

End point description

The IGA measures the investigator's global assessment of the participant's overall severity of their atopic dermatitis (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. The results were analyzed using NRI. All participants who either discontinued the study treatment or discontinued the study for any reason at any time were defined as non-responders for the NRI analysis for categorical variables such as IGA 0/1/2. APD:Modified Intent-to-treat Population: All NR participants who received at least one dose of IP in JAHN. The participants here are from previous the previous Baricitinib combination therapy study (JAIY) as the results are presented as subsets of overall NR population.

End point type

Secondary

End point timeframe

Weeks 16, 36, and 52

End point values	NR: Bari 2 mg to 2 mg	NR: Bari 2 mg to 4 mg	NR: Bari 4 mg to 4 mg
Number of subjects analysed	20	21	39
Units: Percentage of participants
number (confidence interval 95%)
Week 16	35.0 (18.1 to 56.7)	57.1 (36.5 to 75.5)	30.8 (18.6 to 46.4)
Week 36	40.0 (21.9 to 61.3)	42.9 (24.5 to 63.5)	20.5 (10.8 to 35.5)
Week 52	45.0 (25.8 to 65.8)	42.9 (24.5 to 63.5)	28.2 (16.5 to 43.8)

No statistical analyses for this end point

Secondary: NR: Percentage of Baricitinib NR Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved a Response of IGA 0 or 1

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End point title

NR: Percentage of Baricitinib NR Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved a Response of IGA 0 or 1

End point description

The IGA measures the investigator's global assessment of the participant's overall severity of their atopic dermatitis (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. The results were analyzed using NRI. All participants who either discontinued the study treatment or discontinued the study for any reason at any time were defined as non-responders for the NRI analysis for categorical variables such as IGA 0/1. APD: Modified Intent-to-treat Population: All NR participants who received at least one dose of IP in JAHN. The participants here are from previous the Baricitinib monotherapy studies (JAHL and JAHM) as the results are presented as subsets of overall NR population.

End point type

Secondary

End point timeframe

Weeks 16, 36, 52

End point values	NR: Bari 1 mg to 2 mg	NR: Bari 1 mg to 4 mg	NR: Bari 2 mg to 2 mg	NR: Bari 2 mg to 4 mg	NR: Bari 4 mg to 4 mg
Number of subjects analysed	87	81	84	78	156
Units: Percentage of participants
number (confidence interval 95%)
Week 16	13.8 (8.1 to 22.6)	23.5 (15.6 to 33.8)	15.5 (9.3 to 24.7)	17.9 (11.0 to 27.9)	10.3 (6.4 to 16.0)
Week 36	13.8 (8.1 to 22.6)	12.3 (6.8 to 21.3)	10.7 (5.7 to 19.1)	16.7 (10.0 to 26.5)	16.7 (11.6 to 23.3)
Week 52	12.6 (7.2 to 21.2)	12.3 (6.8 to 21.3)	19.0 (12.1 to 28.7)	15.4 (9.0 to 25.0)	20.5 (14.9 to 27.5)

No statistical analyses for this end point

Secondary: NR: Percentage of Baricitinib NR Participants From Combination Therapy Study (JAIY) Who Achieved a Response of IGA 0 or 1

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End point title

NR: Percentage of Baricitinib NR Participants From Combination Therapy Study (JAIY) Who Achieved a Response of IGA 0 or 1

End point description

The IGA measures the investigator's global assessment of the participant's overall severity of their atopic dermatitis (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. The results were analyzed using NRI. All participants who either discontinued the study treatment or discontinued the study for any reason at any time were defined as non-responders for the NRI analysis for categorical variables such as IGA 0/1. APD: Modified Intent-to-treat Population: All NR participants who received at least one dose of IP in JAHN. The participants here are from previous the previous Baricitinib combination therapy study (JAIY) as the results are presented as subsets of overall NR population.

End point type

Secondary

End point timeframe

Weeks 16, 36, and 52

End point values	NR: Bari 2 mg to 2 mg	NR: Bari 2 mg to 4 mg	NR: Bari 4 mg to 4 mg
Number of subjects analysed	20	21	39
Units: Percentage of participants
number (confidence interval 95%)
Week 16	10.0 (2.8 to 30.1)	28.6 (13.8 to 50.0)	5.1 (1.4 to 16.9)
Week 36	15.0 (5.2 to 36.0)	23.8 (10.6 to 45.1)	15.4 (7.2 to 29.7)
Week 52	15.0 (5.2 to 36.0)	19.0 (7.7 to 40.0)	5.1 (1.4 to 16.9)

No statistical analyses for this end point

Secondary: RPR: Percentage of Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved a Response of Eczema Area and Severity Index (EASI)75

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End point title

RPR: Percentage of Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved a Response of Eczema Area and Severity Index (EASI)75

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 to 72 (severe). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score. APD: Modified Intent-to-treat Population: All RPR participants who received at least one dose of IP in JAHN. The participants here are from the previous Baricitinib monotherapy studies (JAHL and JAHM) as the results are presented as subsets of overall RPR population.

End point type

Secondary

End point timeframe

Weeks 16, 36, and 52 Weeks Results were analyzed using NRI. Participants who either discontinued study treatment or discontinued study for any reason at any time were defined as non-responders for the NRI analysis for categorical variable such as EASI 75

End point values	RPR-Placebo	RPR-Bari 1-mg	RPR-Bari 2-mg	RPR-Bari 4-mg
Number of subjects analysed	52	45	54	70
Units: Percentage of participants
number (confidence interval 95%)
Week 16	42.3 (29.9 to 55.8)	62.2 (47.6 to 74.9)	70.4 (57.2 to 80.9)	64.3 (52.6 to 74.5)
Week 36	44.2 (31.6 to 57.7)	46.7 (32.9 to 60.9)	74.1 (61.1 to 83.9)	51.4 (40.0 to 62.8)
Week 52	38.5 (26.5 to 52.0)	51.1 (37.0 to 65.0)	64.8 (51.5 to 76.2)	51.4 (40.0 to 62.8)

No statistical analyses for this end point

Secondary: RPR: Percentage of Participants From Combination Therapy Study (JAIY) Who Achieved a Response of EASI 75

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End point title

RPR: Percentage of Participants From Combination Therapy Study (JAIY) Who Achieved a Response of EASI 75

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 to 72 (severe). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score. APD: Modified Intent-to-treat Population: All RPR participants who received at least one dose of IP in JAHN. The participants here are from the previous Baricitinib combination therapy study (JAIY) as the results are presented as subsets of overall RPR population.

End point type

Secondary

End point timeframe

Weeks 16, 36, and 52 Results were analyzed using NRI. Participants who either discontinued study treatment or discontinued the study for any reason at any time were defined as non-responders for the NRI analysis for categorical variables such as EASI75

End point values	RPR-Placebo	RPR-Bari 2-mg	RPR-Bari 4-mg
Number of subjects analysed	34	53	63
Units: Percentage of participants
number (confidence interval 95%)
Week 16	55.9 (39.5 to 71.1)	67.9 (54.5 to 78.9)	55.6 (43.3 to 67.2)
Week 36	47.1 (31.5 to 63.3)	47.2 (34.4 to 60.3)	44.4 (32.8 to 56.7)
Week 52	38.2 (23.9 to 55.0)	52.8 (39.7 to 65.6)	42.9 (31.4 to 55.1)

No statistical analyses for this end point

Secondary: NR: Percentage of Baricitinib NR Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved a Response of EASI 75

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End point title

NR: Percentage of Baricitinib NR Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved a Response of EASI 75

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 to 72 (severe). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score. APD:Modified Intent-to-treat Population: All NR participants who received at least one dose of IP in JAHN. The participants here are from previous the Baricitinib monotherapy studies (JAHL and JAHM) as the results are presented as subsets of overall NR population.

End point type

Secondary

End point timeframe

End point values	NR: Bari 1 mg to 2 mg	NR: Bari 1 mg to 4 mg	NR: Bari 2 mg to 2 mg	NR: Bari 2 mg to 4 mg	NR: Bari 4 mg to 4 mg
Number of subjects analysed	87	81	84	78	156
Units: Percentage of participants
number (confidence interval 95%)
Week 16	33.3 (24.3 to 43.8)	43.2 (33.0 to 54.1)	38.1 (28.4 to 48.8)	38.5 (28.4 to 49.6)	26.9 (20.6 to 34.4)
Week 36	32.2 (23.3 to 42.6)	30.9 (21.9 to 41.6)	31.0 (22.1 to 41.5)	44.9 (34.3 to 55.9)	30.8 (24.1 to 38.4)
Week 52	28.7 (20.3 to 29.0)	35.8 (26.2 to 46.7)	34.5 (25.2 to 45.2)	34.6 (25.0 to 45.7)	33.3 (26.4 to 41.1)

No statistical analyses for this end point

Secondary: NR: Percentage of Baricitinib NR Participants From Combination Therapy Study (JAIY) Who Achieved a Response of EASI 75

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End point title

NR: Percentage of Baricitinib NR Participants From Combination Therapy Study (JAIY) Who Achieved a Response of EASI 75

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 to 72 (severe). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score. APD: Modified Intent-to-treat Population: All NR participants who received at least one dose of IP in JAHN. The participants here are from previous the previous Baricitinib combination therapy study (JAIY) as the results are presented as subsets of overall NR population.

End point type

Secondary

End point timeframe

End point values	NR: Bari 2 mg to 2 mg	NR: Bari 2 mg to 4 mg	NR: Bari 4 mg to 4 mg
Number of subjects analysed	20	21	39
Units: Percentage of participants
number (confidence interval 95%)
Week 16	20.8 (8.1 to 41.6)	57.2 (36.5 to 75.5)	28.2 (16.5 to 43.8)
Week 36	25.0 (11.2 to 46.9)	28.6 (13.8 to 50.0)	23.1 (12.6 to 38.3)
Week 52	20.0 (8.1 to 41.6)	28.6 (13.8 to 50.0)	28.2 (16.5 to 43.8)

No statistical analyses for this end point

Secondary: RPR: Percentage of Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved 4-Point Improvement Itch Numeric Rating Scale (NRS)

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End point title

RPR: Percentage of Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved 4-Point Improvement 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 participants itching is indicated by selecting the number, using a daily diary, that best describes the worst level of itching in the past 24 hours. The results were analyzed using NRI. All participants who either discontinued the study treatment or discontinued the study for any reason at any time were defined as non-responders for the NRI analysis for categorical variables such as NRS. APD: Modified Intent-to-treat Population: All RPR participants who received at least one dose of IP in JAHN with Baseline Itch NRS Score >= 4. The participants here are from the previous Baricitinib monotherapy studies (JAHL and JAHM) as the results are presented as subsets of overall RPR population.

End point type

Secondary

End point timeframe

Week 16

End point values	RPR-Placebo	RPR-Bari 1-mg	RPR-Bari 2-mg	RPR-Bari 4-mg
Number of subjects analysed	43	31	43	61
Units: Percentage of participants
number (confidence interval 95%)	32.6 (20.5 to 47.5)	25.8 (13.7 to 43.2)	32.6 (20.5 to 47.5)	41.0 (29.5 to 53.5)

No statistical analyses for this end point

Secondary: RPR: Percentage of Participants From Combination Therapy Study (JAIY) Who Achieved 4-Point Improvement in Itch NRS

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End point title

RPR: Percentage of Participants From Combination Therapy Study (JAIY) Who Achieved 4-Point Improvement in Itch 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 participants itching is indicated by selecting the number, using a daily diary, that best describes the worst level of itching in the past 24 hours. The results were analyzed using NRI. All participants who either discontinued the study treatment or discontinued the study for any reason at any time were defined as non-responders for the NRI analysis for categorical variables such as NRS. APD: Modified Intent-to-treat Population: All RPR participants who received at least one dose of IP in JAHN with Baseline Itch NRS Score >= 4. The participants here are from the previous Baricitinib combination therapy study (JAIY) as the results are presented as subsets of overall RPR population.

End point type

Secondary

End point timeframe

Week 16

End point values	NR: Bari 2 mg to 2 mg	NR: Bari 2 mg to 4 mg	NR: Bari 4 mg to 4 mg
Number of subjects analysed	32	48	56
Units: Percentage of participants
number (confidence interval 95%)	37.5 (22.9 to 54.7)	45.8 (32.6 to 59.7)	46.4 (34.0 to 59.3)

No statistical analyses for this end point

Secondary: NR: Percentage of Baricitinib NR Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved 4-Point Improvement in Itch NRS

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End point title

NR: Percentage of Baricitinib NR Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved 4-Point Improvement in Itch 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 participants itching is indicated by selecting the number, using a daily diary, that best describes the worst level of itching in the past 24 hours. The results were analyzed using NRI. All participants who either discontinued the study treatment or discontinued the study for any reason at any time were defined as non-responders for the NRI analysis for categorical variables such as NRS. APD: Modified Intent-to-treat Population: All NR participants who received at least one dose of IP in JAHN with Baseline Itch NRS Score >= 4. The participants here are from previous Baricitinib monotherapy studies (JAHL and JAHM) as the results are presented as subsets of overall NR population.

End point type

Secondary

End point timeframe

Week 16

End point values	NR: Bari 1 mg to 2 mg	NR: Bari 1 mg to 4 mg	NR: Bari 2 mg to 2 mg	NR: Bari 2 mg to 4 mg	NR: Bari 4 mg to 4 mg
Number of subjects analysed	80	62	70	71	138
Units: Percentage of participants
number (confidence interval 95%)	20.0 (12.7 to 30.0)	38.7 (27.6 to 51.2)	24.3 (15.8 to 35.5)	31.0 (21.4 to 42.5)	22.5 (16.3 to 30.1)

No statistical analyses for this end point

Secondary: NR: Percentage of Baricitinib NR Participants From Combination Therapy Study (JAIY) Who Achieved 4-Point Improvement in Itch NRS

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End point title

NR: Percentage of Baricitinib NR Participants From Combination Therapy Study (JAIY) Who Achieved 4-Point Improvement in Itch 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 participants itching is indicated by selecting the number, using a daily diary, that best describes the worst level of itching in the past 24 hours. The results were analyzed using NRI. All participants who either discontinued the study treatment or discontinued the study for any reason at any time were defined as non-responders for the NRI analysis for categorical variables such as NRS. APD: Modified Intent-to-treat Population: All NR participants who received at least one dose of IP in JAHN with Baseline Itch NRS Score >= 4. The participants here are from previous the previous Baricitinib combination therapy study (JAIY) as the results are presented as subsets of overall NR population.

End point type

Secondary

End point timeframe

Week 16

End point values	NR: Bari 2 mg to 2 mg	NR: Bari 2 mg to 4 mg	NR: Bari 4 mg to 4 mg
Number of subjects analysed	19	19	35
Units: Percentage of participants
number (confidence interval 95%)	31.6 (15.4 to 54.0)	36.8 (19.1 to 59.0)	31.4 (18.6 to 48.0)

No statistical analyses for this end point

Secondary: NR: Percentage of Placebo NR Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved a Response of IGA 0, 1 or 2

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End point title

NR: Percentage of Placebo NR Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved a Response of IGA 0, 1 or 2

End point description

The IGA measures the investigator's global assessment of the participant's overall severity of their atopic dermatitis (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. The results were analyzed using NRI. All participants who either discontinued the study treatment or discontinued the study for any reason at any time were defined as non-responders for the NRI analysis for categorical variables such as IGA 0/1/2. APD: Modified Intent-to-treat Population: All NR participants who received at least one dose of IP in JAHN. The participants here are from previous the Baricitinib monotherapy studies (JAHL and JAHM) as the results are presented as subsets of overall NR population.

End point type

Secondary

End point timeframe

Weeks 4, 16, 24, 52

End point values	NR: Placebo to Bari 2 mg	NR: Placebo to Bari 4 mg
Number of subjects analysed	180	194
Units: Percentage of participants
number (confidence interval 95%)
Week 4	57.8 (50.5 to 64.8)	67.0 (60.1 to 73.2)
Week 16	56.7 (49.4 to 63.7)	62.9 (55.9 to 69.4)
Week 24	55.6 (48.3 to 62.6)	57.2 (50.2 to 64.0)
Week 52	50.6 (43.3 to 57.8)	46.9 (40.0 to 53.9)

No statistical analyses for this end point

Secondary: NR: Percentage of Placebo NR Participants From Combination Therapy Study (JAIY) Who Achieved a Response of IGA 0, 1 or 2

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End point title

NR: Percentage of Placebo NR Participants From Combination Therapy Study (JAIY) Who Achieved a Response of IGA 0, 1 or 2

End point description

The IGA measures the investigator's global assessment of the participant's overall severity of their atopic dermatitis (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. The results were analyzed using NRI. All participants who either discontinued the study treatment or discontinued the study for any reason at any time were defined as non-responders for the NRI analysis for categorical variables such as IGA 0/1/2. APD: Modified Intent-to-treat Population: All NR participants who received at least one dose of IP in JAHN. The participants here are from the previous Baricitinib combination therapy study (JAIY) as the results are presented as subsets of overall NR population.

End point type

Secondary

End point timeframe

Weeks 4, 16, 24, 52

End point values	NR: Placebo to Bari 2 mg	NR: Placebo to Bari 4 mg
Number of subjects analysed	34	28
Units: Percentage of participants
number (confidence interval 95%)
Week 4	50.0 (34.1 to 65.9)	46.4 (29.5 to 64.2)
Week 16	47.1 (31.5 to 63.3)	46.4 (29.5 to 64.2)
Week 24	38.2 (23.9 to 55.0)	39.3 (23.6 to 57.6)
Week 52	26.5 (14.6 to 43.1)	25.0 (12.7 to 43.4)

No statistical analyses for this end point

Secondary: NR: Percentage of Placebo NR Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved a Response of IGA 0 or 1

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End point title

NR: Percentage of Placebo NR Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved a Response of IGA 0 or 1

End point description

The IGA measures the investigator's global assessment of the participant's overall severity of their atopic dermatitis (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. The results were analyzed using NRI. All participants who either discontinued the study treatment or discontinued the study for any reason at any time were defined as non-responders for the NRI analysis for categorical variables such as IGA 0/1. APD: Modified Intent-to-treat Population: All NR participants who received at least one dose of IP in JAHN. The participants here are from previous the Baricitinib monotherapy studies (JAHL and JAHM) as the results are presented as subsets of overall NR population.

End point type

Secondary

End point timeframe

Weeks 4, 16, 24, 52

End point values	NR: Placebo to Bari 2 mg	NR: Placebo to Bari 4 mg
Number of subjects analysed	180	194
Units: Percentage of participants
number (confidence interval 95%)
Week 4	22.8 (17.3 to 29.4)	25.8 (20.1 to 32.4)
Week 16	22.2 (16.8 to 28.8)	29.9 (23.9 to 36)
Week 24	22.2 (16.8 to 28.8)	27.8 (22.0 to 34.5)
Week 52	20.6 (15.3 to 27.0)	23.7 (18.3 to 30.2)

No statistical analyses for this end point

Secondary: NR: Percentage of Placebo NR Participants From Combination Therapy Study (JAIY) Who Achieved a Response of IGA 0 or 1

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End point title

NR: Percentage of Placebo NR Participants From Combination Therapy Study (JAIY) Who Achieved a Response of IGA 0 or 1

End point description

The IGA measures the investigator's global assessment of the participant's overall severity of their atopic dermatitis (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. The results were analyzed using NRI. All participants who either discontinued the study treatment or discontinued the study for any reason at any time were defined as non-responders for the NRI analysis for categorical variables such as IGA 0/1. APD: Modified Intent-to-treat Population: All NR participants who received at least one dose of IP in JAHN. The participants here are from previous the previous Baricitinib combination therapy study (JAIY) as the results are presented as subsets of overall NR population.

End point type

Secondary

End point timeframe

Weeks 4, 16, 24, 52

End point values	NR: Placebo to Bari 2 mg	NR: Placebo to Bari 4 mg
Number of subjects analysed	34	28
Units: Percentage of participants
number (confidence interval 95%)
Week 4	0 (0.0 to 10.2)	14.3 (5.7 to 31.5)
Week 16	5.9 (1.6 to 19.1)	25.0 (12.7 to 43.4)
Week 24	11.8 (4.7 to 26.6)	17.9 (7.9 to 35.6)
Week 52	5.9 (1.6 to 19.1)	10.7 (3.7 to 27.2)

No statistical analyses for this end point

Secondary: NR: Percentage of Placebo NR Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved a Response of EASI 75

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End point title

NR: Percentage of Placebo NR Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved a Response of EASI 75

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 to 72 (severe). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score. APD: Modified Intent-to-treat Population: All NR participants who received at least one dose of IP in JAHN. The participants here are from previous the Baricitinib monotherapy studies (JAHL and JAHM) as the results are presented as subsets of overall NR population.

End point type

Secondary

End point timeframe

Weeks 4, 16, 24, 52 Results were analyzed using NRI. Participants who either discontinued study treatment or discontinued the study for any reason at any time were defined as non-responders for the NRI analysis for categorical variables such as EASI 75.

End point values	NR: Placebo to Bari 2 mg	NR: Placebo to Bari 4 mg
Number of subjects analysed	180	194
Units: Percentage of participants
number (confidence interval 95%)
Week 4	38.9 (32.1 to 46.2)	46.9 (40.0 to 53.9)
Week 16	43.9 (36.8 to 51.2)	53.6 (46.6 to 60.5)
Week 24	45.0 (37.9 to 52.3)	45.4 (38.5 to 52.4)
Week 52	41.1 (34.2 to 48.4)	38.7 (32.1 to 45.7)

No statistical analyses for this end point

Secondary: NR: Percentage of Placebo NR Participants From Combination Therapy Study (JAIY) Who Achieved a Response of EASI 75

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End point title

NR: Percentage of Placebo NR Participants From Combination Therapy Study (JAIY) Who Achieved a Response of EASI 75

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). The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score. APD: Modified Intent-to-treat Population: All NR participants who received at least one dose of IP in JAHN. The participants here are from the previous Baricitinib combination therapy study (JAIY) as the results are presented as subsets of overall NR population.

End point type

Secondary

End point timeframe

End point values	NR: Placebo to Bari 2 mg	NR: Placebo to Bari 4 mg
Number of subjects analysed	34	28
Units: Percentage of participants
number (confidence interval 95%)
Week 4	23.5 (12.4 to 40.0)	39.3 (23.6 to 57.6)
Week 16	38.2 (23.9 to 55.0)	39.3 (23.6 to 57.6)
Week 24	32.4 (19.1 to 49.2)	32.1 (17.9 to 50.7)
Week 52	26.5 (14.6 to 43.1)	32.1 (17.9 to 50.7)

No statistical analyses for this end point

Secondary: NR: Percentage of Placebo NR Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved 4-Point Improvement in Itch NRS

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End point title

NR: Percentage of Placebo NR Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved 4-Point Improvement in Itch 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 participants itching is indicated by selecting the number, using a daily diary, that best describes the worst level of itching in the past 24 hours. The results were analyzed using NRI. All participants who either discontinued the study treatment or discontinued the study for any reason at any time were defined as non-responders for the NRI analysis for categorical variables such as NRS. APD: Modified Intent-to-treat Population: All NR participants who received at least one dose of IP in JAHN with Baseline Itch NRS Score >= 4. The participants here are from previous the Baricitinib monotherapy studies (JAHL and JAHM) as the results are presented as subsets of overall NR population.

End point type

Secondary

End point timeframe

Week 16

End point values	NR: Placebo to Bari 2 mg	NR: Placebo to Bari 4 mg
Number of subjects analysed	165	171
Units: Percentage of participants
number (confidence interval 95%)	33.9 (27.2 to 41.5)	35.7 (28.9 to 43.1)

No statistical analyses for this end point

Secondary: NR: Percentage of Placebo NR Participants From Combination Therapy Study (JAIY) Who Achieved 4-Point Improvement in Itch NRS

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End point title

NR: Percentage of Placebo NR Participants From Combination Therapy Study (JAIY) Who Achieved 4-Point Improvement in Itch 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 participants itching is indicated by selecting the number, using a daily diary, that best describes the worst level of itching in the past 24 hours. The results were analyzed using NRI. All participants who either discontinued the study treatment or discontinued the study for any reason at any time were defined as non-responders for the NRI analysis for categorical variables such as NRS. APD: Modified Intent-to-treat Population: All NR participants who received at least one dose of IP in JAHN with Baseline Itch NRS Score >= 4. The participants here are from previous the previous Baricitinib combination therapy study (JAIY) as the results are presented as subsets of overall NR population.

End point type

Secondary

End point timeframe

Week 16

End point values	NR: Placebo to Bari 2 mg	NR: Placebo to Bari 4 mg
Number of subjects analysed	34	26
Units: Percentage of participants
number (confidence interval 95%)	20.6 (10.3 to 36.8)	26.9 (13.7 to 46.1)

No statistical analyses for this end point

Secondary: Percentage of Participants Who Achieved a Response of IGA 0, 1, or 2 Assessed at 16 Weeks After Rerandomization (Week 68) and Week 104 in Randomized Withdrawal and Downtitration Substudy (All Participants Entering the Substudy)

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End point title

Percentage of Participants Who Achieved a Response of IGA 0, 1, or 2 Assessed at 16 Weeks After Rerandomization (Week 68) and Week 104 in Randomized Withdrawal and Downtitration Substudy (All Participants Entering the Substudy)

End point description

The IGA measures the investigator's global assessment of the participant's overall severity of their atopic dermatitis (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:Randomized Downtitration Withdrawal Substudy Population: All participants (including open-label participants) who are rerandomized at Week 52, entered the substudy, and received at least 1 dose of the IP in Period 2.

End point type

Secondary

End point timeframe

Weeks 68, 104

End point values	2 mg Bari to Placebo Substudy	2 mg Bari to 1 mg Bari Substudy	2 mg Bari to 2 mg Bari Substudy	4 mg Bari to Placebo Substudy	4 mg Bari to 2 mg Bari Substudy	4 mg Bari to 4 mg Bari Substudy
Number of subjects analysed	92	91	92	84	84	84
Units: Percentage of participants
number (confidence interval 95%)
Week 68	44.6 (34.8 to 54.7)	70.3 (60.3 to 78.7)	92.4 (85.1 to 96.3)	50.0 (39.5 to 60.5)	60.7 (50.0 to 70.5)	86.9 (78.1 to 92.5)
Week 104	33.7 (24.9 to 43.8)	58.2 (48.0 to 67.8)	83.7 (74.8 to 89.9)	41.7 (31.7 to 52.3)	48.8 (38.4 to 59.3)	85.7 (76.7 to 91.6)

No statistical analyses for this end point

Secondary: Percentage of Participants Who Achieved a Response of IGA 0 or 1 Assessed at 16 Weeks After Rerandomization (Week 68) and Week 104 in Randomized Withdrawal and Downtitration substudy (All Participants Entering the Substudy)

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End point title

Percentage of Participants Who Achieved a Response of IGA 0 or 1 Assessed at 16 Weeks After Rerandomization (Week 68) and Week 104 in Randomized Withdrawal and Downtitration substudy (All Participants Entering the Substudy)

End point description

The IGA measures the investigator's global assessment of the participant's overall severity of their atopic dermatitis (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: Randomized Downtitration Withdrawal Substudy Population: All participants (including open-label participants) who are rerandomized at Week 52, entered the substudy, and received at least 1 dose of the IP in Period 2.

End point type

Secondary

End point timeframe

Weeks 68, 104

End point values	2 mg Bari to Placebo Substudy	2 mg Bari to 1 mg Bari Substudy	2 mg Bari to 2 mg Bari Substudy	4 mg Bari to Placebo Substudy	4 mg Bari to 2 mg Bari Substudy	4 mg Bari to 4 mg Bari Substudy
Number of subjects analysed	92	91	91	84	84	84
Units: Percentage of participants
number (confidence interval 95%)
Week 68	25.0 (17.3 to 34.7)	41.8 (32.2 to 52.0)	47.8 (37.9 to 57.9)	29.8 (21.0 to 40.2)	45.2 (35.0 to 55.9)	51.2 (40.7 to 61.6)
Week 104	21.7 (14.5 to 31.2)	38.5 (29.1 to 48.7)	42.4 (32.8 to 52.6)	33.3 (24.2 to 43.9)	35.7 (26.3 to 46.4)	47.6 (37.3 to 58.2)

No statistical analyses for this end point

Secondary: Percentage of Participants Achieving Response of EASI75 From Baseline of Originating Study Assessed at 16 Weeks After Rerandomization (Week 68) and Week 104 in Randomized Withdrawal and Downtitration Substudy (All Participants Entering the Substudy)

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End point title

Percentage of Participants Achieving Response of EASI75 From Baseline of Originating Study Assessed at 16 Weeks After Rerandomization (Week 68) and Week 104 in Randomized Withdrawal and Downtitration Substudy (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 to 72 (severe). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score. The results were analyzed using NRI. All participants who either discontinued the study treatment or discontinued the study for any reason at any time were defined as non-responders for the NRI analysis for categorical variables such as EASI 75.

End point type

Secondary

End point timeframe

Weeks 68, 104 APD: Randomized Downtitration Withdrawal Substudy Population: All participants (including open-label participants) who are rerandomized at Week 52, entered the substudy, and received at least 1 dose of the IP in Period 2.

End point values	2 mg Bari to Placebo Substudy	2 mg Bari to 1 mg Bari Substudy	2 mg Bari to 2 mg Bari Substudy	4 mg Bari to Placebo Substudy	4 mg Bari to 2 mg Bari Substudy	4 mg Bari to 4 mg Bari Substudy
Number of subjects analysed	92	91	92	84	84	84
Units: Percentage of participants
number (confidence interval 95%)
Week 68	44.6 (34.8 to 54.7)	69.2 (59.1 to 77.8)	73.9 (64.1 to 81.8)	45.2 (35.0 to 55.9)	58.3 (47.7 to 68.3)	79.8 (70.0 to 87.0)
Week 104	43.5 (33.8 to 53.7)	58.2 (48.0 to 67.8)	72.8 (63.0 to 80.9)	41.7 (31.7 to 52.3)	58.3 (47.7 to 68.3)	73.8 (63.5 to 82.0)

No statistical analyses for this end point

Secondary: Time to Retreatment (Time to IGA ≥3) in Randomized Withdrawal and Down titration (All Participants Entering the Sub study)

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End point title

Time to Retreatment (Time to IGA ≥3) in Randomized Withdrawal and Down titration (All Participants Entering the Sub study)

End point description

Participants who entered the Substudy and relapsed with an IGA ≥3. APD: Participants who received at least one dose of study medication during Week 52 to Week 200 in Study JAHN, entered the randomized down titration withdrawal sub study and experienced relapse (IGA ≥3) from Week 52 up to Week 200.

End point type

Secondary

End point timeframe

Week 52 Up to Week 200

End point values	2 mg Bari to Placebo Substudy	2 mg Bari to 1 mg Bari Substudy	2 mg Bari to 2 mg Bari Substudy	4 mg Bari to Placebo Substudy	4 mg Bari to 2 mg Bari Substudy	4 mg Bari to 4 mg Bari Substudy
Number of subjects analysed	63	49	45	50	47	39
Units: Days
median (inter-quartile range (Q1-Q3))	30.0 (28.0 to 87.0)	61.0 (29.0 to 269.0)	169.0 (56.0 to 368.0)	29.5 (26.0 to 113.0)	56.0 (29.0 to 170.0)	117.0 (57.0 to 289.0)

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) and Week 104 in Randomized Withdrawal and Downtitration substudy (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) and Week 104 in Randomized Withdrawal and Downtitration substudy (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 atopic dermatitis (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: Randomized Downtitration Withdrawal Substudy Population with Week 52 IGA of 0 or 1: All participants (including open-label participants) who are rerandomized at Week 52, entered the substudy with IGA 0 or 1, and received at least 1 dose of the IP in Period 2.

End point type

Secondary

End point timeframe

Weeks 68, 104

End point values	2 mg Bari to Placebo Substudy	2 mg Bari to 1 mg Bari Substudy	2 mg Bari to 2 mg Bari Substudy	4 mg Bari to Placebo Substudy	4 mg Bari to 2 mg Bari Substudy	4 mg Bari to 4 mg Bari Substudy
Number of subjects analysed	49	48	48	43	43	43
Units: Percentage of participants
number (confidence interval 95%)
Week 68	55.1 (41.3 to 68.1)	89.6 (77.8 to 95.5)	95.8 (86.0 to 98.8)	72.1 (57.3 to 83.3)	76.7 (62.3 to 86.8)	97.7 (87.9 to 99.6)
Week 104	42.9 (30.0 to 56.7)	77.1 (63.5 to 86.7)	93.8 (83.2 to 97.9)	62.8 (47.9 to 75.6)	69.8 (54.9 to 81.4)	90.7 (78.4 to 96.3)

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) and Week 104 in Randomized Withdrawal and Downtitration Substudy (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) and Week 104 in Randomized Withdrawal and Downtitration Substudy (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 atopic dermatitis (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: Randomized Downtitration Withdrawal Substudy Population with Week 52 IGA of 0 or 1: All participants (including open-label participants) who are rerandomized at Week 52, entered the substudy with IGA 0 or 1, and received at least 1 dose of the IP in Period 2.

End point type

Secondary

End point timeframe

Weeks 68, 104

End point values	2 mg Bari to Placebo Substudy	2 mg Bari to 1 mg Bari Substudy	2 mg Bari to 2 mg Bari Substudy	4 mg Bari to Placebo Substudy	4 mg Bari to 2 mg Bari Substudy	4 mg Bari to 4 mg Bari Substudy
Number of subjects analysed	49	48	48	43	43	43
Units: Percentage of participants
number (confidence interval 95%)
Week 68	36.7 (24.7 to 50.7)	66.7 (52.5 to 78.3)	70.8 (56.8 to 81.8)	55.8 (41.1 to 69.6)	69.8 (54.9 to 81.4)	74.4 (59.8 to 85.1)
Week 104	32.7 (21.2 to 46.6)	60.4 (46.3 to 73.0)	60.4 (46.3 to 73.0)	58.1 (43.3 to 71.6)	55.8 (41.1 to 69.6)	62.8 (47.9 to 75.6)

No statistical analyses for this end point

Secondary: Percentage of participants with a response of EASI75 from baseline of originating study assessed at 16 weeks after rerandomization (Week 68) and Week 104 Randomized Withdrawal and Downtitration Substudy (Participants Entering the Substudy with IGA 0 or 1)

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End point title

Percentage of participants with a response of EASI75 from baseline of originating study assessed at 16 weeks after rerandomization (Week 68) and Week 104 Randomized Withdrawal and Downtitration Substudy (Participants Entering the Substudy with IGA 0 or 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. APD:Randomized Downtitration Withdrawal Substudy Population with Week 52 IGA of 0 or 1: All participants (including open-label participants) who are rerandomized at Week 52, entered the substudy with IGA 0 or 1, and received at least 1 dose of the IP in Period 2.

End point type

Secondary

End point timeframe

Weeks 68, 104

End point values	2 mg Bari to Placebo Substudy	2 mg Bari to 1 mg Bari Substudy	2 mg Bari to 2 mg Bari Substudy	4 mg Bari to Placebo Substudy	4 mg Bari to 2 mg Bari Substudy	4 mg Bari to 4 mg Bari Substudy
Number of subjects analysed	49	48	48	43	43	43
Units: Percentage of participants
number (confidence interval 95%)
Week 68	63.3 (49.3 to 75.3)	89.6 (77.8 to 95.5)	83.3 (70.4 to 91.3)	72.1 (57.3 to 83.3)	76.7 (62.3 to 86.8)	93 (81.4 to 97.6)
Week 104	55.1 (41.3 to 68.1)	79.2 (65.7 to 88.3)	83.3 (70.4 to 91.3)	67.4 (52.5 to 79.5)	74.4 (59.8 to 85.1)	76.7 (62.3 to 86.8)

No statistical analyses for this end point

Secondary: Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed Within 16 weeks of Retreatment (Week 68) Randomized Withdrawal and Downtitration (Participants Retreated During Substudy)

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End point title

Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed Within 16 weeks of Retreatment (Week 68) Randomized Withdrawal and Downtitration (Participants Retreated During 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:Re-Treatment Substudy Population: A subset of Randomized Downtitration Withdrawal Substudy Population who experienced IGA ≥3 at any time in Period 2 and received at least 1 dose of retreatment of the original dose.

End point type

Secondary

End point timeframe

Week 68

End point values	2 mg Bari to Placebo Substudy	2 mg Bari to 1 mg Bari Substudy	2 mg Bari to 2 mg Bari Substudy	4 mg Bari to Placebo Substudy	4 mg Bari to 2 mg Bari Substudy	4 mg Bari to 4 mg Bari Substudy
Number of subjects analysed	63	45	49	50	47	39
Units: Percentage of participants
number (not applicable)	76.2	55.6	57.1	80.0	74.5	69.2

No statistical analyses for this end point

Secondary: Percentage of participants with a response of IGA 0 or 1 Assessed Within 16 weeks of Retreatment (Week 68) Randomized Withdrawal and Downtitration (Participants Retreated During Substudy)

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End point title

Percentage of participants with a response of IGA 0 or 1 Assessed Within 16 weeks of Retreatment (Week 68) Randomized Withdrawal and Downtitration (Participants Retreated During Substudy)

End point description

The IGA measures the investigator's global assessment of the participant's overall severity of their atopic dermatitis (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: Re-Treatment Substudy Population: A subset of Randomized Downtitration Withdrawal Substudy Population who experienced IGA ≥3 at any time in Period 2 and received at least 1 dose of retreatment of the original dose.

End point type

Secondary

End point timeframe

Week 68

End point values	2 mg Bari to Placebo Substudy	2 mg Bari to 1 mg Bari Substudy	2 mg Bari to 2 mg Bari Substudy	4 mg Bari to Placebo Substudy	4 mg Bari to 2 mg Bari Substudy	4 mg Bari to 4 mg Bari Substudy
Number of subjects analysed	63	45	49	50	47	39
Units: Percentage of participants
number (not applicable)	39.7	26.7	10.2	44.0	25.5	23.1

No statistical analyses for this end point

Secondary: Percentage of Participants Achieving Response of EASI75 from Baseline of Originating Study Assessed Within 16 Weeks of Retreatment (Week 68) Randomized Withdrawal and Downtitration (Participants Retreated During Substudy)

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End point title

Percentage of Participants Achieving Response of EASI75 from Baseline of Originating Study Assessed Within 16 Weeks of Retreatment (Week 68) Randomized Withdrawal and Downtitration (Participants Retreated During 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: Re-Treatment Substudy Population: A subset of Randomized Downtitration Withdrawal Substudy Population who experienced IGA ≥3 at any time in Period 2 and received at least 1 dose of retreatment of the original dose.

End point type

Secondary

End point timeframe

Week 68

End point values	2 mg Bari to Placebo Substudy	2 mg Bari to 1 mg Bari Substudy	2 mg Bari to 2 mg Bari Substudy	4 mg Bari to Placebo Substudy	4 mg Bari to 2 mg Bari Substudy	4 mg Bari to 4 mg Bari Substudy
Number of subjects analysed	63	45	49	50	47	39
Units: Percentage of participants
number (not applicable)	71.4	44.4	55.1	70.0	53.2	61.5

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

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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

End point description

The IGA measures the investigator's global assessment of the participant's overall severity of their atopic dermatitis (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: Period 2 Nonsubstudy Population: All participants randomized at Week 0 of main Study JAHN (excluding open-label participants) who were not eligible to enter the substudy at Week 52 and received at least 1 dose of the IP in Period 2

End point type

Secondary

End point timeframe

Week 104

End point values	Placebo to Placebo Non-substudy	1 mg Bari to 1 mg Bari Non-substudy	2 mg Bari to 2 mg Bari Non-substudy	4 mg Bari to 4 mg Bari Non-substudy
Number of subjects analysed	70	32	193	264
Units: Percentage of participants
number (confidence interval 95%)	51.4 (40.0 to 62.8)	71.9 (54.6 to 84.4)	45.6 (38.7 to 52.6)	41.3 (35.5 to 47.3)

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

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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

End point description

The IGA measures the investigator's global assessment of the participant's overall severity of their atopic dermatitis (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. 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: Period 2 Nonsubstudy Population: All participants randomized at Week 0 of main Study JAHN (excluding open-label participants) who were not eligible to enter the substudy at Week 52 and received at least 1 dose of the IP in Period 2

End point type

Secondary

End point timeframe

Week 104

End point values	Placebo to Placebo Non-substudy	1 mg Bari to 1 mg Bari Non-substudy	2 mg Bari to 2 mg Bari Non-substudy	4 mg Bari to 4 mg Bari Non-substudy
Number of subjects analysed	70	32	193	264
Units: Percentage of participants
number (confidence interval 95%)	40.0 (29.3 to 51.7)	53.1 (36.4 to 69.1)	13.5 (9.4 to 19.0)	13.3 (9.7 to 17.9)

No statistical analyses for this end point

Secondary: Percentage of Participants Achieving Response of EASI75 from Baseline of Originating Study Assessed at Week 104 Participants Not Entered Into Substudy

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End point title

Percentage of Participants Achieving Response of EASI75 from Baseline of Originating Study Assessed at Week 104 Participants Not Entered Into 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: Period 2 Nonsubstudy Population: All participants randomized at Week 0 of main Study JAHN (excluding open-label participants) who were not eligible to enter the substudy at Week 52 and received at least 1 dose of the IP in Period 2

End point type

Secondary

End point timeframe

Week 104

End point values	Placebo to Placebo Non-substudy	1 mg Bari to 1 mg Bari Non-substudy	2 mg Bari to 2 mg Bari Non-substudy	4 mg Bari to 4 mg Bari Non-substudy
Number of subjects analysed	70	32	193	264
Units: Percentage of participants
number (confidence interval 95%)	54.3 (42.7 to 65.4)	65.6 (48.3 to 79.6)	40.9 (34.2 to 48.0)	39.8 (34.1 to 45.8)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Baseline through Week 200

Adverse event reporting additional description

All participants who received at least one dose of IP. The participants from open label arm were included in the Baricitinib 2-mg arm while reporting the safety data. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

26.0

Reporting group title

Placebo

Reporting group description

Participants from previous Baricitinib monotherapy studies (JAHL, JAHM) and combination therapy study (JAIY) were randomized or assigned to this arm to receive placebo orally.

Reporting group title

Bari 1-mg

Reporting group description

Participants from previous Baricitinib monotherapy studies (JAHL, JAHM) were randomized or assigned to this arm to receive Baricitinib 1 mg orally.

Reporting group title

Bari 2-mg

Reporting group description

Participants from previous Baricitinib monotherapy studies (JAHL, JAHM) and combination study (JAIY) were randomized or assigned to this arm to receive Baricitinib 2 mg orally.

Reporting group title

Bari 4-mg

Reporting group description

Participants from previous Baricitinib monotherapy studies (JAHL, JAHM) and combination study (JAIY) were randomized or assigned to this arm to receive Baricitinib 4 mg orally.

Reporting group title

2 mg Bari to Placebo Substudy

Reporting group description

Participants who received Baricitinib 2 mg at the start of Study JAHN were rerandomized at week 52 or assigned to this arm to receive placebo orally.

Reporting group title

2 mg Bari to 1 mg Bari Substudy

Reporting group description

Participants who received Baricitinib 2 mg at the start of Study JAHN were rerandomized at week 52 or assigned to this arm to receive Baricitinib 1 mg orally.

Reporting group title

4 mg Bari to 4 mg Bari Non-substudy

Reporting group description

Participants who received Baricitinib 4 mg at the start of Study JAHN who were not eligible to enter the substudy at week 52 assigned to this arm to receive Baricitinib 4 mg orally.

Reporting group title

4 mg Bari to Placebo Substudy

Reporting group description

Participants who received Baricitinib 4 mg at the start of Study JAHN were rerandomized at week 52 or assigned to this arm to receive placebo orally.

Reporting group title

4 mg Bari to 2 mg Bari Substudy

Reporting group description

Participants who received Baricitinib 4 mg at the start of Study JAHN were rerandomized at week 52 or assigned to this arm to receive Baricitinib 2 mg orally.

Reporting group title

4 mg Bari to 4 mg Bari Substudy

Reporting group description

Participants who received Baricitinib 4 mg at the start of Study JAHN were rerandomized at week 52 or assigned to this arm to receive Baricitinib 4 mg orally.

Reporting group title

Placebo to Placebo Non-substudy

Reporting group description

Participants who received placebo at the start of Study JAHN who were not eligible to enter the substudy at week 52 assigned to this arm to receive placebo orally.

Reporting group title

1 mg Bari to 1 mg Bari Non-substudy

Reporting group description

Participants who received Baricitinib 1 mg at the start of Study JAHN who were not eligible to enter the substudy at week 52 assigned to this arm to receive Baricitinib 1 mg orally.

Reporting group title

2 mg Bari to 2 mg Bari Non-substudy

Reporting group description

Participants who received Baricitinib 2 mg at the start of Study JAHN who were not eligible to enter the substudy at week 52 assigned to this arm to receive Baricitinib 2 mg orally.

Reporting group title

2 mg Bari to 2 mg Bari Substudy

Reporting group description

Participants who received Baricitinib 2 mg at the start of Study JAHN were rerandomized at week 52 or assigned to this arm to receive Baricitinib 2 mg orally.

Placebo

Bari 1-mg

Bari 2-mg

Bari 4-mg

2 mg Bari to Placebo Substudy

2 mg Bari to 1 mg Bari Substudy

4 mg Bari to 4 mg Bari Non-substudy

4 mg Bari to Placebo Substudy

4 mg Bari to 2 mg Bari Substudy

4 mg Bari to 4 mg Bari Substudy

Placebo to Placebo Non-substudy

1 mg Bari to 1 mg Bari Non-substudy

2 mg Bari to 2 mg Bari Non-substudy

2 mg Bari to 2 mg Bari Substudy

Total subjects affected by serious adverse events

subjects affected / exposed

5 / 91 (5.49%)

1 / 45 (2.22%)

32 / 766 (4.18%)

40 / 743 (5.38%)

2 / 92 (2.17%)

1 / 91 (1.10%)

25 / 264 (9.47%)

3 / 84 (3.57%)

1 / 84 (1.19%)

11 / 84 (13.10%)

1 / 70 (1.43%)

3 / 32 (9.38%)

16 / 249 (6.43%)

3 / 92 (3.26%)

number of deaths (all causes)

number of deaths resulting from adverse events

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

anaplastic large cell lymphoma t- and null-cell types

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

1 / 743 (0.13%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

angiocentric lymphoma

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

1 / 84 (1.19%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

bladder neoplasm

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

1 / 766 (0.13%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

breast cancer stage ii

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

1 / 84 (1.19%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

colon neoplasm

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

1 / 84 (1.19%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

diffuse large b-cell lymphoma

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

1 / 264 (0.38%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

follicular lymphoma

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

1 / 249 (0.40%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

hodgkin's disease

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

1 / 84 (1.19%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

peripheral t-cell lymphoma unspecified

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

1 / 264 (0.38%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (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 26.0

subjects affected / exposed ^[1]

0 / 47 (0.00%)

0 / 29 (0.00%)

0 / 448 (0.00%)

0 / 504 (0.00%)

0 / 48 (0.00%)

0 / 61 (0.00%)

0 / 190 (0.00%)

0 / 48 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 36 (0.00%)

0 / 20 (0.00%)

1 / 159 (0.63%)

0 / 49 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

rectal cancer

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

1 / 766 (0.13%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (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 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

1 / 743 (0.13%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

testis cancer

alternative dictionary used: MedDRA 26.0

subjects affected / exposed ^[2]

0 / 47 (0.00%)

0 / 29 (0.00%)

0 / 448 (0.00%)

0 / 504 (0.00%)

0 / 48 (0.00%)

0 / 61 (0.00%)

0 / 190 (0.00%)

0 / 48 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 36 (0.00%)

1 / 20 (5.00%)

0 / 159 (0.00%)

0 / 49 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

uterine leiomyoma

alternative dictionary used: MedDRA 26.0

subjects affected / exposed ^[3]

0 / 44 (0.00%)

0 / 16 (0.00%)

0 / 318 (0.00%)

0 / 239 (0.00%)

0 / 44 (0.00%)

0 / 30 (0.00%)

1 / 74 (1.35%)

0 / 36 (0.00%)

0 / 30 (0.00%)

0 / 31 (0.00%)

0 / 34 (0.00%)

0 / 12 (0.00%)

0 / 90 (0.00%)

0 / 43 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

xanthogranuloma

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

1 / 84 (1.19%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

deep vein thrombosis

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

1 / 84 (1.19%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

thrombophlebitis

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

2 / 743 (0.27%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

vasculitis

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

1 / 743 (0.13%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Surgical and medical procedures

wisdom teeth removal

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

1 / 249 (0.40%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pregnancy, puerperium and perinatal conditions

ectopic pregnancy

alternative dictionary used: MedDRA 26.0

subjects affected / exposed ^[4]

0 / 44 (0.00%)

0 / 16 (0.00%)

0 / 318 (0.00%)

0 / 239 (0.00%)

0 / 44 (0.00%)

0 / 30 (0.00%)

0 / 74 (0.00%)

0 / 36 (0.00%)

0 / 30 (0.00%)

0 / 31 (0.00%)

0 / 34 (0.00%)

0 / 12 (0.00%)

1 / 90 (1.11%)

0 / 43 (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

chest pain

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

1 / 264 (0.38%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

death

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

1 / 264 (0.38%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (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

Immune system disorders

anaphylactic reaction

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

1 / 766 (0.13%)

0 / 743 (0.00%)

1 / 92 (1.09%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (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

Reproductive system and breast disorders

uterine haemorrhage

alternative dictionary used: MedDRA 26.0

subjects affected / exposed ^[5]

1 / 44 (2.27%)

0 / 16 (0.00%)

0 / 318 (0.00%)

0 / 239 (0.00%)

0 / 44 (0.00%)

0 / 30 (0.00%)

0 / 74 (0.00%)

0 / 36 (0.00%)

0 / 30 (0.00%)

0 / 31 (0.00%)

0 / 34 (0.00%)

0 / 12 (0.00%)

0 / 90 (0.00%)

0 / 43 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

asthma

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

2 / 249 (0.80%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

epistaxis

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

1 / 743 (0.13%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pulmonary embolism

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

1 / 743 (0.13%)

0 / 92 (0.00%)

0 / 91 (0.00%)

1 / 264 (0.38%)

0 / 84 (0.00%)

1 / 84 (1.19%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (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

pulmonary hypertension

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

1 / 84 (1.19%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (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 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

2 / 264 (0.76%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Investigations

eosinophil count increased

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

1 / 264 (0.38%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (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 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

1 / 766 (0.13%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

1 / 84 (1.19%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (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

contusion

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

1 / 91 (1.10%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

concussion

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

1 / 84 (1.19%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

facial bones fracture

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

1 / 743 (0.13%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (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 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

1 / 766 (0.13%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

foot fracture

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

1 / 743 (0.13%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

meniscus injury

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

1 / 766 (0.13%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

limb injury

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

1 / 766 (0.13%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ligament sprain

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

1 / 766 (0.13%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

joint dislocation

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

1 / 766 (0.13%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

multiple injuries

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

1 / 766 (0.13%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pneumocephalus

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

1 / 91 (1.10%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

road traffic accident

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

1 / 743 (0.13%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

1 / 249 (0.40%)

0 / 92 (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

skull fractured base

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

1 / 91 (1.10%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

spinal fracture

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

1 / 249 (0.40%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

tibia fracture

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

1 / 743 (0.13%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Congenital, familial and genetic disorders

thyroglossal cyst

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

1 / 264 (0.38%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

cardiovascular disorder

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

1 / 70 (1.43%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

myocarditis

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

1 / 766 (0.13%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

myocardial infarction

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

1 / 84 (1.19%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

palpitations

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

1 / 264 (0.38%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

sinus tachycardia

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

1 / 743 (0.13%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ventricular extrasystoles

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

1 / 743 (0.13%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

brain stem haemorrhage

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

1 / 264 (0.38%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

brain stem infarction

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

1 / 84 (1.19%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

dizziness

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

1 / 743 (0.13%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

spinal cord haematoma

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

1 / 249 (0.40%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

subarachnoid haemorrhage

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

1 / 91 (1.10%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

autoimmune haemolytic anaemia

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

1 / 32 (3.13%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

hypochromic anaemia

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

1 / 249 (0.40%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ear and labyrinth disorders

haematotympanum

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

1 / 91 (1.10%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

tinnitus

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

1 / 743 (0.13%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Eye disorders

glaucoma

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

1 / 249 (0.40%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

open angle glaucoma

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

1 / 249 (0.40%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 4

0 / 0

deaths causally related to treatment / all

0 / 0

retinopathy proliferative

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

1 / 743 (0.13%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (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 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

1 / 743 (0.13%)

0 / 92 (0.00%)

0 / 91 (0.00%)

2 / 264 (0.76%)

0 / 84 (0.00%)

1 / 84 (1.19%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 3

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

anal fistula

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

1 / 264 (0.38%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

colitis

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

1 / 743 (0.13%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

dental cyst

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

1 / 249 (0.40%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

gastrointestinal haemorrhage

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

1 / 743 (0.13%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (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

intestinal obstruction

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

1 / 766 (0.13%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pancreatic failure

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

1 / 766 (0.13%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pancreatitis

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

1 / 766 (0.13%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

cholelithiasis

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

1 / 743 (0.13%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

drug-induced liver injury

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

1 / 91 (1.10%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

hepatic failure

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

1 / 766 (0.13%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Skin and subcutaneous tissue disorders

angioedema

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

1 / 92 (1.09%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

dermal cyst

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

1 / 249 (0.40%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

dermatitis atopic

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

1 / 91 (1.10%)

0 / 45 (0.00%)

10 / 766 (1.31%)

9 / 743 (1.21%)

0 / 92 (0.00%)

0 / 91 (0.00%)

5 / 264 (1.89%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

2 / 249 (0.80%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

3 / 13

5 / 11

0 / 0

1 / 5

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

dermatitis exfoliative

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

1 / 766 (0.13%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

parakeratosis

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

1 / 91 (1.10%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

urticaria

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

1 / 766 (0.13%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (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

acute kidney injury

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

1 / 249 (0.40%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

calculus urinary

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

1 / 743 (0.13%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

nephrolithiasis

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

1 / 92 (1.09%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

renal colic

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

1 / 743 (0.13%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

renal failure

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

1 / 766 (0.13%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

arthralgia

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

2 / 84 (2.38%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

bursitis

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

1 / 766 (0.13%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

compartment syndrome

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

1 / 743 (0.13%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

intervertebral disc protrusion

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

1 / 743 (0.13%)

0 / 92 (0.00%)

0 / 91 (0.00%)

1 / 264 (0.38%)

0 / 84 (0.00%)

1 / 70 (1.43%)

0 / 32 (0.00%)

1 / 249 (0.40%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

osteoarthritis

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

1 / 264 (0.38%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

osteonecrosis

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

1 / 743 (0.13%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (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

abscess jaw

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

1 / 766 (0.13%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

appendicitis

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

1 / 45 (2.22%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

1 / 92 (1.09%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

arthritis infective

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

1 / 743 (0.13%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

bacteraemia

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

1 / 766 (0.13%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

covid-19

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

1 / 249 (0.40%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

covid-19 pneumonia

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

1 / 91 (1.10%)

1 / 264 (0.38%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cellulitis

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

2 / 743 (0.27%)

0 / 92 (0.00%)

0 / 91 (0.00%)

4 / 264 (1.52%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

4 / 4

0 / 0

deaths causally related to treatment / all

0 / 0

diverticulitis

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

1 / 743 (0.13%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

endophthalmitis

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

1 / 743 (0.13%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

eczema herpeticum

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

2 / 766 (0.26%)

6 / 743 (0.81%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

5 / 6

0 / 0

deaths causally related to treatment / all

0 / 0

erysipelas

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

1 / 743 (0.13%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

erysipeloid

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

1 / 264 (0.38%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

hepatitis syphilitic

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

1 / 84 (1.19%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

influenza

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

1 / 766 (0.13%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

osteomyelitis

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

1 / 766 (0.13%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

otitis externa

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

1 / 743 (0.13%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

1 / 32 (3.13%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pelvic abscess

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

1 / 84 (1.19%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pneumonia

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

1 / 766 (0.13%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

postoperative wound infection

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

1 / 91 (1.10%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

psoas abscess

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

1 / 743 (0.13%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pyelonephritis

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

1 / 766 (0.13%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

sinusitis

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

1 / 743 (0.13%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

skin bacterial infection

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

1 / 766 (0.13%)

1 / 743 (0.13%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

staphylococcal bacteraemia

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

1 / 743 (0.13%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

staphylococcal skin infection

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

1 / 743 (0.13%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

superinfection bacterial

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

2 / 743 (0.27%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

syphilis

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

1 / 743 (0.13%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

varicella

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

0 / 766 (0.00%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

1 / 92 (1.09%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Metabolism and nutrition disorders

dairy intolerance

alternative dictionary used: MedDRA 26.0

subjects affected / exposed

0 / 91 (0.00%)

0 / 45 (0.00%)

1 / 766 (0.13%)

0 / 743 (0.00%)

0 / 92 (0.00%)

0 / 91 (0.00%)

0 / 264 (0.00%)

0 / 84 (0.00%)

0 / 70 (0.00%)

0 / 32 (0.00%)

0 / 249 (0.00%)

0 / 92 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 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 only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
[2] - 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 only occurring 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 to this adverse event. These numbers are expected to be equal.
Justification: Gender specific events only occurring 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 to this adverse event. These numbers are expected to be equal.
Justification: Gender specific events only occurring 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 to this adverse event. These numbers are expected to be equal.
Justification: Gender specific events only occurring 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	Bari 1-mg	Bari 2-mg	Bari 4-mg	2 mg Bari to Placebo Substudy	2 mg Bari to 1 mg Bari Substudy	4 mg Bari to 4 mg Bari Non-substudy	4 mg Bari to Placebo Substudy	4 mg Bari to 2 mg Bari Substudy	4 mg Bari to 4 mg Bari Substudy	Placebo to Placebo Non-substudy	1 mg Bari to 1 mg Bari Non-substudy	2 mg Bari to 2 mg Bari Non-substudy	2 mg Bari to 2 mg Bari Substudy
Total subjects affected by non serious adverse events
subjects affected / exposed	21 / 91 (23.08%)	14 / 45 (31.11%)	263 / 766 (34.33%)	268 / 743 (36.07%)	15 / 92 (16.30%)	27 / 91 (29.67%)	110 / 264 (41.67%)	16 / 84 (19.05%)	21 / 84 (25.00%)	42 / 84 (50.00%)	14 / 70 (20.00%)	14 / 32 (43.75%)	96 / 249 (38.55%)	38 / 92 (41.30%)
Investigations
alanine aminotransferase increased
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 91 (0.00%)	0 / 45 (0.00%)	13 / 766 (1.70%)	10 / 743 (1.35%)	0 / 92 (0.00%)	0 / 91 (0.00%)	6 / 264 (2.27%)	0 / 84 (0.00%)	0 / 84 (0.00%)	2 / 84 (2.38%)	1 / 70 (1.43%)	3 / 32 (9.38%)	4 / 249 (1.61%)	1 / 92 (1.09%)
occurrences all number	0	0	13	10	0	0	6	0	0	2	1	3	4	1
blood creatine phosphokinase increased
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 91 (0.00%)	1 / 45 (2.22%)	12 / 766 (1.57%)	18 / 743 (2.42%)	1 / 92 (1.09%)	1 / 91 (1.10%)	6 / 264 (2.27%)	0 / 84 (0.00%)	1 / 84 (1.19%)	5 / 84 (5.95%)	0 / 70 (0.00%)	0 / 32 (0.00%)	5 / 249 (2.01%)	4 / 92 (4.35%)
occurrences all number	0	1	13	18	1	1	6	0	1	6	0	0	5	5
hepatic enzyme increased
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 91 (1.10%)	0 / 45 (0.00%)	2 / 766 (0.26%)	2 / 743 (0.27%)	0 / 92 (0.00%)	0 / 91 (0.00%)	1 / 264 (0.38%)	0 / 84 (0.00%)	1 / 84 (1.19%)	2 / 84 (2.38%)	0 / 70 (0.00%)	2 / 32 (6.25%)	0 / 249 (0.00%)	0 / 92 (0.00%)
occurrences all number	1	0	2	2	0	0	1	0	1	2	0	2	0	0
Nervous system disorders
headache
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	6 / 91 (6.59%)	1 / 45 (2.22%)	46 / 766 (6.01%)	22 / 743 (2.96%)	3 / 92 (3.26%)	4 / 91 (4.40%)	10 / 264 (3.79%)	1 / 84 (1.19%)	1 / 84 (1.19%)	2 / 84 (2.38%)	3 / 70 (4.29%)	0 / 32 (0.00%)	14 / 249 (5.62%)	5 / 92 (5.43%)
occurrences all number	7	1	58	37	3	4	11	4	1	2	5	0	15	6
General disorders and administration site conditions
pyrexia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 91 (0.00%)	2 / 45 (4.44%)	17 / 766 (2.22%)	19 / 743 (2.56%)	0 / 92 (0.00%)	0 / 91 (0.00%)	4 / 264 (1.52%)	0 / 84 (0.00%)	1 / 84 (1.19%)	2 / 84 (2.38%)	2 / 70 (2.86%)	2 / 32 (6.25%)	7 / 249 (2.81%)	1 / 92 (1.09%)
occurrences all number	0	2	18	20	0	0	7	0	1	2	2	2	7	1
Skin and subcutaneous tissue disorders
dermal cyst
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 91 (0.00%)	0 / 45 (0.00%)	0 / 766 (0.00%)	4 / 743 (0.54%)	0 / 92 (0.00%)	0 / 91 (0.00%)	0 / 264 (0.00%)	0 / 84 (0.00%)	0 / 84 (0.00%)	2 / 84 (2.38%)	0 / 70 (0.00%)	2 / 32 (6.25%)	3 / 249 (1.20%)	1 / 92 (1.09%)
occurrences all number	0	0	0	4	0	0	0	0	0	3	0	2	3	1
urticaria
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 91 (1.10%)	0 / 45 (0.00%)	7 / 766 (0.91%)	14 / 743 (1.88%)	0 / 92 (0.00%)	1 / 91 (1.10%)	2 / 264 (0.76%)	1 / 84 (1.19%)	1 / 84 (1.19%)	0 / 84 (0.00%)	4 / 70 (5.71%)	1 / 32 (3.13%)	4 / 249 (1.61%)	1 / 92 (1.09%)
occurrences all number	1	0	8	19	0	1	2	1	1	0	4	1	5	1
Infections and infestations
covid-19
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 91 (0.00%)	0 / 45 (0.00%)	0 / 766 (0.00%)	0 / 743 (0.00%)	2 / 92 (2.17%)	9 / 91 (9.89%)	29 / 264 (10.98%)	7 / 84 (8.33%)	4 / 84 (4.76%)	14 / 84 (16.67%)	3 / 70 (4.29%)	7 / 32 (21.88%)	33 / 249 (13.25%)	14 / 92 (15.22%)
occurrences all number	0	0	0	0	2	9	31	8	5	15	4	7	33	15
folliculitis
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 91 (1.10%)	0 / 45 (0.00%)	19 / 766 (2.48%)	12 / 743 (1.62%)	0 / 92 (0.00%)	5 / 91 (5.49%)	6 / 264 (2.27%)	1 / 84 (1.19%)	0 / 84 (0.00%)	4 / 84 (4.76%)	1 / 70 (1.43%)	0 / 32 (0.00%)	10 / 249 (4.02%)	2 / 92 (2.17%)
occurrences all number	2	0	21	13	0	5	6	1	0	4	1	0	10	2
herpes zoster
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	2 / 91 (2.20%)	0 / 45 (0.00%)	13 / 766 (1.70%)	21 / 743 (2.83%)	0 / 92 (0.00%)	1 / 91 (1.10%)	26 / 264 (9.85%)	0 / 84 (0.00%)	2 / 84 (2.38%)	2 / 84 (2.38%)	0 / 70 (0.00%)	0 / 32 (0.00%)	13 / 249 (5.22%)	4 / 92 (4.35%)
occurrences all number	2	0	13	23	0	1	27	0	2	2	0	0	16	4
oral herpes
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	2 / 91 (2.20%)	0 / 45 (0.00%)	34 / 766 (4.44%)	40 / 743 (5.38%)	1 / 92 (1.09%)	0 / 91 (0.00%)	8 / 264 (3.03%)	1 / 84 (1.19%)	4 / 84 (4.76%)	2 / 84 (2.38%)	2 / 70 (2.86%)	0 / 32 (0.00%)	9 / 249 (3.61%)	4 / 92 (4.35%)
occurrences all number	3	0	47	51	2	0	9	7	5	2	3	0	14	4
nasopharyngitis
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	10 / 91 (10.99%)	9 / 45 (20.00%)	106 / 766 (13.84%)	122 / 743 (16.42%)	5 / 92 (5.43%)	3 / 91 (3.30%)	26 / 264 (9.85%)	6 / 84 (7.14%)	8 / 84 (9.52%)	11 / 84 (13.10%)	1 / 70 (1.43%)	1 / 32 (3.13%)	27 / 249 (10.84%)	10 / 92 (10.87%)
occurrences all number	12	15	140	173	6	3	32	12	9	14	1	1	30	14
urinary tract infection
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 91 (0.00%)	1 / 45 (2.22%)	20 / 766 (2.61%)	7 / 743 (0.94%)	1 / 92 (1.09%)	2 / 91 (2.20%)	5 / 264 (1.89%)	3 / 84 (3.57%)	6 / 84 (7.14%)	5 / 84 (5.95%)	1 / 70 (1.43%)	0 / 32 (0.00%)	3 / 249 (1.20%)	2 / 92 (2.17%)
occurrences all number	0	2	22	8	1	2	9	3	7	8	1	0	3	3
upper respiratory tract infection
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	3 / 91 (3.30%)	0 / 45 (0.00%)	43 / 766 (5.61%)	44 / 743 (5.92%)	4 / 92 (4.35%)	3 / 91 (3.30%)	10 / 264 (3.79%)	0 / 84 (0.00%)	2 / 84 (2.38%)	5 / 84 (5.95%)	1 / 70 (1.43%)	1 / 32 (3.13%)	11 / 249 (4.42%)	3 / 92 (3.26%)
occurrences all number	3	0	65	56	4	5	18	0	2	7	2	1	16	5
vulvovaginal candidiasis
alternative dictionary used: MedDRA 26.0
subjects affected / exposed ^[6]	0 / 44 (0.00%)	0 / 16 (0.00%)	4 / 318 (1.26%)	0 / 239 (0.00%)	0 / 44 (0.00%)	2 / 30 (6.67%)	0 / 74 (0.00%)	0 / 36 (0.00%)	0 / 30 (0.00%)	1 / 31 (3.23%)	0 / 34 (0.00%)	0 / 12 (0.00%)	0 / 90 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	6	0	0	3	0	0	0	1	0	0	0	1

Notes
[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 only occurring 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

27 Nov 2019

Substantial Amendment (c): - Included an additional six visits to reflect the 2-year extension to the study. - Updated discontinuation criteria for VTEs requiring permanent discontinuation after one VTE instead of two. - Added discontinuation criteria to reflect the possibility of study termination following potential approval or dismissal of Baricitinib for atopic dermatitis within a given country. - Removed leukotriene inhibitors and allergen immunotherapy from prohibited medications.

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

Clinical Trial Results: A Phase 3 Multicenter, Double-Blind Study to Evaluate the Long-Term Safety and Efficacy of Baricitinib in Adult Patients with Atopic Dermatitis

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Responder and Partial Responders (RPR): Percentage of Participants from Monotherapy Studies (JAHL, JAHM) who Achieved a Response of Investigator's Global Assessment (IGA) 0 or 1

Primary: Responder and Partial Responders (RPR): Percentage of Participants from Monotherapy Studies (JAHL, JAHM) who Achieved a Response of Investigator's Global Assessment (IGA) 0 or 1

Primary: RPR: Percentage of Participants from combination therapy study (JAIY) who achieved a response of IGA 0 or 1

Primary: RPR: Percentage of Participants from combination therapy study (JAIY) who achieved a response of IGA 0 or 1

Secondary: RPR: Percentage of Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved a Response of IGA 0, 1 or 2

Secondary: RPR: Percentage of Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved a Response of IGA 0, 1 or 2

Secondary: RPR: Percentage of Participants From Combination Therapy study (JAIY) Who Achieved a Response of IGA 0, 1, or 2

Secondary: RPR: Percentage of Participants From Combination Therapy study (JAIY) Who Achieved a Response of IGA 0, 1, or 2

Secondary: Non Responders (NR): Percentage of Baricitinib NR Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved a Response of IGA 0, 1 or 2

Secondary: Non Responders (NR): Percentage of Baricitinib NR Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved a Response of IGA 0, 1 or 2

Secondary: NR: Percentage of Baricitinib NR Participants From Combination Therapy Study (JAIY) Who Achieved a Response of IGA 0, 1 or 2

Secondary: NR: Percentage of Baricitinib NR Participants From Combination Therapy Study (JAIY) Who Achieved a Response of IGA 0, 1 or 2

Secondary: NR: Percentage of Baricitinib NR Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved a Response of IGA 0 or 1

Secondary: NR: Percentage of Baricitinib NR Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved a Response of IGA 0 or 1

Secondary: NR: Percentage of Baricitinib NR Participants From Combination Therapy Study (JAIY) Who Achieved a Response of IGA 0 or 1

Secondary: NR: Percentage of Baricitinib NR Participants From Combination Therapy Study (JAIY) Who Achieved a Response of IGA 0 or 1

Secondary: RPR: Percentage of Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved a Response of Eczema Area and Severity Index (EASI)75

Secondary: RPR: Percentage of Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved a Response of Eczema Area and Severity Index (EASI)75

Secondary: RPR: Percentage of Participants From Combination Therapy Study (JAIY) Who Achieved a Response of EASI 75

Secondary: RPR: Percentage of Participants From Combination Therapy Study (JAIY) Who Achieved a Response of EASI 75

Secondary: NR: Percentage of Baricitinib NR Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved a Response of EASI 75

Secondary: NR: Percentage of Baricitinib NR Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved a Response of EASI 75

Secondary: NR: Percentage of Baricitinib NR Participants From Combination Therapy Study (JAIY) Who Achieved a Response of EASI 75

Secondary: NR: Percentage of Baricitinib NR Participants From Combination Therapy Study (JAIY) Who Achieved a Response of EASI 75

Secondary: RPR: Percentage of Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved 4-Point Improvement Itch Numeric Rating Scale (NRS)

Secondary: RPR: Percentage of Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved 4-Point Improvement Itch Numeric Rating Scale (NRS)

Secondary: RPR: Percentage of Participants From Combination Therapy Study (JAIY) Who Achieved 4-Point Improvement in Itch NRS

Secondary: RPR: Percentage of Participants From Combination Therapy Study (JAIY) Who Achieved 4-Point Improvement in Itch NRS

Secondary: NR: Percentage of Baricitinib NR Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved 4-Point Improvement in Itch NRS

Secondary: NR: Percentage of Baricitinib NR Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved 4-Point Improvement in Itch NRS

Secondary: NR: Percentage of Baricitinib NR Participants From Combination Therapy Study (JAIY) Who Achieved 4-Point Improvement in Itch NRS

Secondary: NR: Percentage of Baricitinib NR Participants From Combination Therapy Study (JAIY) Who Achieved 4-Point Improvement in Itch NRS

Secondary: NR: Percentage of Placebo NR Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved a Response of IGA 0, 1 or 2

Secondary: NR: Percentage of Placebo NR Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved a Response of IGA 0, 1 or 2

Secondary: NR: Percentage of Placebo NR Participants From Combination Therapy Study (JAIY) Who Achieved a Response of IGA 0, 1 or 2

Secondary: NR: Percentage of Placebo NR Participants From Combination Therapy Study (JAIY) Who Achieved a Response of IGA 0, 1 or 2

Secondary: NR: Percentage of Placebo NR Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved a Response of IGA 0 or 1

Secondary: NR: Percentage of Placebo NR Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved a Response of IGA 0 or 1

Secondary: NR: Percentage of Placebo NR Participants From Combination Therapy Study (JAIY) Who Achieved a Response of IGA 0 or 1

Secondary: NR: Percentage of Placebo NR Participants From Combination Therapy Study (JAIY) Who Achieved a Response of IGA 0 or 1

Secondary: NR: Percentage of Placebo NR Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved a Response of EASI 75

Secondary: NR: Percentage of Placebo NR Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved a Response of EASI 75

Secondary: NR: Percentage of Placebo NR Participants From Combination Therapy Study (JAIY) Who Achieved a Response of EASI 75

Secondary: NR: Percentage of Placebo NR Participants From Combination Therapy Study (JAIY) Who Achieved a Response of EASI 75

Secondary: NR: Percentage of Placebo NR Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved 4-Point Improvement in Itch NRS

Secondary: NR: Percentage of Placebo NR Participants From Monotherapy Studies (JAHL, JAHM) Who Achieved 4-Point Improvement in Itch NRS

Secondary: NR: Percentage of Placebo NR Participants From Combination Therapy Study (JAIY) Who Achieved 4-Point Improvement in Itch NRS

Secondary: NR: Percentage of Placebo NR Participants From Combination Therapy Study (JAIY) Who Achieved 4-Point Improvement in Itch NRS

Secondary: Percentage of Participants Who Achieved a Response of IGA 0, 1, or 2 Assessed at 16 Weeks After Rerandomization (Week 68) and Week 104 in Randomized Withdrawal and Downtitration Substudy (All Participants Entering the Substudy)

Secondary: Percentage of Participants Who Achieved a Response of IGA 0, 1, or 2 Assessed at 16 Weeks After Rerandomization (Week 68) and Week 104 in Randomized Withdrawal and Downtitration Substudy (All Participants Entering the Substudy)

Secondary: Percentage of Participants Who Achieved a Response of IGA 0 or 1 Assessed at 16 Weeks After Rerandomization (Week 68) and Week 104 in Randomized Withdrawal and Downtitration substudy (All Participants Entering the Substudy)

Secondary: Percentage of Participants Who Achieved a Response of IGA 0 or 1 Assessed at 16 Weeks After Rerandomization (Week 68) and Week 104 in Randomized Withdrawal and Downtitration substudy (All Participants Entering the Substudy)

Secondary: Percentage of Participants Achieving Response of EASI75 From Baseline of Originating Study Assessed at 16 Weeks After Rerandomization (Week 68) and Week 104 in Randomized Withdrawal and Downtitration Substudy (All Participants Entering the Substudy)

Secondary: Percentage of Participants Achieving Response of EASI75 From Baseline of Originating Study Assessed at 16 Weeks After Rerandomization (Week 68) and Week 104 in Randomized Withdrawal and Downtitration Substudy (All Participants Entering the Substudy)

Secondary: Time to Retreatment (Time to IGA ≥3) in Randomized Withdrawal and Down titration (All Participants Entering the Sub study)

Secondary: Time to Retreatment (Time to IGA ≥3) in Randomized Withdrawal and Down titration (All Participants Entering the Sub study)

Secondary: Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed at 16 Weeks After Rerandomization (Week 68) and Week 104 in Randomized Withdrawal and Downtitration substudy (Participants Entering the Substudy With IGA 0 or 1)

Secondary: Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed at 16 Weeks After Rerandomization (Week 68) and Week 104 in Randomized Withdrawal and Downtitration substudy (Participants Entering the Substudy With IGA 0 or 1)

Secondary: Percentage of participants with a response of IGA 0 or 1 assessed at 16 weeks after rerandomization (Week 68) and Week 104 in Randomized Withdrawal and Downtitration Substudy (Participants Entering the Substudy with IGA 0 or 1)

Secondary: Percentage of participants with a response of IGA 0 or 1 assessed at 16 weeks after rerandomization (Week 68) and Week 104 in Randomized Withdrawal and Downtitration Substudy (Participants Entering the Substudy with IGA 0 or 1)

Secondary: Percentage of participants with a response of EASI75 from baseline of originating study assessed at 16 weeks after rerandomization (Week 68) and Week 104 Randomized Withdrawal and Downtitration Substudy (Participants Entering the Substudy with IGA 0 or 1)

Secondary: Percentage of participants with a response of EASI75 from baseline of originating study assessed at 16 weeks after rerandomization (Week 68) and Week 104 Randomized Withdrawal and Downtitration Substudy (Participants Entering the Substudy with IGA 0 or 1)

Secondary: Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed Within 16 weeks of Retreatment (Week 68) Randomized Withdrawal and Downtitration (Participants Retreated During Substudy)

Secondary: Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed Within 16 weeks of Retreatment (Week 68) Randomized Withdrawal and Downtitration (Participants Retreated During Substudy)

Secondary: Percentage of participants with a response of IGA 0 or 1 Assessed Within 16 weeks of Retreatment (Week 68) Randomized Withdrawal and Downtitration (Participants Retreated During Substudy)

Secondary: Percentage of participants with a response of IGA 0 or 1 Assessed Within 16 weeks of Retreatment (Week 68) Randomized Withdrawal and Downtitration (Participants Retreated During Substudy)

Secondary: Percentage of Participants Achieving Response of EASI75 from Baseline of Originating Study Assessed Within 16 Weeks of Retreatment (Week 68) Randomized Withdrawal and Downtitration (Participants Retreated During Substudy)

Secondary: Percentage of Participants Achieving Response of EASI75 from Baseline of Originating Study Assessed Within 16 Weeks of Retreatment (Week 68) Randomized Withdrawal and Downtitration (Participants Retreated During Substudy)

Secondary: Percentage of Participants with a response of IGA 0, 1, or 2 Assessed at Week 104 Participants Not Entered Into Substudy

Secondary: Percentage of Participants with a response of IGA 0, 1, or 2 Assessed at Week 104 Participants Not Entered Into Substudy

Clinical Trial Results:
A Phase 3 Multicenter, Double-Blind Study to Evaluate the Long-Term Safety and Efficacy of Baricitinib in Adult Patients with Atopic Dermatitis