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Clinical Trial Results:
A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL TO EVALUATE THE EFFICACY AND SAFETY OF LEBRIKIZUMAB IN PATIENTS WITH MODERATE-TO-SEVERE ATOPIC DERMATITIS

Summary
EudraCT number	2019-002932-10
Trial protocol	LT ES PL EE FR LV
Global end of trial date	03 May 2022

Results information
Results version number	v3(current)
This version publication date	15 Dec 2022
First version publication date	06 Jul 2022
Other versions	v1 , v2
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

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Sponsor protocol code

J2T-DM-KGAB, DRM06-AD04

ISRCTN number

US NCT number

NCT04146363

WHO universal trial number (UTN)

Other trial identifiers

Trial Number: 17801

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

03 May 2022

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

03 May 2022

Was the trial ended prematurely?

Main objective of the trial

The primary objective of this study is to evaluate the safety and efficacy of lebrikizumab compared with placebo in participants with moderate-to-severe atopic dermatitis.

Protection of trial subjects

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

Background therapy

Evidence for comparator

Actual start date of recruitment

24 Sep 2019

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Estonia: 8

Country: Number of subjects enrolled

France: 7

Country: Number of subjects enrolled

Latvia: 11

Country: Number of subjects enrolled

Lithuania: 18

Country: Number of subjects enrolled

Poland: 81

Country: Number of subjects enrolled

Australia: 39

Country: Number of subjects enrolled

Canada: 23

Country: Number of subjects enrolled

Korea, Republic of: 34

Country: Number of subjects enrolled

United States: 190

Country: Number of subjects enrolled

Spain: 13

Worldwide total number of subjects

424

EEA total number of subjects

138

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)

338

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Participants who did not achieve an Investigator Global Assessment (IGA) of 0 or 1 or EASI-75 at Week 16 and those participants who did not maintain an Eczema Area Severity Index (EASI)-50 response following re-randomization at Weeks 24, 32, 40, or 48 were assigned to an Escape Arm and received 250 mg Lebrikizumab as open-label Q2W through Week 52.

Screening details

Participants who did not achieve an EASI-50 response after 8 weeks in the Escape Arm were terminated from the study.

Period 1 title

Induction Period

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

Induction - Placebo (PBO)

Arm description

Induction Period (Baseline-Week 16): Two subcutaneous (SC) injections of Placebo as a loading dose at Baseline and Week 2 followed by a single injection every 2 weeks (Q2W) from Week 4 until Week 14.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Two subcutaneous (SC) injections of Placebo as a loading dose at Baseline and Week 2 followed by a single injection every 2 weeks (Q2W) from Week 4 until Week 14.

Induction - Lebrikizumab (Leb) Q2W

Arm description

Induction Period (Baseline-Week 16): 500 milligram (mg) Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 visits followed by a single 250 mg Lebrikizumab injection Q2W from Week 4 until Week 14.

Arm type

Experimental

Investigational medicinal product name

Lebrikizumab

Investigational medicinal product code

LY3650150

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

500 milligram (mg) Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 visits followed by a single 250 mg Lebrikizumab injection Q2W from Week 4 until Week 14.

Number of subjects in period 1	Induction - Placebo (PBO)	Induction - Lebrikizumab (Leb) Q2W
Started	141	283
Received at Least One Dose of Study Drug	141	282
Completed	120	263
Not completed	21	20
Positive quantiferon test	-	1
Adverse event, non-fatal	1	2
Due to Epidemic/Pandemic	1	2
Withdrawal by Subject	6	3
Lost to follow-up	1	4
Lack of efficacy	7	2
Protocol deviation	5	6

Period 2 title

Maintenance Blinded Treatment Period

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

Maintenance – Placebo Responder/Placebo

Arm description

Maintenance Secondary Population: Maintenance Period (Week 16 to Week 52): One SC injection of Placebo Q2W until Week 50. Two placebo SC injections as loading dose on Week 16 and Week 18.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

One SC injection of Placebo Q2W.

Maintenance - PBO Responder/Lebrikizumab 250 Q4W

Arm description

Maintenance Secondary Population: Maintenance Period (Week 16-Week 52): One 250 mg Lebrikizumab SC injection every 4 weeks (Q4W) on Weeks 20, 24, 28, 32, 36, 40, 44, and 48. One placebo SC injection Q4W on Weeks 22, 26, 30, 34, 38, 42, 46, and 50. For participants who received placebo in the Induction Period, the maintenance loading dose is: Two 250 mg Lebrikizumab SC injections on Week 16. Two placebo injections on Week 18.

Arm type

Experimental

Investigational medicinal product name

Lebrikizumab

Investigational medicinal product code

LY3650150

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

One 250 mg Lebrikizumab SC injection and one placebo SC injection as maintenance loading dose on Week 16 and two placebo SC injections on Week 18. One 250 mg Lebrikizumab SC injection Every 4 weeks (Q4W) on Weeks 20, 24, 28, 32, 36, 40, 44, and 48. One placebo SC injection Q4W on Weeks 22, 26, 30, 34, 38, 42, 46, and 50.

Maintenance – PBO Responder/Lebrikizumab 250 Q2W

Arm description

Maintenance Secondary Population: Maintenance Period (Week 16-Week 52): One 250 mg Lebrikizumab SC injection Q2W until Week 50. For participants who received placebo in the Induction Period, the maintenance loading dose is: Two 250 mg Lebrikizumab SC injections on Week 16. Two 250 mg Lebrikizumab SC injections on Week 18.

Arm type

Experimental

Investigational medicinal product name

Lebrikizumab

Investigational medicinal product code

LY3650150

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

250 mg Lebrikizumab SC injection Q2W.

Maintenance - Lebrikizumab Responder/Placebo

Arm description

Maintenance Primary Population: Maintenance Primary Population: Maintenance Period (Week 16 to Week 52): One SC injection of Placebo Q2W until Week 50. Two placebo SC injections as loading dose on Week 16 and Week 18.

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

One SC injection of Placebo Q2W.

Maintenance - Lebrikizumab Responder/Lebrikizumab 250 Q4W

Arm description

Maintenance Period (Week 16-Week 52): One 250 mg Lebrikizumab SC injection every 4 weeks (Q4W) on Weeks 20, 24, 28, 32, 36, 40, 44, and 48. One placebo SC injection Q4W on Weeks 22, 26, 30, 34, 38, 42, 46, and 50. To maintain the blind, for participants who received Lebrikizumab in the Induction Period, the maintenance loading dose is: One 250 mg Lebrikizumab SC injection and one placebo SC injection on Week 16. Two placebo injections on Week 18

Arm type

Experimental

Investigational medicinal product name

Lebrikizumab

Investigational medicinal product code

LY3650510

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Maintenance - Lebrikizumab Responder/Lebrikizumab 250 Q2W

Arm description

Maintenance Primary Population: Maintenance Period (Week 16-Week 52): One 250 mg Lebrikizumab SC injection Q2W until Week 50. To maintain the blind, for participants who received Lebrikizumab in the Induction Period, the maintenance loading dose is: One 250 mg Lebrikizumab SC injection and one placebo SC injection on Week 16. One 250 mg Lebrikizumab SC injection and one placebo SC injection on Week 18.

Arm type

Experimental

Investigational medicinal product name

Lebrikizumab

Investigational medicinal product code

LY3650510

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

250 mg Lebrikizumab SC injection Q2W.

Number of subjects in period 2 ^[1]	Maintenance – Placebo Responder/Placebo	Maintenance - PBO Responder/Lebrikizumab 250 Q4W	Maintenance – PBO Responder/Lebrikizumab 250 Q2W	Maintenance - Lebrikizumab Responder/Placebo	Maintenance - Lebrikizumab Responder/Lebrikizumab 250 Q4W	Maintenance - Lebrikizumab Responder/Lebrikizumab 250 Q2W
Started	4	10	10	32	63	62
Completed	2	10	9	22	54	48
Not completed	2	0	1	10	9	14
Physician decision	1	-	-	1	-	-
Adverse event, non-fatal	-	-	-	-	1	1
Withdrawal by Subject	-	-	1	2	3	5
Entered Escape Arm	1	-	-	7	4	6
Lost to follow-up	-	-	-	-	1	1
Lack of efficacy	-	-	-	-	-	1

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Participants who responded to treatment, defined as and IGA of 0 or 1 or a 75% reduction in EASI from baseline to Week 16, entered the Maintenance Period and re-randomized to the following treatment groups: lebrikizumab 250 mg Q2W, lebrikizumab 250 mg Q4W, or placebo Q2W.

Period 3 title

Maintenance Open Label (OL) Escape Arm

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Escape Arm Week 16 - Maintenance OL - PBO NR/Leb 250 Q2W

Arm description

Maintenance Escape Period (Week 16 to Week 52): Blinded loading doses based on prior treatment assignment will be administered, followed by one 250 mg Lebrikizumab SC injection Q2W until Week 50 in an open-label fashion. For participants who received placebo in the Induction Period, the loading dose is: Two 250 mg Lebrikizumab SC injection on Week 16. Two 250 mg Lebrikizumab SC injections on Week 18. For participants who do not maintain an acceptable response during the Maintenance Period and entered the Escape Arm, the loading doses will be administrated at entry and 2 weeks after entry based on the treatment assignment prior to entering escape arm. Participants who did not achieve an EASI-50 response after 8 weeks in the Escape Arm were terminated from the study.

Arm type

Experimental

Investigational medicinal product name

Lebrikizumab

Investigational medicinal product code

LY3650510

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

250 mg Lebrikizumab Q2W.

Escape Arm Week 16 - Maintenance OL - Leb NR/Leb 250 Q2W

Arm description

Maintenance Escape Period (Week 16 to Week 52): Blinded loading doses based on prior treatment assignment will be administered, followed by one 250 mg Lebrikizumab SC injection Q2W until Week 50 in an open-label fashion. To maintain the loading dose blind, for participants who received Lebrikizumab in the Induction Period, the loading dose is: One 250 mg Lebrikizumab SC injection and one placebo on Week16. One 250 mg Lebrikizumab SC injection and one placebo SC injection on Week 18. For participants who do not maintain an acceptable response during the Maintenance Period and entered the Escape Arm, the loading doses will be administrated at entry and 2 weeks after entry based on the treatment assignment prior to entering escape arm. Participants who did not achieve an EASI-50 response after 8 weeks in the Escape Arm were terminated from the study.

Arm type

Experimental

Investigational medicinal product name

Lebrikizumab

Investigational medicinal product code

LY3650510

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Maintenance Escape Period (Week 16 to Week 52): 250 mg Lebrikizumab SC injection Q2W.

Escape Arm Week 24 - 48 - Maintenance OL - Leb 250 Q2W

Arm description

Maintenance Escape Period (Week 24 to Week 48): One 250 mg Lebrikizumab SC injection Q2W.

Arm type

Experimental

Investigational medicinal product name

Lebrikizumab

Investigational medicinal product code

LY3650510

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Maintenance Escape Period (Week 24 to Week 48): 250 mg Lebrikizumab Q2W.

Number of subjects in period 3	Escape Arm Week 16 - Maintenance OL - PBO NR/Leb 250 Q2W	Escape Arm Week 16 - Maintenance OL - Leb NR/Leb 250 Q2W	Escape Arm Week 24 - 48 - Maintenance OL - Leb 250 Q2W
Started	96	106	18
Completed	77	77	15
Not completed	19	29	3
Physician decision	1	1	-
Adverse event, non-fatal	1	4	-
Pregnancy	-	1	-
Withdrawal by Subject	5	2	2
Lost to follow-up	1	2	-
EASI Scoring Error	-	2	-
Lack of efficacy	11	17	1

Baseline characteristics

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Reporting group title

Induction - Placebo (PBO)

Reporting group description

Induction Period (Baseline-Week 16): Two subcutaneous (SC) injections of Placebo as a loading dose at Baseline and Week 2 followed by a single injection every 2 weeks (Q2W) from Week 4 until Week 14.

Reporting group title

Induction - Lebrikizumab (Leb) Q2W

Reporting group description

Reporting group values	Induction - Placebo (PBO)	Induction - Lebrikizumab (Leb) Q2W	Total
Number of subjects	141	283	424
Age categorical
Units: Subjects
In utero	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0
Children (2-11 years)	0	0	0
Adolescents (12-17 years)	18	37	55
Adults (18-64 years)	113	225	338
From 65-84 years	10	19	29
85 years and over	0	2	2
Gender categorical
Units: Subjects
Female	73	141	214
Male	68	142	210
Race
Units: Subjects
American Indian or Alaska Native	0	7	7
Asian	31	39	70
Native Hawaiian or Other Pacific Islander	0	2	2
Black or African American	16	33	49
White	93	196	289
More than one race	1	4	5
Unknown or Not Reported	0	2	2
Region of Enrollment
Units: Subjects
Canada	7	16	23
South Korea	13	21	34
Latvia	6	5	11
United States	62	128	190
Poland	25	56	81
Australia	13	26	39
France	0	7	7
Lithuania	7	11	18
Spain	4	9	13
Estonia	4	4	8

End points

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Reporting group title

Induction - Placebo (PBO)

Reporting group description

Induction Period (Baseline-Week 16): Two subcutaneous (SC) injections of Placebo as a loading dose at Baseline and Week 2 followed by a single injection every 2 weeks (Q2W) from Week 4 until Week 14.

Reporting group title

Induction - Lebrikizumab (Leb) Q2W

Reporting group description

Reporting group title

Maintenance – Placebo Responder/Placebo

Reporting group description

Maintenance Secondary Population: Maintenance Period (Week 16 to Week 52): One SC injection of Placebo Q2W until Week 50. Two placebo SC injections as loading dose on Week 16 and Week 18.

Reporting group title

Maintenance - PBO Responder/Lebrikizumab 250 Q4W

Reporting group description

Reporting group title

Maintenance – PBO Responder/Lebrikizumab 250 Q2W

Reporting group description

Reporting group title

Maintenance - Lebrikizumab Responder/Placebo

Reporting group description

Reporting group title

Maintenance - Lebrikizumab Responder/Lebrikizumab 250 Q4W

Reporting group description

Reporting group title

Maintenance - Lebrikizumab Responder/Lebrikizumab 250 Q2W

Reporting group description

Reporting group title

Escape Arm Week 16 - Maintenance OL - PBO NR/Leb 250 Q2W

Reporting group description

Reporting group title

Escape Arm Week 16 - Maintenance OL - Leb NR/Leb 250 Q2W

Reporting group description

Maintenance Escape Period (Week 16 to Week 52): Blinded loading doses based on prior treatment assignment will be administered, followed by one 250 mg Lebrikizumab SC injection Q2W until Week 50 in an open-label fashion. To maintain the loading dose blind, for participants who received Lebrikizumab in the Induction Period, the loading dose is: One 250 mg Lebrikizumab SC injection and one placebo on Week16. One 250 mg Lebrikizumab SC injection and one placebo SC injection on Week 18. For participants who do not maintain an acceptable response during the Maintenance Period and entered the Escape Arm, the loading doses will be administrated at entry and 2 weeks after entry based on the treatment assignment prior to entering escape arm. Participants who did not achieve an EASI-50 response after 8 weeks in the Escape Arm were terminated from the study.

Reporting group title

Escape Arm Week 24 - 48 - Maintenance OL - Leb 250 Q2W

Reporting group description

Maintenance Escape Period (Week 24 to Week 48): One 250 mg Lebrikizumab SC injection Q2W.

Subject analysis set title

Escape Arm Week 24 - 48 - Maintenance OL - Leb 250 Q2W

Subject analysis set type

Sub-group analysis

Subject analysis set description

Escape Arm data included any participants from Induction Period entering the Escape Arm at W16 and participants in the Maintenance Period coming from Maintenance 250 mg Q2W dosing.

Primary: Percentage of Participants With an Investigator Global Assessment (IGA) Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 16

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End point title

Percentage of Participants With an Investigator Global Assessment (IGA) Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 16

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. Analysis Population Description (APD): All randomized participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. Markov Chain Monte Carlo Multiple Imputation (MCMC-MI) was used to handle missing data.

End point type

Primary

End point timeframe

Baseline to Week 16

End point values	Induction - Placebo (PBO)	Induction - Lebrikizumab (Leb) Q2W
Number of subjects analysed	141	283
Units: Percentage of Participants
number (confidence interval 95%)	12.8 (7.0 to 18.6)	43.0 (37.1 to 49.0)

IGA Baseline to Week 16

Comparison groups

Induction - Placebo (PBO) v Induction - Lebrikizumab (Leb) Q2W

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.000001

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

29.6

Confidence interval

level

95%

sides

2-sided

lower limit

21.4

upper limit

37.8

Primary: Percentage of Participants Achieving Eczema Area And Severity Index (EASI-75) (≥75% Reduction in EASI Score) From Baseline to Week 16

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End point title

Percentage of Participants Achieving Eczema Area And Severity Index (EASI-75) (≥75% Reduction in EASI Score) From Baseline to Week 16

End point description

The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent, i.e., percentage of skin 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 (none) to 72 (severe). The EASI-75 responder is defined as a participant who achieves a ≥ 75% improvement from baseline in the EASI score. APD: All randomized participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. MCMC-MI was used to handle missing data.

End point type

Primary

End point timeframe

Baseline to Week 16

End point values	Induction - Placebo (PBO)	Induction - Lebrikizumab (Leb) Q2W
Number of subjects analysed	141	283
Units: Percentage of Participants
number (confidence interval 95%)	16.4 (9.8 to 23.0)	59.3 (53.4 to 65.2)

EASI-75

Comparison groups

Induction - Placebo (PBO) v Induction - Lebrikizumab (Leb) Q2W

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.000001

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

42.3

Confidence interval

level

95%

sides

2-sided

lower limit

33.5

upper limit

Secondary: Percentage of Participants With an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 2

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End point title

Percentage of Participants With an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 2

End point description

he IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification. APD: All randomized participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. MCMC-MI was used to handle missing data.

End point type

Secondary

End point timeframe

Baseline to Week 2

End point values	Induction - Placebo (PBO)	Induction - Lebrikizumab (Leb) Q2W
Number of subjects analysed	141	283
Units: Percentage of Participants
number (confidence interval 95%)	0.7 (0.0 to 2.1)	2.5 (0.7 to 4.4)

IGA Baseline to Week 2

Comparison groups

Induction - Placebo (PBO) v Induction - Lebrikizumab (Leb) Q2W

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.218644

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

1.7

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6

upper limit

Secondary: Percentage of Participants With an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 4

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End point title

Percentage of Participants With an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 4

End point description

The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification. APD: All randomized participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. MCMC-MI was used to handle missing data.

End point type

Secondary

End point timeframe

Baseline to Week 4

End point values	Induction - Placebo (PBO)	Induction - Lebrikizumab (Leb) Q2W
Number of subjects analysed	141	283
Units: Percentage of Participants
number (confidence interval 95%)	0.8 (-0.7 to 2.3)	10.6 (6.9 to 14.2)

IGA Baseline to Week 4

Comparison groups

Induction - Placebo (PBO) v Induction - Lebrikizumab (Leb) Q2W

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.000982

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

9.6

Confidence interval

level

95%

sides

2-sided

lower limit

5.7

upper limit

13.6

Secondary: Percentage of Participants With an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 16 in Adults

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End point title

Percentage of Participants With an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 16 in Adults

End point description

The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification. APD: All randomized, adult participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. MCMC-MI was used to handle missing data.

End point type

Secondary

End point timeframe

Baseline to Week 16

End point values	Induction - Placebo (PBO)	Induction - Lebrikizumab (Leb) Q2W
Number of subjects analysed	123	246
Units: Percentage of Participants
number (confidence interval 95%)	11.3 (5.4 to 17.2)	42.2 (35.8 to 48.6)

IGA - Adults Baseline to Week 16

Comparison groups

Induction - Placebo (PBO) v Induction - Lebrikizumab (Leb) Q2W

Number of subjects included in analysis

369

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.000001

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

30.8

Confidence interval

level

95%

sides

2-sided

lower limit

22.1

upper limit

39.4

Secondary: Percentage of Participants Achieving EASI-90 (≥90% Reduction in EASI Score) From Baseline to Week 16

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End point title

Percentage of Participants Achieving EASI-90 (≥90% Reduction in EASI Score) From Baseline to Week 16

End point description

The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent i.e., percentage of skin 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 (none) to 72 (severe). The EASI-90responder is defined as a participant who achieves a ≥ 90% improvement from baseline in the EASI score. APD: All randomized participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. MCMC-MI was used to handle missing data.

End point type

Secondary

End point timeframe

Baseline to Week 16

End point values	Induction - Placebo (PBO)	Induction - Lebrikizumab (Leb) Q2W
Number of subjects analysed	141	283
Units: Percentage of Participants
number (confidence interval 95%)	9.0 (3.9 to 14.0)	38.3 (32.5 to 44.1)

EASI-90

Comparison groups

Induction - Placebo (PBO) v Induction - Lebrikizumab (Leb) Q2W

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.000001

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

28.8

Confidence interval

level

95%

sides

2-sided

lower limit

21.3

upper limit

36.3

Secondary: Percent Change in Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16

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End point title

Percent Change in Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16

End point description

Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating “No itch” and 10 indicating “Worst itch imaginable.” Least Squares (LS) Mean was calculated using analysis of covariance (ANCOVA) model with treatment and randomization strata (region, disease severity, age) as fixed factors and baseline value as covariate. APD: All randomized participants, with a Baseline Pruritus NRS score >0, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. MCMC-MI was used to handle missing data.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Induction - Placebo (PBO)	Induction - Lebrikizumab (Leb) Q2W
Number of subjects analysed	136	276
Units: Percent Change
least squares mean (standard error)	-15.06 ± 3.833	-45.48 ± 3.143

Pruritus Numerical Rating Scale (NRS)

Comparison groups

Induction - Placebo (PBO) v Induction - Lebrikizumab (Leb) Q2W

Number of subjects included in analysis

412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.000001

Method

ANCOVA

Parameter type

LS Mean Difference (Final Values)

Point estimate

-30.42

Confidence interval

level

95%

sides

2-sided

lower limit

-38.1

upper limit

-22.7

Variability estimate

Standard error of the mean

Dispersion value

3.915

Secondary: Percentage of Participants With a Pruritus NRS Score of ≥4-points at Baseline Who Achieve a ≥4-point Reduction in Pruritus NRS Score From Baseline to Week 16

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End point title

Percentage of Participants With a Pruritus NRS Score of ≥4-points at Baseline Who Achieve a ≥4-point Reduction in Pruritus NRS Score From Baseline to Week 16

End point description

Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating "No itch" and 10 indicating "Worst itch imaginable." APD: All randomized participants, with a Baseline Pruritus NRS score ≥4, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. MCMC-MI was used to handle missing data.

End point type

Secondary

End point timeframe

Baseline to Week 16

End point values	Induction - Placebo (PBO)	Induction - Lebrikizumab (Leb) Q2W
Number of subjects analysed	130	263
Units: Percentage of Participants
number (confidence interval 95%)	13.0 (7.0 to 18.9)	45.9 (39.8 to 52.1)

Pruritus NRS Score

Comparison groups

Induction - Placebo (PBO) v Induction - Lebrikizumab (Leb) Q2W

Number of subjects included in analysis

393

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.000001

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

32.9

Confidence interval

level

95%

sides

2-sided

lower limit

24.6

upper limit

41.3

Secondary: Percentage of Participants With a Pruritus NRS Score of ≥5-points at Baseline Who Achieve a ≥4-point Reduction in Pruritus NRS Score From Baseline to Week 16

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End point title

Percentage of Participants With a Pruritus NRS Score of ≥5-points at Baseline Who Achieve a ≥4-point Reduction in Pruritus NRS Score From Baseline to Week 16

End point description

Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating "No itch" and 10 indicating "Worst itch imaginable." APD: All randomized participants, with Baseline Pruritus NRS score ≥ 5, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. MCMC-MI was used to handle missing data.

End point type

Secondary

End point timeframe

Baseline to Week 16

End point values	Induction - Placebo (PBO)	Induction - Lebrikizumab (Leb) Q2W
Number of subjects analysed	123	141
Units: Percentage of Participants
number (confidence interval 95%)	13.7 (7.5 to 20.0)	49.0 (42.7 to 55.4)

Pruritus NRS Score

Comparison groups

Induction - Placebo (PBO) v Induction - Lebrikizumab (Leb) Q2W

Number of subjects included in analysis

264

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.000001

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

35.1

Confidence interval

level

95%

sides

2-sided

lower limit

26.3

upper limit

43.9

Secondary: Percent Change in EASI Score From Baseline to Week 16

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End point title

Percent Change in EASI Score From Baseline to Week 16

End point description

The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent, i.e., percentage of skin 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). LS Mean was calculated using ANCOVA model with treatment, stratification factors of geographic region, age group, baseline IGA score (IGA 3 versus 4) as fixed factors baseline value as covariate.

End point type

Secondary

End point timeframe

Baseline, Week 16 APD: All randomized participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. MCMC-MI was used to handle missing data.

End point values	Induction - Placebo (PBO)	Induction - Lebrikizumab (Leb) Q2W
Number of subjects analysed	141	283
Units: Percent Change
least squares mean (standard error)	-26.01 ± 4.031	-64.31 ± 3.156

Percent Change in EASI Score

Comparison groups

Induction - Placebo (PBO) v Induction - Lebrikizumab (Leb) Q2W

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.000001

Method

ANCOVA

Parameter type

LS Mean Difference (Final Values)

Point estimate

-38.31

Confidence interval

level

95%

sides

2-sided

lower limit

-46.4

upper limit

-30.2

Variability estimate

Standard error of the mean

Dispersion value

4.151

Secondary: Change From Baseline in Percent Body Surface Area (BSA) at Week 16

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End point title

Change From Baseline in Percent Body Surface Area (BSA) at Week 16

End point description

The BSA affected by AD will be assessed for 4 separate body regions: head and neck, trunk (including genital region), upper extremities, and lower extremities (including the buttocks). Each body region will be assessed for disease extent ranging from 0% to 100% involvement. BSA was calculated using the participant's palm using the 1% rule, 1 palm was equivalent to 1% with estimates of the number of palms it takes to cover the affected AD area. Maximum number of palms were 10 palms for head and neck (10%), 20 palms for upper extremities (20%), 30 palms for trunk, including axilla and groin (30%), 40 palms for lower extremities, including buttocks (40%). Percent of BSA for a body region was calculated as = total number of palms in a body region * % surface area equivalent to 1 palm. Overall percent BSA of all 4 body regions ranges from 0% to 100 % with higher values representing greater severity of AD. MMRM was used to handle all missing data.

End point type

Secondary

End point timeframe

Baseline, Week 16 APD: All randomized participants, with observed BSA data, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol.

End point values	Induction - Placebo (PBO)	Induction - Lebrikizumab (Leb) Q2W
Number of subjects analysed	77	236
Units: percentage of body surface area
least squares mean (standard error)	-11.77 ± 1.86	-30.2 ± 1.31

BSA

Comparison groups

Induction - Placebo (PBO) v Induction - Lebrikizumab (Leb) Q2W

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.000001

Method

Mixed models analysis

Parameter type

LS Mean Difference (Final Values)

Point estimate

-18.5

Confidence interval

level

95%

sides

2-sided

lower limit

-22.4

upper limit

-14.5

Variability estimate

Standard error of the mean

Dispersion value

Secondary: Percentage of Participants Achieving EASI-90 From Baseline to Week 4

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End point title

Percentage of Participants Achieving EASI-90 From Baseline to Week 4

End point description

The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent, i.e., percentage of skin 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 (none) to 72 (severe). The EASI-90 responder is defined as a participant who achieves a ≥ 90% improvement from baseline in the EASI score. APD: All randomized participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. MCMC-MI was used to handle missing data.

End point type

Secondary

End point timeframe

Baseline to Week 4

End point values	Induction - Placebo (PBO)	Induction - Lebrikizumab (Leb) Q2W
Number of subjects analysed	141	283
Units: Percentage of Participants
number (confidence interval 95%)	1.6 (-0.6 to 3.8)	12.4 (8.5 to 16.3)

EASI-90

Comparison groups

Induction - Placebo (PBO) v Induction - Lebrikizumab (Leb) Q2W

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.000878

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

10.7

Confidence interval

level

95%

sides

2-sided

lower limit

6.2

upper limit

15.2

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

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End point title

Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16

End point description

The DLQI is a 10-item, validated questionnaire used to assess the impact of skin disease on the quality of life of an affected person. The 10 questions cover the following topics: symptoms, embarrassment, shopping and home care, clothes, social and leisure, sport, work or study, close relationships, sex, and treatment, over the previous week. Response categories include "Not at all," "A little," "A lot," and "Very much," with corresponding scores of 0, 1, 2, and 3 respectively. Questions 3-10 also have an additional response category of "Not relevant" which is scored as "0". Questions are scored from 0 to 3, giving a possible total score range from 0 (no impact of skin disease on quality of life) to 30 (maximum impact on quality of life). A high score is indicative of a poor quality of life. LS Mean was calculated using the ANCOVA model with treatment, baseline value, and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors.

End point type

Secondary

End point timeframe

Baseline, Week 16 APD: All randomized participants, with non-missing baseline DLQI score, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol.

End point values	Induction - Placebo (PBO)	Induction - Lebrikizumab (Leb) Q2W
Number of subjects analysed	121 ^[1]	239 ^[2]
Units: Score on a Scale
least squares mean (standard error)	-2.9 ± 1.1	-8.7 ± 1.05

Notes
[1] - MCMC-MI was used to handle missing data.
[2] - MCMC-MI was used to handle missing data.

DLQI

Comparison groups

Induction - Placebo (PBO) v Induction - Lebrikizumab (Leb) Q2W

Number of subjects included in analysis

360

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.000001

Method

ANCOVA

Parameter type

LS Mean Difference (Final Values)

Point estimate

-5.8

Confidence interval

level

95%

sides

2-sided

lower limit

-7.1

upper limit

-4.5

Variability estimate

Standard error of the mean

Dispersion value

0.68

Secondary: Percentage of Participants Achieving ≥4 Point Improvement in DLQI From Baseline to Week 16

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End point title

Percentage of Participants Achieving ≥4 Point Improvement in DLQI From Baseline to Week 16

End point description

he DLQI is a 10-item, validated questionnaire used to assess the impact of skin disease on the quality of life of an affected person. The 10 questions cover the following topics: symptoms, embarrassment, shopping and home care, clothes, social and leisure, sport, work or study, close relationships, sex, and treatment, over the previous week. Response categories include "Not at all," "A little," "A lot," and "Very much," with corresponding scores of 0, 1, 2, and 3 respectively. Questions 3-10 also have an additional response category of "Not relevant" which is scored as "0". Questions are scored from 0 to 3, giving a possible total score range from 0 (no impact of skin disease on quality of life) to 30 (maximum impact on quality of life). A high score is indicative of a poor quality of life. MCMC-MI was used to handle all missing data.

End point type

Secondary

End point timeframe

Baseline to Week 16 APD: All randomized participants, with non-missing baseline DLQI score, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol.

End point values	Induction - Placebo (PBO)	Induction - Lebrikizumab (Leb) Q2W
Number of subjects analysed	121 ^[3]	239 ^[4]
Units: Percentage of Participants
number (confidence interval 95%)	32.4 (23.8 to 41.1)	71.45 (65.7 to 77.4)

Notes
[3] - MCMC-MI was used to handle missing data.
[4] - MCMC-MI was used to handle missing data.

DLQI

Comparison groups

Induction - Placebo (PBO) v Induction - Lebrikizumab (Leb) Q2W

Number of subjects included in analysis

360

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.000001

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

38.8

Confidence interval

level

95%

sides

2-sided

lower limit

28.3

upper limit

49.3

Secondary: Percentage of Participants With a DLQI Total Score of ≥4-point at Baseline Achieving ≥4-point Improvement in DLQI From Baseline to Week 16

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End point title

Percentage of Participants With a DLQI Total Score of ≥4-point at Baseline Achieving ≥4-point Improvement in DLQI From Baseline to Week 16

End point description

End point type

Secondary

End point timeframe

Baseline to Week 16 APD: All randomized participants, with a DLQI Total Score of ≥4-point at baseline, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol.

End point values	Induction - Placebo (PBO)	Induction - Lebrikizumab (Leb) Q2W
Number of subjects analysed	116	226
Units: Percentage of Participants
number (confidence interval 95%)	33.8 (24.9 to 42.8)	75.6 (69.9 to 81.4)

DLQI ≥4-point at Baseline

Comparison groups

Induction - Placebo (PBO) v Induction - Lebrikizumab (Leb) Q2W

Number of subjects included in analysis

342

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.000001

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

41.8

Confidence interval

level

95%

sides

2-sided

lower limit

31.2

upper limit

52.3

Secondary: Percent Change in Sleep-loss Score From Baseline to Week 16

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End point title

Percent Change in Sleep-loss Score From Baseline to Week 16

End point description

Sleep Loss due to interference of itch will be assessed by the participant. Participants rate their interference of itch on sleep based on a 5-point Likert scale [0 (not at all) to 4 (unable to sleep at all)]. Higher scores indicated a greater impact and worse outcome. Assessments will be recorded daily by the participant using an electronic diary. LS Mean was calculated using ANCOVA model with treatment, baseline value, and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors. APD: All randomized participants, with baseline sleep-loss score >0, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. MCMC-MI was used to handle missing data.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Induction - Placebo (PBO)	Induction - Lebrikizumab (Leb) Q2W
Number of subjects analysed	132	269
Units: Percent Change
least squares mean (standard error)	-15.99 ± 5.139	-48.33 ± 4.175

Sleep-loss Score

Comparison groups

Induction - Placebo (PBO) v Induction - Lebrikizumab (Leb) Q2W

Number of subjects included in analysis

401

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.000001

Method

ANCOVA

Parameter type

LS Mean Difference (Final Values)

Point estimate

-32.35

Confidence interval

level

95%

sides

2-sided

lower limit

-42.6

upper limit

-22.1

Variability estimate

Standard error of the mean

Dispersion value

5.23

Secondary: Change From Baseline in Sleep-loss Score at Week 16

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End point title

Change From Baseline in Sleep-loss Score at Week 16

End point description

Sleep Loss due to interference of itch will be assessed by the participant. Participants rate their interference of itch on sleep based on a 5-point Likert scale [0 (not at all) to 4 (unable to sleep at all)]. Higher scores indicated a greater impact and worse outcome. Assessments will be recorded daily by the participant using an electronic diary. LS Mean was calculated using ANCOVA model with treatment, baseline value, and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors. APD: All randomized participants, non-missing baseline Sleep-loss score, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. MCMC-MI was used to handle missing data.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Induction - Placebo (PBO)	Induction - Lebrikizumab (Leb) Q2W
Number of subjects analysed	136	276
Units: Score on a Scale
least squares mean (standard error)	-0.38 ± 0.096	-1.13 ± 0.078

Sleep-loss Score

Comparison groups

Induction - Placebo (PBO) v Induction - Lebrikizumab (Leb) Q2W

Number of subjects included in analysis

412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.000001

Method

ANCOVA

Parameter type

LS Mean Difference (Final Values)

Point estimate

-0.75

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

-0.6

Variability estimate

Standard error of the mean

Dispersion value

0.098

Secondary: Percentage of Participants With a Sleep-loss Score ≥2 Points at Baseline Who Achieve a ≥2 Points Reduction From Baseline at Week 16

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End point title

Percentage of Participants With a Sleep-loss Score ≥2 Points at Baseline Who Achieve a ≥2 Points Reduction From Baseline at Week 16

End point description

Sleep Loss due to interference of itch will be assessed by the participant. Participants rate their interference of itch on sleep based on a 5-point Likert scale [0 (not at all) to 4 (unable to sleep at all)]. Higher scores indicated a greater impact and worse outcome. Assessments will be recorded daily by the participant using an electronic diary. APD: All randomized participants, with baseline sleep-loss score ≥2 Points, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. MCMC-MI was used to handle missing data.

End point type

Secondary

End point timeframe

Baseline to Week 16

End point values	Induction - Placebo (PBO)	Induction - Lebrikizumab (Leb) Q2W
Number of subjects analysed	91	195
Units: Percentage of Participants
number (confidence interval 95%)	4.7 (0.3 to 9.2)	39.0 (32.1 to 46.0)

Sleep-loss Score

Comparison groups

Induction - Placebo (PBO) v Induction - Lebrikizumab (Leb) Q2W

Number of subjects included in analysis

286

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.000001

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

34.6

Confidence interval

level

95%

sides

2-sided

lower limit

26.2

upper limit

Secondary: Percentage of Participants With a Pruritus NRS Score of ≥4 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 1

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End point title

Percentage of Participants With a Pruritus NRS Score of ≥4 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 1

End point description

Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating "No itch" and 10 indicating "Worst itch imaginable." APD: All randomized participants, with a Pruritus NRS Score of ≥4 Points at Baseline, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. MCMC-MI was used to handle missing data.

End point type

Secondary

End point timeframe

Baseline to Week 1

End point values	Induction - Placebo (PBO)	Induction - Lebrikizumab (Leb) Q2W
Number of subjects analysed	130	263
Units: Percentage of Participants
number (confidence interval 95%)	0.8 (0.0 to 2.3)	2.3 (0.5 to 4.1)

Pruritus NRS Score

Comparison groups

Induction - Placebo (PBO) v Induction - Lebrikizumab (Leb) Q2W

Number of subjects included in analysis

393

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.275529

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

1.5

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

3.9

Secondary: Percentage of Participants With a Pruritus NRS Score of ≥4 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 2

Top of page

End point title

Percentage of Participants With a Pruritus NRS Score of ≥4 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 2

End point description

Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating "No itch" and 10 indicating "Worst itch imaginable." APD: All randomized participant, with a Pruritus NRS Score of ≥4 Points at Baseline, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. MCMC-MI was used to handle missing data.

End point type

Secondary

End point timeframe

Baseline to Week 2

End point values	Induction - Placebo (PBO)	Induction - Lebrikizumab (Leb) Q2W
Number of subjects analysed	130	263
Units: Percentage of Participants
number (confidence interval 95%)	0.9 (-0.8 to 2.5)	6.1 (3.2 to 9.0)

Pruritus NRS Score

Comparison groups

Induction - Placebo (PBO) v Induction - Lebrikizumab (Leb) Q2W

Number of subjects included in analysis

393

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.016656

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

5.3

Confidence interval

level

95%

sides

2-sided

lower limit

1.9

upper limit

Secondary: Percentage of Participants With a Pruritus NRS Score of ≥4 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 4

Top of page

End point title

Percentage of Participants With a Pruritus NRS Score of ≥4 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 4

End point description

Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating "No itch" and 10 indicating "Worst itch imaginable." APD: All randomized participants, with a Pruritus NRS Score of ≥4 Points at Baseline, if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. MCMC-MI was used to handle missing data.

End point type

Secondary

End point timeframe

Baseline to Week 4

End point values	Induction - Placebo (PBO)	Induction - Lebrikizumab (Leb) Q2W
Number of subjects analysed	130	263
Units: Percentage of Participants
number (confidence interval 95%)	2.3 (0.0 to 4.9)	21.6 (16.5 to 26.5)

Pruritus NRS Score

Comparison groups

Induction - Placebo (PBO) v Induction - Lebrikizumab (Leb) Q2W

Number of subjects included in analysis

393

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.000003

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

19.3

Confidence interval

level

95%

sides

2-sided

lower limit

13.7

upper limit

Secondary: Percentage of Participants With a Pruritus NRS Score of ≥5 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 1

Top of page

End point title

Percentage of Participants With a Pruritus NRS Score of ≥5 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 1

End point description

Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating "No itch" and 10 indicating "Worst itch imaginable." APD: All randomized participants, with a Pruritus NRS Score of ≥5 Points at Baseline, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. MCMC-MI was used to handle missing data.

End point type

Secondary

End point timeframe

Baseline to Week 1

End point values	Induction - Placebo (PBO)	Induction - Lebrikizumab (Leb) Q2W
Number of subjects analysed	123	244
Units: Percentage of Participants
number (confidence interval 95%)	0.8 (0.0 to 2.4)	2.5 (0.5 to 4.4)

Pruritus NRS Score

Comparison groups

Induction - Placebo (PBO) v Induction - Lebrikizumab (Leb) Q2W

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.244105

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

1.8

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

4.3

Secondary: Percentage of Participants With a Pruritus NRS Score of ≥5 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 2

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End point title

Percentage of Participants With a Pruritus NRS Score of ≥5 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 2

End point description

Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating "No itch" and 10 indicating "Worst itch imaginable." APD: All randomized participants, with a Pruritus NRS Score of ≥5 Points at Baseline, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. MCMC-MI was used to handle missing data.

End point type

Secondary

End point timeframe

Baseline to Week 2

End point values	Induction - Placebo (PBO)	Induction - Lebrikizumab (Leb) Q2W
Number of subjects analysed	123	244
Units: Percentage of Participants
number (confidence interval 95%)	0.9 (-0.9 to 2.7)	6.6 (3.5 to 9.7)

Pruritus NRS Score

Comparison groups

Induction - Placebo (PBO) v Induction - Lebrikizumab (Leb) Q2W

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.01445

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

5.8

Confidence interval

level

95%

sides

2-sided

lower limit

2.2

upper limit

9.4

Secondary: Percentage of Participants With a Pruritus NRS Score of ≥5 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 4

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End point title

Percentage of Participants With a Pruritus NRS Score of ≥5 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 4

End point description

Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating "No itch" and 10 indicating "Worst itch imaginable." APD: All randomized participants, with a Pruritus NRS Score of ≥5 Points at Baseline, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. MCMC-MI was used to handle missing data.

End point type

Secondary

End point timeframe

Baseline to Week 4

End point values	Induction - Placebo (PBO)	Induction - Lebrikizumab (Leb) Q2W
Number of subjects analysed	123	244
Units: Percentage of Participants
number (confidence interval 95%)	2.4 (0.0 to 5.2)	23.1 (17.8 to 28.5)

Pruritus NRS Score

Comparison groups

Induction - Placebo (PBO) v Induction - Lebrikizumab (Leb) Q2W

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.000002

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

20.9

Confidence interval

level

95%

sides

2-sided

lower limit

14.9

upper limit

26.9

Secondary: Percent Change in SCORing Atopic Dermatitis (SCORAD) From Baseline to Week 16

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End point title

Percent Change in SCORing Atopic Dermatitis (SCORAD) From Baseline to Week 16

End point description

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

End point type

Secondary

End point timeframe

Baseline, Week 16 APD: All randomized participants, with baseline SCORAD >0, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol.

End point values	Induction - Placebo (PBO)	Induction - Lebrikizumab (Leb) Q2W
Number of subjects analysed	138	276
Units: Score on a Scale
least squares mean (standard error)	-16.64 ± 3.162	-46.93 ± 2.551

SCORing Atopic Dermatitis

Comparison groups

Induction - Placebo (PBO) v Induction - Lebrikizumab (Leb) Q2W

Number of subjects included in analysis

414

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.000001

Method

ANCOVA

Parameter type

LS Mean Difference (Final Values)

Point estimate

-30.29

Confidence interval

level

95%

sides

2-sided

lower limit

-36.59

upper limit

-24

Variability estimate

Standard error of the mean

Dispersion value

3.203

Secondary: Change From Baseline in European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) at Week 16 - Health State Index

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End point title

Change From Baseline in European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) at Week 16 - Health State Index

End point description

The EQ-5D-5L is a 2-part measurement. The first part is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive the health state index scores using the United Kingdom (UK) algorithm, with scores ranging from -0.594 to 1, and the United States (US) algorithm, with scores ranging from -0.109 to 1, with higher score indicating better health state. LS Mean was calculated using the ANCOVA model with treatment and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate. Missing Values were imputed using last observation carried forward (LOCF) method.

End point type

Secondary

End point timeframe

Baseline, Week 16 APD: All randomized participants, with non-missing EQ-5D-5L data at baseline, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol.

End point values	Induction - Placebo (PBO)	Induction - Lebrikizumab (Leb) Q2W
Number of subjects analysed	141	282
Units: Score on a Scale
least squares mean (standard error)
Health State Index UK	0.0 ± 0.02	0.2 ± 0.01
Health State Index US	0.0 ± 0.01	0.1 ± 0.01

Health State Index UK

Comparison groups

Induction - Placebo (PBO) v Induction - Lebrikizumab (Leb) Q2W

Number of subjects included in analysis

423

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.000001

Method

ANCOVA

Parameter type

LS Mean Difference (Final Values)

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.1

upper limit

0.2

Variability estimate

Standard error of the mean

Dispersion value

0.02

Health State Index US

Comparison groups

Induction - Placebo (PBO) v Induction - Lebrikizumab (Leb) Q2W

Number of subjects included in analysis

423

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.000001

Method

ANCOVA

Parameter type

LS Mean Difference (Final Values)

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.08

upper limit

0.13

Variability estimate

Standard error of the mean

Dispersion value

0.013

Secondary: Change From Baseline in EQ-5D-5L at Week 16 - Visual Analog Scale (VAS)

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End point title

Change From Baseline in EQ-5D-5L at Week 16 - Visual Analog Scale (VAS)

End point description

The EQ-5D-5L is a 2-part measurement. The second part is assessed using a VAS that ranged from 0 to 100 millimeter (mm), where 0 is the worst health you can imagine and 100 is the best health you can imagine. LS Mean was calculated using the ANCOVA model with treatment and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate. APD: All randomized participants, with non-missing EQ-5D-5L data at baseline, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. Missing values were imputed using LOCF method.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Induction - Placebo (PBO)	Induction - Lebrikizumab (Leb) Q2W
Number of subjects analysed	141	282
Units: Score on a Scale
least squares mean (standard error)	2.1 ± 1.64	10.4 ± 1.33

EQ-5D-5L VAS

Comparison groups

Induction - Placebo (PBO) v Induction - Lebrikizumab (Leb) Q2W

Number of subjects included in analysis

423

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.000001

Method

ANCOVA

Parameter type

LS Mean Difference (Final Values)

Point estimate

8.3

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

11.5

Variability estimate

Standard error of the mean

Dispersion value

1.66

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

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End point title

Change From Baseline in Patient Oriented Eczema Measure (POEM) at Week 16

End point description

POEM is a 7-item, validated, questionnaire used by the participant to assess disease symptoms over the last week. The participant is asked to respond to 7 questions on skin dryness, itching, flaking, cracking, sleep loss, bleeding and weeping. All 7 answers carry equal weight with a total possible score from 0 to 28 (answers scored as: No days=0; 1# 2 days = 1; 3-4 days = 2; 5#6 days = 3; everyday = 4). A high score is indicative of a poor quality of life. POEM responses will be captured using an electronic diary and transferred into the clinical database. LS Mean was calculated using MMRM model using treatment, baseline value, visit, the interaction of the baseline value-by-visit, the interaction of treatment by-visit as covariates, geographic region, age group, baseline IGA (3 versus 4) score as fixed. MMRM was used to handle all missing data

End point type

Secondary

End point timeframe

Baseline, Week 16 APD: All randomized participants, with observed POEM data, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol.

End point values	Induction - Placebo (PBO)	Induction - Lebrikizumab (Leb) Q2W
Number of subjects analysed	70	203
Units: Score on a Scale
least squares mean (standard error)	-3.9 ± 0.72	-11.3 ± 0.47

POEM

Comparison groups

Induction - Placebo (PBO) v Induction - Lebrikizumab (Leb) Q2W

Number of subjects included in analysis

273

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.000001

Method

Mixed models analysis

Parameter type

LS Mean Difference (Final Values)

Point estimate

-7.3

Confidence interval

level

95%

sides

2-sided

lower limit

-8.9

upper limit

-5.7

Variability estimate

Standard error of the mean

Dispersion value

0.8

Secondary: Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety at Week 16 - Adolescents

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End point title

Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety at Week 16 - Adolescents

End point description

PROMIS® is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. Participants ≤17 years will complete pediatric versions for the duration of the study. PROMIS anxiety has 8 questions on Emotion Distress-Anxiety (or Pediatric Anxiety Symptom). Each question has 5 response options with values from 1 to 5. Total raw scores were converted to T-Scores (mean = 50 and a standard deviation = 10) with higher scores representing greater anxiety. LS Mean was calculated using the ANCOVA model with treatment and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate. APD: All randomized, adolescent participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. Missing values were imputed using the LOCF method.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Induction - Placebo (PBO)	Induction - Lebrikizumab (Leb) Q2W
Number of subjects analysed	18	37
Units: Score on a Scale
least squares mean (standard error)	-2.80 ± 2.435	-3.87 ± 1.830

PROMIS Anxiety Adolescents

Comparison groups

Induction - Placebo (PBO) v Induction - Lebrikizumab (Leb) Q2W

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.716224

Method

ANCOVA

Parameter type

LS Mean Difference (Final Values)

Point estimate

-1.07

Confidence interval

level

95%

sides

2-sided

lower limit

-6.93

upper limit

4.8

Variability estimate

Standard error of the mean

Dispersion value

2.917

Secondary: Change From Baseline in PROMIS Depression at Week 16 - Adolescent

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End point title

Change From Baseline in PROMIS Depression at Week 16 - Adolescent

End point description

PROMIS® is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. Participants ≤17 years will complete pediatric versions for the duration of the study. PROMIS depression has 8 questions on Emotion Distress-Depression (or Pediatric Depressive Symptom). Each question has 5 response options with values from 1 to 5. Total raw scores were converted to T-Scores (mean = 50 and a standard deviation = 10) with higher scores representing greater depression. LS Mean was calculated using the ANCOVA model with treatment and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate. APD: All randomized, adolescent participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. Missing values were imputed using the LOCF method.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Induction - Placebo (PBO)	Induction - Lebrikizumab (Leb) Q2W
Number of subjects analysed	18	37
Units: Score on a Scale
least squares mean (standard error)	-0.11 ± 2.165	-4.62 ± 1.623

PROMIS Depression Adolescents

Comparison groups

Induction - Placebo (PBO) v Induction - Lebrikizumab (Leb) Q2W

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.089275

Method

ANCOVA

Parameter type

LS Mean Difference (Final Values)

Point estimate

-4.51

Confidence interval

level

95%

sides

2-sided

lower limit

-9.73

upper limit

0.72

Variability estimate

Standard error of the mean

Dispersion value

2.599

Secondary: Change From Baseline in PROMIS Anxiety at Week 16 - Adults

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End point title

Change From Baseline in PROMIS Anxiety at Week 16 - Adults

End point description

PROMIS is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. The PROMIS measures will be completed by the participant in the study clinic. PROMIS anxiety has 8 questions on Emotion Distress-Anxiety (or Pediatric Anxiety Symptom). Each question has 5 response options with values from 1 to 5. Total raw scores were converted to T-Scores (mean = 50 and a standard deviation = 10) with higher scores representing greater anxiety. LS Mean was calculated using the ANCOVA model with treatment and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate. APD: All randomized, adult participants, with Week 16 PROMIS anxiety data, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. Missing values are imputed with the LOCF method.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Induction - Placebo (PBO)	Induction - Lebrikizumab (Leb) Q2W
Number of subjects analysed	122	244
Units: Score on a Scale
least squares mean (standard error)	-0.60 ± 0.660	-3.91 ± 0.475

PROMIS Anxiety Adults

Comparison groups

Induction - Placebo (PBO) v Induction - Lebrikizumab (Leb) Q2W

Number of subjects included in analysis

366

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.000032

Method

ANCOVA

Parameter type

LS Mean Difference (Final Values)

Point estimate

-3.31

Confidence interval

level

95%

sides

2-sided

lower limit

-4.88

upper limit

-1.75

Variability estimate

Standard error of the mean

Dispersion value

0.796

Secondary: Change From Baseline in PROMIS Depression at Week 16 - Adults

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End point title

Change From Baseline in PROMIS Depression at Week 16 - Adults

End point description

PROMIS is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. The PROMIS measures will be completed by the participant in the study clinic. PROMIS depression has 8 questions on Emotion Distress-Depression (or Pediatric Depressive Symptom). Each question has 5 response options with values from 1 to 5. Total raw scores were converted to T-Scores (mean = 50 and a standard deviation = 10) with higher scores representing greater depression. LS Mean was calculated using the ANCOVA model with treatment and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate. APD: All randomized , adult participants, with Week 16 PROMIS Depression data, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. Missing values were imputed using the LOCF method.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Induction - Placebo (PBO)	Induction - Lebrikizumab (Leb) Q2W
Number of subjects analysed	122	244
Units: Score on a Scale
least squares mean (standard error)	-0.37 ± 0.579	-3.07 ± 0.416

PROMIS Depression Adults

Comparison groups

Induction - Placebo (PBO) v Induction - Lebrikizumab (Leb) Q2W

Number of subjects included in analysis

366

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.000127

Method

ANCOVA

Parameter type

LS Mean Difference (Final Values)

Point estimate

-2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-4.07

upper limit

-1.33

Variability estimate

Standard error of the mean

Dispersion value

0.697

Secondary: Change From Baseline in Asthma Control Questionnaire (ACQ-5) Score at Week 16 in Participants Who Have Self-Reported Comorbid Asthma

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End point title

Change From Baseline in Asthma Control Questionnaire (ACQ-5) Score at Week 16 in Participants Who Have Self-Reported Comorbid Asthma

End point description

The ACQ-5 is a five-item, self-completed questionnaire, which is used as a measure of asthma control of a participant. The five questions (concerning nocturnal awakening, waking in the morning, activity limitation, shortness of breath and wheeze) enquire about the frequency and/or severity of symptoms over the previous week. The response options for all these questions range from zero (no impairment/limitation) to six (total impairment/ limitation) scale. The ACQ-5 score is the average of the individual item scores and ranges from 0 (totally controlled) to 6 (severely uncontrolled). Higher scores indicate lower asthma control. LS Mean was calculated using ANCOVA with treatment, geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate. APD: All randomized participants, with non-missing baseline ACQ-5 score, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not f

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Induction - Placebo (PBO)	Induction - Lebrikizumab (Leb) Q2W
Number of subjects analysed	51	95
Units: Score on a Scale
least squares mean (standard error)	-0.05 ± 0.117	-0.14 ± 0.095

Asthma Control Questionnaire

Comparison groups

Induction - Placebo (PBO) v Induction - Lebrikizumab (Leb) Q2W

Number of subjects included in analysis

146

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.455291

Method

ANCOVA

Parameter type

LS Mean Difference (Final Values)

Point estimate

-0.09

Confidence interval

level

95%

sides

2-sided

lower limit

-0.33

upper limit

0.15

Variability estimate

Standard error of the mean

Dispersion value

0.121

Secondary: Change From Baseline in Children’s Dermatology Life Quality Index (CDLQI) at Week 16 - Adolescents

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End point title

Change From Baseline in Children’s Dermatology Life Quality Index (CDLQI) at Week 16 - Adolescents

End point description

The CDLQI questionnaire is designed for use in children (4 to 16 years of age). It consists of 10 items that are grouped into 6 domains: symptoms & feelings, leisure, school or holidays, personal relationships, sleep, & treatment. The scoring of each question is: Very much =3; Quite a lot = 2; Only a little = 1; Not at all = 0. CDLQI total score is calculated by summing all 10 items responses, and has a range of 0 to 30 (higher scores are indicative of greater impairment). LS Mean was calculated using MMRM model which includes treatment, baseline value, visit, the interaction of the baseline value-by-visit as covariates, the interaction of treatment by-visit, geographic region, age group, and baseline IGA (3 versus 4) score as fixed factors. MMRM was used to handle all missing data.

End point type

Secondary

End point timeframe

Baseline, Week 16 APD: All randomized, adolescent participants, with non-missing baseline CDLQI score, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol.

End point values	Induction - Placebo (PBO)	Induction - Lebrikizumab (Leb) Q2W
Number of subjects analysed	9	26
Units: Score on a Scale
least squares mean (standard error)	-1.0 ± 1.29	-8.0 ± 0.80

Children’s Dermatology Life Quality Index

Comparison groups

Induction - Placebo (PBO) v Induction - Lebrikizumab (Leb) Q2W

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.000069

Method

Mixed models analysis

Parameter type

LS Mean Difference (Final Values)

Point estimate

-7

Confidence interval

level

95%

sides

2-sided

lower limit

-10.1

upper limit

-3.9

Variability estimate

Standard error of the mean

Dispersion value

1.52

Secondary: Pharmacokinetics (PK): Average Serum Concentration of Lebrikizumab at Week 52

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End point title

Pharmacokinetics (PK): Average Serum Concentration of Lebrikizumab at Week 52

End point description

PK: Average serum concentration of lebrikizumab at the Week 52 trough timepoint. Serum concentration is a combined measure obtained from Baseline, Week 4, Week 16, Week 32, Week 52 and average measure was reported at week 52. APD: All participants who were randomly assigned to lebrikizumab 250 mg Q2W at Baseline visit and randomly reassigned to lebrikizumab 250 mg Q2W, lebrikizumab 250 mg Q4W, or placebo at Week 16 and had evaluable PK data at Week 52. The 250 mg Q2W PK population also includes any placebo participants entering the Escape Arm at W16 and participants in the Maintenance Period entering the Escape Arm from 250 mg Q2W dosing.

End point type

Secondary

End point timeframe

Predose: Baseline, Week 4, Week 16, Week 32, Week 52

End point values	Maintenance - Lebrikizumab Responder/Lebrikizumab 250 Q4W
Number of subjects analysed	51
Units: micrograms per milliliter (ug/mL)
arithmetic mean (standard deviation)	40.7 ± 23.7

No statistical analyses for this end point

Secondary: Percentage of Participants From Those Re-randomized Having Achieved EASI-75 at Week 16 Who Continued to Exhibit EASI-75 at Week 52 (EASI-75 Calculated Relative to Baseline EASI Score)

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End point title

Percentage of Participants From Those Re-randomized Having Achieved EASI-75 at Week 16 Who Continued to Exhibit EASI-75 at Week 52 (EASI-75 Calculated Relative to Baseline EASI Score)

End point description

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-75 score was obtained by weight-averaging these 4 scores and will range from 0 (none) to 72 (severe). The EASI-75 responder is defined as a participant who achieves a ≥ 75% improvement from baseline in the EASI score. Analysis Population Description (APD): All participants who were randomly assigned to lebrikizumab 250 mg Q2W at Baseline visit and randomly reassigned to lebrikizumab 250 mg Q2W, lebrikizumab 250 mg Q4W, or placebo at Week 16 and received at least 1 dose of the study treatment during the Maintenance Period.

End point type

Secondary

End point timeframe

Baseline to Week 52

End point values	Maintenance - Lebrikizumab Responder/Placebo	Maintenance - Lebrikizumab Responder/Lebrikizumab 250 Q4W	Maintenance - Lebrikizumab Responder/Lebrikizumab 250 Q2W
Number of subjects analysed	30	62	61
Units: percentage of participants
number (confidence interval 95%)	61.3 (42.3 to 80.4)	79.2 (68.0 to 90.4)	79.2 (67.6 to 90.8)

EASI-75 at Week 52

Comparison groups

Maintenance - Lebrikizumab Responder/Placebo v Maintenance - Lebrikizumab Responder/Lebrikizumab 250 Q4W

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.072375

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

17.9

Confidence interval

level

95%

sides

2-sided

lower limit

-2.3

upper limit

38.1

EASI-75 at Week 52

Comparison groups

Maintenance - Lebrikizumab Responder/Placebo v Maintenance - Lebrikizumab Responder/Lebrikizumab 250 Q2W

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.106653

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

17.5

Confidence interval

level

95%

sides

2-sided

lower limit

-4.5

upper limit

39.5

Secondary: Percentage of Participants From Those Re-randomized Having Achieved IGA 0 or 1 and a ≥2-point Improvement From Baseline at Week 16 Who Continue to Exhibit and IGA 0 or 1 and a ≥2-point Improvement From Baseline at Week 52

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End point title

Percentage of Participants From Those Re-randomized Having Achieved IGA 0 or 1 and a ≥2-point Improvement From Baseline at Week 16 Who Continue to Exhibit and IGA 0 or 1 and a ≥2-point Improvement From Baseline at Week 52

End point description

The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification. APD: All participants who were randomized to Lebrikizumab 250 mg Q2W at Baseline Visit and re-randomized to Lebrikizumab 250 mg Q2W, Lebrikizumab 250 mg Q4W or placebo at Week 16 and received at least 1 dose of study treatment during the maintenance period.

End point type

Secondary

End point timeframe

Baseline to Week 52

End point values	Maintenance - Lebrikizumab Responder/Placebo	Maintenance - Lebrikizumab Responder/Lebrikizumab 250 Q4W	Maintenance - Lebrikizumab Responder/Lebrikizumab 250 Q2W
Number of subjects analysed	30	63	62
Units: percentage of participants
number (confidence interval 95%)	46.5 (24.4 to 68.7)	74.2 (60.5 to 88.0)	75.8 (62.9 to 88.7)

IGA 0 or 1 and a ≥2-point Improvement

Comparison groups

Maintenance - Lebrikizumab Responder/Lebrikizumab 250 Q4W v Maintenance - Lebrikizumab Responder/Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.029857

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

2.8

upper limit

53.2

IGA 0 or 1 and a ≥2-point Improvement

Comparison groups

Maintenance - Lebrikizumab Responder/Placebo v Maintenance - Lebrikizumab Responder/Lebrikizumab 250 Q2W

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.019744

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

4.6

upper limit

53.3

Secondary: Percentage of Participants From Those With a Pruritus NRS of ≥4-points at Baseline Re-randomized Having Achieved ≥4-point Reduction From Baseline at Week 16 Who Continue to Exhibit ≥4-point Reduction From Baseline at Week 52

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End point title

Percentage of Participants From Those With a Pruritus NRS of ≥4-points at Baseline Re-randomized Having Achieved ≥4-point Reduction From Baseline at Week 16 Who Continue to Exhibit ≥4-point Reduction From Baseline at Week 52

End point description

Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating "No itch" and 10 indicating "Worst itch imaginable." APD: All participants who were randomized to Lebrikizumab 250 mg Q2W at Baseline Visit and re-randomized to Lebrikizumab 250 mg Q2W, Lebrikizumab 250 mg Q4W or placebo at Week 16 and received at least 1 dose of study treatment during the maintenance period.

End point type

Secondary

End point timeframe

Baseline to Week 52

End point values	Maintenance - Lebrikizumab Responder/Placebo	Maintenance - Lebrikizumab Responder/Lebrikizumab 250 Q4W	Maintenance - Lebrikizumab Responder/Lebrikizumab 250 Q2W
Number of subjects analysed	17	29	38
Units: percentage of participants
number (confidence interval 95%)	65.4 (41.5 to 89.3)	80.4 (63.5 to 97.3)	81.2 (68.0 to 94.3)

NRS ≥4-point Reduction From Baseline at Week 52

Comparison groups

Maintenance - Lebrikizumab Responder/Placebo v Maintenance - Lebrikizumab Responder/Lebrikizumab 250 Q4W

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.268265

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

15.8

Confidence interval

level

95%

sides

2-sided

lower limit

-12.2

upper limit

43.8

NRS ≥4-point Reduction From Baseline at Week 52

Comparison groups

Maintenance - Lebrikizumab Responder/Placebo v Maintenance - Lebrikizumab Responder/Lebrikizumab 250 Q2W

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.192776

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

16.6

Confidence interval

level

90%

sides

2-sided

lower limit

-9.4

upper limit

42.7

Secondary: Percentage of Participants From Those With a Pruritus NRS of ≥5-points at Baseline Re-randomized Having Achieved ≥4-point Reduction From Baseline at Week 16 Who Continue to Exhibit ≥4-point Reduction From Baseline at Week 52

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End point title

Percentage of Participants From Those With a Pruritus NRS of ≥5-points at Baseline Re-randomized Having Achieved ≥4-point Reduction From Baseline at Week 16 Who Continue to Exhibit ≥4-point Reduction From Baseline at Week 52

End point description

Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating "No itch" and 10 indicating "Worst itch imaginable." APD: All participants who were randomized to Lebrikizumab 250 mg Q2W at Baseline Visit and re-randomized to Lebrikizumab 250 mg Q2W, Lebrikizumab 250 mg Q4W or placebo at Week 16 and received at least 1 dose of study treatment during the maintenance period.

End point type

Secondary

End point timeframe

Baseline to Week 52

End point values	Maintenance - Lebrikizumab Responder/Placebo	Maintenance - Lebrikizumab Responder/Lebrikizumab 250 Q4W	Maintenance - Lebrikizumab Responder/Lebrikizumab 250 Q2W
Number of subjects analysed	17	28	38
Units: percentage of participants
number (confidence interval 95%)	65.4 (41.5 to 89.3)	83.3 (66.7 to 99.9)	81.2 (68.0 to 94.3)

NRS ≥4-point Reduction From Baseline at Week 52

Comparison groups

Maintenance - Lebrikizumab Responder/Placebo v Maintenance - Lebrikizumab Responder/Lebrikizumab 250 Q4W

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.185361

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

18.6

Confidence interval

level

95%

sides

2-sided

lower limit

-9.3

upper limit

46.6

NRS ≥4-point Reduction From Baseline at Week 52

Comparison groups

Maintenance - Lebrikizumab Responder/Placebo v Maintenance - Lebrikizumab Responder/Lebrikizumab 250 Q2W

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.192776

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

16.6

Confidence interval

level

95%

sides

2-sided

lower limit

-9.4

upper limit

42.7

Secondary: Percent Change in SCORAD (Having Achieved EASI-75 at Week 16) From Baseline at Week 52

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End point title

Percent Change in SCORAD (Having Achieved EASI-75 at Week 16) From Baseline at Week 52

End point description

The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3) oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with VAS where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), & subjective symptoms (C: 0-20) combine using A/5 + 7*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. APD: All participants who were randomized to Lebrikizumab 250 mg Q2W at Baseline Visit and re-randomized to Lebrikizumab 250 mg Q2W, Lebrikizumab 250 mg Q4W or placebo at Week 16 and received at least 1 dose of study treatment during the maintenance period.

End point type

Secondary

End point timeframe

Baseline, Week 52

End point values	Maintenance - Lebrikizumab Responder/Placebo	Maintenance - Lebrikizumab Responder/Lebrikizumab 250 Q4W	Maintenance - Lebrikizumab Responder/Lebrikizumab 250 Q2W
Number of subjects analysed	29 ^[5]	59 ^[6]	60 ^[7]
Units: Percent Change
least squares mean (standard error)	-69.65 ± 3.972	-71.39 ± 2.870	-75.28 ± 2.818

Notes
[5] - Missing Values were imputed using LOCF method.
[6] - Missing Values were imputed using LOCF method.
[7] - Missing Values were imputed using LOCF method.

Percent Change in SCORAD

Comparison groups

Maintenance - Lebrikizumab Responder/Placebo v Maintenance - Lebrikizumab Responder/Lebrikizumab 250 Q2W

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.714208

Method

ANCOVA

Parameter type

LS Mean Difference (Final Values)

Point estimate

-1.75

Confidence interval

level

95%

sides

2-sided

lower limit

-11.75

upper limit

7.66

Variability estimate

Standard error of the mean

Dispersion value

4.756

Percent Change in SCORAD

Comparison groups

Maintenance - Lebrikizumab Responder/Placebo v Maintenance - Lebrikizumab Responder/Lebrikizumab 250 Q2W

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.237855

Method

ANCOVA

Parameter type

LS Mean Difference (Final Values)

Point estimate

-5.63

Confidence interval

level

95%

sides

2-sided

lower limit

-15.01

upper limit

3.76

Variability estimate

Standard error of the mean

Dispersion value

4.748

Adverse events

Top of page

Timeframe for reporting adverse events

Baseline up to Week 52

Adverse event reporting additional description

All randomized participants who received at least one dose of study drug. 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

24.1

Reporting group title

Induction Period - Lebrikizumab Q2W

Reporting group description

Reporting group title

Induction Period - Placebo

Reporting group description

Induction Period (Baseline-Week 16): Two subcutaneous (SC) injections of Placebo as a loading dose at Baseline and Week 2 followed by a single injection every 2 weeks (Q2W) from Week 4 until Week 14.

Reporting group title

Maintenance - Lebrikizumab Responder/Placebo

Reporting group description

Maintenance Blinded Period (Week 16 to Week 52): One SC injection of Placebo Q2W.

Reporting group title

Maintenance - Lebrikizumab Responder/Lebrikizumab 250 Q2W

Reporting group description

Maintenance Blinded Period (Week 16 to Week 52): One 250 mg Lebrikizumab SC injection Q2W.

Reporting group title

Maintenance - Lebrikizumab Responder/Lebrikizumab 250 Q4W

Reporting group description

Maintenance Blinded Period (Week 16-Week 52): One 250 mg Lebrikizumab SC injection and one placebo SC injection as maintenance loading dose on Week 16 and two placebo SC injections on Week 18. One 250 mg Lebrikizumab SC injection Every 4 weeks (Q4W) on Weeks 20, 24, 28, 32, 36, 40, 44, and 48. One placebo SC injection Q4W on Weeks 22, 26, 30, 34, 38, 42, 46, and 50.

Reporting group title

Maintenance - Placebo Responder/ Placebo

Reporting group description

Maintenance Blinded Period (Week 16 to Week 52): One SC injection of Placebo Q2W.

Reporting group title

Maintenance - Placebo Responder/ Lebrikizumab 250 Q4W

Reporting group description

Maintenance Blinded Period (Week 16 to Week 52): One 250 mg Lebrikizumab SC injection and one placebo SC injection as maintenance loading dose on Week 16 and two placebo SC injections on Week 18. One 250 mg Lebrikizumab SC injection Every 4 weeks (Q4W) on Weeks 20, 24, 28, 32, 36, 40, 44, and 48. One placebo SC injection Q4W on Weeks 22, 26, 30, 34, 38, 42, 46, and 50.

Reporting group title

Maintenance - Placebo Responder/Lebrikizumab 250 Q2W

Reporting group description

Maintenance Blinded Period (Week 16 to Week 52): One 250 mg Lebrikizumab SC injection Q2W.

Reporting group title

Escape Arm Week 16 - Maintenance OL - PBO NR/Leb 250 Q2W

Reporting group description

Maintenance Escape Period (Week 16 to Week 52): One 250 mg Lebrikizumab SC injection Q2W.

Reporting group title

Escape Arm Week 16 - Maintenance OL - Leb NR/Leb 250 Q2W

Reporting group description

Maintenance Escape Period (Week 16 to Week 52): One 250 mg Lebrikizumab SC injection Q2W.

Reporting group title

Escape Arm Week 24 to 48 - Maintenance OL - Leb 250 Q2W

Reporting group description

Maintenance Escape Period (Week 24 to Week 48): One 250 mg Lebrikizumab SC injection Q2W.

Serious adverse events	Induction Period - Lebrikizumab Q2W	Induction Period - Placebo	Maintenance - Lebrikizumab Responder/Placebo	Maintenance - Lebrikizumab Responder/Lebrikizumab 250 Q2W	Maintenance - Lebrikizumab Responder/Lebrikizumab 250 Q4W	Maintenance - Placebo Responder/ Placebo	Maintenance - Placebo Responder/ Lebrikizumab 250 Q4W	Maintenance - Placebo Responder/Lebrikizumab 250 Q2W	Escape Arm Week 16 - Maintenance OL - PBO NR/Leb 250 Q2W	Escape Arm Week 16 - Maintenance OL - Leb NR/Leb 250 Q2W	Escape Arm Week 24 to 48 - Maintenance OL - Leb 250 Q2W
Total subjects affected by serious adverse events
subjects affected / exposed	6 / 282 (2.13%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	2 / 63 (3.17%)	1 / 4 (25.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	4 / 106 (3.77%)	0 / 18 (0.00%)
number of deaths (all causes)	0	0	0	0	0	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0	0	0	0	0
Injury, poisoning and procedural complications
accidental overdose
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
thermal burn
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
myocardial infarction
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
carpal tunnel syndrome
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
oedema peripheral
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
dysmenorrhoea
alternative dictionary used: MedDRA 24.1
subjects affected / exposed ^[1]	0 / 141 (0.00%)	0 / 73 (0.00%)	0 / 21 (0.00%)	0 / 28 (0.00%)	0 / 38 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 45 (0.00%)	1 / 43 (2.33%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
micromastia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
cholecystitis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
somatic symptom disorder
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
arthralgia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
arthritis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
synovitis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
covid-19
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
cellulitis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
pneumonia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	1 / 4 (25.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
sepsis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	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.

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Induction Period - Lebrikizumab Q2W	Induction Period - Placebo	Maintenance - Lebrikizumab Responder/Placebo	Maintenance - Lebrikizumab Responder/Lebrikizumab 250 Q2W	Maintenance - Lebrikizumab Responder/Lebrikizumab 250 Q4W	Maintenance - Placebo Responder/ Placebo	Maintenance - Placebo Responder/ Lebrikizumab 250 Q4W	Maintenance - Placebo Responder/Lebrikizumab 250 Q2W	Escape Arm Week 16 - Maintenance OL - PBO NR/Leb 250 Q2W	Escape Arm Week 16 - Maintenance OL - Leb NR/Leb 250 Q2W	Escape Arm Week 24 to 48 - Maintenance OL - Leb 250 Q2W
Total subjects affected by non serious adverse events
subjects affected / exposed	127 / 282 (45.04%)	73 / 141 (51.77%)	15 / 32 (46.88%)	25 / 62 (40.32%)	32 / 63 (50.79%)	2 / 4 (50.00%)	4 / 10 (40.00%)	3 / 10 (30.00%)	51 / 96 (53.13%)	47 / 106 (44.34%)	8 / 18 (44.44%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
cutaneous t-cell lymphoma
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
haemangioma
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
histiocytic necrotising lymphadenitis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
penile squamous cell carcinoma
alternative dictionary used: MedDRA 24.1
subjects affected / exposed ^[2]	0 / 141 (0.00%)	0 / 68 (0.00%)	0 / 11 (0.00%)	0 / 34 (0.00%)	0 / 25 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 51 (0.00%)	1 / 63 (1.59%)	0 / 13 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
skin papilloma
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	1 / 18 (5.56%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	1
Vascular disorders
hypertension
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	3 / 282 (1.06%)	1 / 141 (0.71%)	0 / 32 (0.00%)	2 / 62 (3.23%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	3	1	0	3	0	0	0	0	0	0	0
peripheral venous disease
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
General disorders and administration site conditions
administration site reaction
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
asthenia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	0	0	0
chest discomfort
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
chills
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0	0	0
fatigue
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	2 / 282 (0.71%)	1 / 141 (0.71%)	1 / 32 (3.13%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	2	1	1	0	0	0	0	0	1	0	0
hyperthermia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
injection site bruising
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0	0	0
injection site erythema
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	2 / 282 (0.71%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	0	0	0
injection site pain
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	2 / 141 (1.42%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	2	6	0	0	0	0	0	0	1	0	0
injection site pruritus
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
injection site reaction
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	2 / 96 (2.08%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	3	1	0
injection site swelling
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	1 / 18 (5.56%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	6
non-cardiac chest pain
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
oedema
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
oedema peripheral
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	3 / 282 (1.06%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	4	0	0	0	0	0	0	0	0	0	0
pyrexia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	1 / 32 (3.13%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0	0	1	0
swelling face
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
vaccination site pain
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	2 / 96 (2.08%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	0	0
Immune system disorders
food allergy
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	1	0	0	0	0	0	0
hypersensitivity
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
seasonal allergy
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
Reproductive system and breast disorders
benign prostatic hyperplasia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed ^[3]	0 / 141 (0.00%)	0 / 68 (0.00%)	0 / 11 (0.00%)	0 / 34 (0.00%)	1 / 25 (4.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 51 (1.96%)	0 / 63 (0.00%)	0 / 13 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	1	0	0
cervical dysplasia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed ^[4]	0 / 141 (0.00%)	0 / 73 (0.00%)	0 / 21 (0.00%)	0 / 28 (0.00%)	0 / 38 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 45 (2.22%)	0 / 43 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
dysmenorrhoea
alternative dictionary used: MedDRA 24.1
subjects affected / exposed ^[5]	3 / 141 (2.13%)	0 / 73 (0.00%)	0 / 21 (0.00%)	0 / 28 (0.00%)	0 / 38 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 45 (0.00%)	1 / 43 (2.33%)	0 / 5 (0.00%)
occurrences all number	5	0	0	0	0	0	0	0	0	4	0
galactorrhoea
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
heavy menstrual bleeding
alternative dictionary used: MedDRA 24.1
subjects affected / exposed ^[6]	1 / 141 (0.71%)	0 / 73 (0.00%)	0 / 21 (0.00%)	0 / 28 (0.00%)	0 / 38 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 45 (0.00%)	0 / 43 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
vaginal haemorrhage
alternative dictionary used: MedDRA 24.1
subjects affected / exposed ^[7]	0 / 141 (0.00%)	0 / 73 (0.00%)	0 / 21 (0.00%)	0 / 28 (0.00%)	0 / 38 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 45 (0.00%)	1 / 43 (2.33%)	0 / 5 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Respiratory, thoracic and mediastinal disorders
asthma
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	3 / 282 (1.06%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	4 / 106 (3.77%)	0 / 18 (0.00%)
occurrences all number	3	1	0	0	0	0	0	0	1	4	0
chronic obstructive pulmonary disease
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
cough
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	1	0	0	1	0	0	0	1	0	0
dyspnoea
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	1	0
epistaxis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
nasal congestion
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
nasal inflammation
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
oropharyngeal pain
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
paranasal sinus inflammation
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
reflux laryngitis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
rhinitis allergic
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	2 / 282 (0.71%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	3 / 106 (2.83%)	0 / 18 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	1	3	0
rhinorrhoea
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	0	0	0	1	0	0	0
sinus congestion
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
sleep apnoea syndrome
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Psychiatric disorders
anxiety
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	4 / 282 (1.42%)	0 / 141 (0.00%)	0 / 32 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	6	0	0	1	0	0	0	0	0	0	0
attention deficit hyperactivity disorder
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
delirium
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
depression
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	2 / 282 (0.71%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	3 / 106 (2.83%)	0 / 18 (0.00%)
occurrences all number	2	1	0	0	0	0	0	0	0	3	0
insomnia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	1 / 141 (0.71%)	0 / 32 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	1	0	1	0	0	0	0	0	0	0
persistent depressive disorder
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
sleep disorder
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
stress
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Investigations
alanine aminotransferase increased
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
aspartate aminotransferase increased
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	1 / 62 (1.61%)	2 / 63 (3.17%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	1	2	0	0	0	0	0	0
blood creatinine increased
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
blood lactate dehydrogenase increased
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	1	0	0	0	0	0	0
blood phosphorus decreased
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
blood potassium increased
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
blood pressure increased
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
blood urea increased
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
blood uric acid increased
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
eosinophil count increased
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	1	0
haemoglobin urine present
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
hepatic enzyme increased
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	1	0	0
lymphocyte count decreased
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	1	0	0
lymphocyte morphology abnormal
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	1 / 32 (3.13%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0
neutrophil count decreased
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
neutrophil count increased
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
nitrite urine present
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
platelet count increased
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
protein urine present
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
smear cervix abnormal
alternative dictionary used: MedDRA 24.1
subjects affected / exposed ^[8]	0 / 141 (0.00%)	0 / 73 (0.00%)	0 / 21 (0.00%)	0 / 28 (0.00%)	0 / 38 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 45 (2.22%)	0 / 43 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
strongyloides test positive
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
transaminases increased
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
urine bilirubin increased
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
urine leukocyte esterase positive
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
weight increased
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	1 / 62 (1.61%)	1 / 63 (1.59%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	0	0	0
Injury, poisoning and procedural complications
arthropod bite
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	1 / 32 (3.13%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0
back injury
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
burns second degree
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
contusion
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	2 / 63 (3.17%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	2	0	0	0	1	1	0
epicondylitis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
head injury
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
ligament sprain
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	1	0	0	0	1	0	0
meniscus injury
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
muscle strain
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	1	0	0
overdose
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	1	0	0	0	0	0	0
pelvic fracture
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
post procedural inflammation
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
procedural pain
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
radius fracture
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
sunburn
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	1	0	1	0	0	0	0
thermal burn
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
tooth fracture
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
tooth injury
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
upper limb fracture
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
vaccination complication
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	3 / 96 (3.13%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	1	0	0	2	3	1	0
Cardiac disorders
angina pectoris
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
palpitations
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
tachycardia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
Nervous system disorders
carpal tunnel syndrome
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	1 / 18 (5.56%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1
dizziness
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	2 / 282 (0.71%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	5	1	0	0	0	0	0	0	0	0	0
dysgeusia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
epilepsy
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
essential tremor
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
headache
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	9 / 282 (3.19%)	2 / 141 (1.42%)	0 / 32 (0.00%)	0 / 62 (0.00%)	2 / 63 (3.17%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	4 / 106 (3.77%)	0 / 18 (0.00%)
occurrences all number	10	2	0	0	2	0	0	0	0	7	0
hypersomnia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
migraine
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
post herpetic neuralgia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
presyncope
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
radiculopathy
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
sciatica
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	1	0	0
seizure
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
syncope
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Blood and lymphatic system disorders
anaemia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
eosinophilia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	2 / 141 (1.42%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	3 / 106 (2.83%)	0 / 18 (0.00%)
occurrences all number	1	2	0	0	0	0	0	0	0	3	0
erythropenia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	1	0	0	0	0	0	0	0
immune thrombocytopenia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	2 / 96 (2.08%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	0	0
iron deficiency anaemia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	1	0	0	0	0	0	0	0
leukopenia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	1 / 4 (25.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
lymphadenopathy
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	1 / 4 (25.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	2 / 96 (2.08%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	3	0	0
lymphopenia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	1	1	0
neutropenia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
splenomegaly
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	1 / 4 (25.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
thrombocytopenia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	2 / 282 (0.71%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	1	1	0
Ear and labyrinth disorders
deafness unilateral
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
vertigo
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Eye disorders
angle closure glaucoma
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
blepharitis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	3 / 282 (1.06%)	0 / 141 (0.00%)	0 / 32 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	3	0	0	1	0	0	0	0	1	1	0
cataract
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
chalazion
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	2 / 282 (0.71%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	0	0	0
conjunctival disorder
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
conjunctival hyperaemia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
conjunctivitis allergic
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	7 / 282 (2.48%)	1 / 141 (0.71%)	1 / 32 (3.13%)	1 / 62 (1.61%)	3 / 63 (4.76%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	6 / 96 (6.25%)	5 / 106 (4.72%)	1 / 18 (5.56%)
occurrences all number	7	1	1	1	3	0	0	0	7	5	1
dry eye
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	2 / 141 (1.42%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	2 / 106 (1.89%)	0 / 18 (0.00%)
occurrences all number	1	2	0	0	0	0	0	0	0	2	0
eye irritation
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	2 / 282 (0.71%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	1 / 18 (5.56%)
occurrences all number	2	0	0	0	0	0	0	0	0	0	1
eye pain
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
eye pruritus
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	2 / 96 (2.08%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	4	0	0
eyelid irritation
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
eyelid oedema
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	3	0	0	0	0	0	0
eyelids pruritus
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
glaucomatocyclitic crises
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
keratitis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
keratoconus
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
lacrimation increased
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
meibomian gland dysfunction
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
ocular hyperaemia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	2 / 106 (1.89%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0
pupils unequal
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
vernal keratoconjunctivitis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	1	0	0	0	0	0	0	0
vision blurred
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
visual impairment
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Gastrointestinal disorders
abdominal discomfort
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
abdominal pain
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	1	0	0	0	0	1	0	0
anal haemorrhage
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
constipation
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
dental caries
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
diarrhoea
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	1 / 32 (3.13%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	1	0	0
gastric polyps
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
gastrointestinal inflammation
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	1	0	0	0	0	0	0	0
mouth ulceration
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
nausea
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	2 / 141 (1.42%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0	0	0
odynophagia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
toothache
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	1 / 18 (5.56%)
occurrences all number	1	1	0	0	0	0	0	0	0	0	1
vomiting
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0	0	1	0
Hepatobiliary disorders
cholelithiasis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	1 / 32 (3.13%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0
hepatic steatosis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
non-alcoholic steatohepatitis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Skin and subcutaneous tissue disorders
acne
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	2 / 106 (1.89%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0
alopecia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
alopecia areata
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
dermal cyst
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	2 / 96 (2.08%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	2	0	0
dermatitis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
dermatitis atopic
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	16 / 282 (5.67%)	30 / 141 (21.28%)	4 / 32 (12.50%)	2 / 62 (3.23%)	4 / 63 (6.35%)	2 / 4 (50.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	6 / 96 (6.25%)	4 / 106 (3.77%)	1 / 18 (5.56%)
occurrences all number	17	33	4	2	4	2	0	0	6	5	1
dermatitis contact
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
drug eruption
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
dyshidrotic eczema
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
eczema
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
erythema
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	1 / 62 (1.61%)	1 / 63 (1.59%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	1	0	0
ingrowing nail
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	1	0
milia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
miliaria
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	0	0
papule
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
photosensitivity reaction
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
pruritus
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	3 / 282 (1.06%)	6 / 141 (4.26%)	0 / 32 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	3	7	0	0	1	0	0	0	0	1	0
rash
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	2	0	0	0	0	0	0
seborrhoea
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
seborrhoeic dermatitis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	2 / 282 (0.71%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	2	1	0	0	0	0	0	0	0	0	0
skin burning sensation
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
skin lesion inflammation
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
solar dermatitis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
solar lentigo
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	1	0	0
urticaria
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	1	0	0	0	0	0	0
Renal and urinary disorders
cystitis noninfective
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
haematuria
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
micturition disorder
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
nephrolithiasis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Endocrine disorders
hyperparathyroidism secondary
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
hyperthyroidism
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Musculoskeletal and connective tissue disorders
arthralgia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	2 / 282 (0.71%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	0	0	0
arthritis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
back pain
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	2 / 282 (0.71%)	1 / 141 (0.71%)	1 / 32 (3.13%)	0 / 62 (0.00%)	1 / 63 (1.59%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	2	1	1	0	1	0	0	0	0	0	0
bursitis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	1 / 18 (5.56%)
occurrences all number	1	1	0	0	0	0	0	0	0	0	1
growing pains
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
muscle twitching
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
musculoskeletal chest pain
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
musculoskeletal stiffness
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
myalgia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	2	0	0	1	0	0	0	0	0	0
neck pain
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0
osteoarthritis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
pain in extremity
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
periarthritis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
rotator cuff syndrome
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
spinal osteoarthritis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
synovial cyst
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Infections and infestations
abscess limb
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0
abscess neck
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
bacterial vaginosis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed ^[9]	1 / 141 (0.71%)	0 / 73 (0.00%)	0 / 21 (0.00%)	0 / 28 (0.00%)	0 / 38 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 45 (2.22%)	0 / 43 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	1	0	0
bronchitis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	2 / 282 (0.71%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	0	0	0
covid-19
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	5 / 282 (1.77%)	3 / 141 (2.13%)	1 / 32 (3.13%)	2 / 62 (3.23%)	8 / 63 (12.70%)	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	4 / 96 (4.17%)	2 / 106 (1.89%)	1 / 18 (5.56%)
occurrences all number	5	3	1	2	9	0	1	0	4	2	1
cellulitis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	1	0
chest wall abscess
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0
conjunctivitis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	21 / 282 (7.45%)	4 / 141 (2.84%)	1 / 32 (3.13%)	0 / 62 (0.00%)	1 / 63 (1.59%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	9 / 96 (9.38%)	5 / 106 (4.72%)	1 / 18 (5.56%)
occurrences all number	23	4	1	0	1	0	0	0	11	6	1
conjunctivitis bacterial
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	2 / 96 (2.08%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	0	0
conjunctivitis viral
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
ear infection
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
ecthyma
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
eczema herpeticum
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	1 / 32 (3.13%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	1	0	0	0	0	0	0	0	0
endophthalmitis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
folliculitis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	3 / 282 (1.06%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	3	1	0	0	0	0	0	0	1	0	0
fungal skin infection
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	1 / 18 (5.56%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1
furuncle
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	2 / 141 (1.42%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	3	0	0	0	0	0	0	0	0	0
gastroenteritis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	2 / 282 (0.71%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	3	0	0	0	0	0	0	0	0	0	0
gastroenteritis viral
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	2 / 282 (0.71%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	0	0	0
genital herpes simplex
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	1 / 18 (5.56%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	1
gingivitis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
helicobacter infection
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
herpes dermatitis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	2 / 106 (1.89%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	2	0
herpes simplex
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
herpes zoster
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
impetigo
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	4 / 282 (1.42%)	2 / 141 (1.42%)	0 / 32 (0.00%)	1 / 62 (1.61%)	1 / 63 (1.59%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	4	2	0	2	1	0	0	0	1	0	0
infected cyst
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	1 / 18 (5.56%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1
influenza
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	1 / 32 (3.13%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0	0	0	0
labyrinthitis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	1 / 32 (3.13%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	1	0
localised infection
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
lower respiratory tract infection
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
myringitis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
nasopharyngitis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	11 / 282 (3.90%)	4 / 141 (2.84%)	2 / 32 (6.25%)	2 / 62 (3.23%)	6 / 63 (9.52%)	0 / 4 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	2 / 96 (2.08%)	4 / 106 (3.77%)	0 / 18 (0.00%)
occurrences all number	11	4	2	2	6	0	1	1	2	5	0
ophthalmic herpes simplex
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
oral herpes
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	9 / 282 (3.19%)	5 / 141 (3.55%)	0 / 32 (0.00%)	1 / 62 (1.61%)	2 / 63 (3.17%)	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	3 / 96 (3.13%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	9	10	0	1	2	0	1	0	4	1	0
otitis media
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	1	0	0
paronychia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
peritonsillar abscess
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
pertussis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
pharyngitis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
pharyngitis streptococcal
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
pneumonia aspiration
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
postoperative wound infection
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
respiratory tract infection viral
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
secondary syphilis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
sinusitis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	2 / 63 (3.17%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	0	0	0
skin infection
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	2 / 141 (1.42%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	2	0	0	0	0	0	0	0	0	0
tinea capitis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
tinea cruris
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
tinea versicolour
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
tonsillitis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	2 / 141 (1.42%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	2 / 96 (2.08%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	1	2	0	0	0	0	1	1	2	1	0
tooth abscess
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	2 / 106 (1.89%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	2	0
tooth infection
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	1 / 18 (5.56%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	1
upper respiratory tract infection
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	2 / 141 (1.42%)	3 / 32 (9.38%)	1 / 62 (1.61%)	1 / 63 (1.59%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	1	3	3	1	1	0	0	0	0	1	0
urinary tract infection
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	1 / 141 (0.71%)	2 / 32 (6.25%)	0 / 62 (0.00%)	1 / 63 (1.59%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	1 / 106 (0.94%)	1 / 18 (5.56%)
occurrences all number	1	1	2	0	1	0	0	0	1	1	1
vaginal infection
alternative dictionary used: MedDRA 24.1
subjects affected / exposed ^[10]	0 / 141 (0.00%)	1 / 73 (1.37%)	0 / 21 (0.00%)	0 / 28 (0.00%)	0 / 38 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 45 (0.00%)	0 / 43 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
viral pericarditis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
viral upper respiratory tract infection
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	1	0	0	0	0	0	0	0
vulvovaginal candidiasis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed ^[11]	2 / 141 (1.42%)	0 / 73 (0.00%)	0 / 21 (0.00%)	0 / 28 (0.00%)	1 / 38 (2.63%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 45 (0.00%)	0 / 43 (0.00%)	0 / 5 (0.00%)
occurrences all number	2	0	0	0	1	0	0	0	0	0	0
Metabolism and nutrition disorders
decreased appetite
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
dehydration
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	1	0	0	0	0	0	0	0
dyslipidaemia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 96 (1.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
hypercholesterolaemia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
hyperlipidaemia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
hypokalaemia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 282 (0.35%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
obesity
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	0 / 141 (0.00%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
vitamin d deficiency
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 282 (0.00%)	1 / 141 (0.71%)	0 / 32 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 96 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0

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

16 Oct 2019

• Clarification of primary, co-primary and secondary endpoints to be analyzed for the FDA and EMEA • Updated inclusion criterion 10 for contraceptive use after last dose of study drug (increased from 17 to 18 weeks) • Added inclusion criterion 11 to require male patients to use an effective method of contraception if sexually active with a female of child-bearing potential. • Other minor clarifications and editorial changes.

20 May 2020

• Added hormone testing to adolescent patients • Removed requirement for TB screening serology at screening visit. • Added PK sample at Week 4 • Clarifications on analysis timing, study procedures and protocol wording.

Were there any global interruptions to the trial? Yes

Date	Interruption	Restart date
24 Mar 2020	Global enrollment hold on new patient screening and enrollment.	28 May 2020

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 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL TO EVALUATE THE EFFICACY AND SAFETY OF LEBRIKIZUMAB IN PATIENTS WITH MODERATE-TO-SEVERE ATOPIC DERMATITIS

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Participants With an Investigator Global Assessment (IGA) Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 16

Primary: Percentage of Participants With an Investigator Global Assessment (IGA) Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 16

Primary: Percentage of Participants Achieving Eczema Area And Severity Index (EASI-75) (≥75% Reduction in EASI Score) From Baseline to Week 16

Primary: Percentage of Participants Achieving Eczema Area And Severity Index (EASI-75) (≥75% Reduction in EASI Score) From Baseline to Week 16

Secondary: Percentage of Participants With an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 2

Secondary: Percentage of Participants With an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 2

Secondary: Percentage of Participants With an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 4

Secondary: Percentage of Participants With an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 4

Secondary: Percentage of Participants With an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 16 in Adults

Secondary: Percentage of Participants With an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 16 in Adults

Secondary: Percentage of Participants Achieving EASI-90 (≥90% Reduction in EASI Score) From Baseline to Week 16

Secondary: Percentage of Participants Achieving EASI-90 (≥90% Reduction in EASI Score) From Baseline to Week 16

Secondary: Percent Change in Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16

Secondary: Percent Change in Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16

Secondary: Percentage of Participants With a Pruritus NRS Score of ≥4-points at Baseline Who Achieve a ≥4-point Reduction in Pruritus NRS Score From Baseline to Week 16

Secondary: Percentage of Participants With a Pruritus NRS Score of ≥4-points at Baseline Who Achieve a ≥4-point Reduction in Pruritus NRS Score From Baseline to Week 16

Secondary: Percentage of Participants With a Pruritus NRS Score of ≥5-points at Baseline Who Achieve a ≥4-point Reduction in Pruritus NRS Score From Baseline to Week 16

Secondary: Percentage of Participants With a Pruritus NRS Score of ≥5-points at Baseline Who Achieve a ≥4-point Reduction in Pruritus NRS Score From Baseline to Week 16

Secondary: Percent Change in EASI Score From Baseline to Week 16

Secondary: Percent Change in EASI Score From Baseline to Week 16

Secondary: Change From Baseline in Percent Body Surface Area (BSA) at Week 16

Secondary: Change From Baseline in Percent Body Surface Area (BSA) at Week 16

Secondary: Percentage of Participants Achieving EASI-90 From Baseline to Week 4

Secondary: Percentage of Participants Achieving EASI-90 From Baseline to Week 4

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

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

Secondary: Percentage of Participants Achieving ≥4 Point Improvement in DLQI From Baseline to Week 16

Secondary: Percentage of Participants Achieving ≥4 Point Improvement in DLQI From Baseline to Week 16

Secondary: Percentage of Participants With a DLQI Total Score of ≥4-point at Baseline Achieving ≥4-point Improvement in DLQI From Baseline to Week 16

Secondary: Percentage of Participants With a DLQI Total Score of ≥4-point at Baseline Achieving ≥4-point Improvement in DLQI From Baseline to Week 16

Secondary: Percent Change in Sleep-loss Score From Baseline to Week 16

Secondary: Percent Change in Sleep-loss Score From Baseline to Week 16

Secondary: Change From Baseline in Sleep-loss Score at Week 16

Secondary: Change From Baseline in Sleep-loss Score at Week 16

Secondary: Percentage of Participants With a Sleep-loss Score ≥2 Points at Baseline Who Achieve a ≥2 Points Reduction From Baseline at Week 16

Secondary: Percentage of Participants With a Sleep-loss Score ≥2 Points at Baseline Who Achieve a ≥2 Points Reduction From Baseline at Week 16

Secondary: Percentage of Participants With a Pruritus NRS Score of ≥4 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 1

Secondary: Percentage of Participants With a Pruritus NRS Score of ≥4 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 1

Secondary: Percentage of Participants With a Pruritus NRS Score of ≥4 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 2

Secondary: Percentage of Participants With a Pruritus NRS Score of ≥4 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 2

Secondary: Percentage of Participants With a Pruritus NRS Score of ≥4 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 4

Secondary: Percentage of Participants With a Pruritus NRS Score of ≥4 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 4

Secondary: Percentage of Participants With a Pruritus NRS Score of ≥5 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 1

Secondary: Percentage of Participants With a Pruritus NRS Score of ≥5 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 1

Secondary: Percentage of Participants With a Pruritus NRS Score of ≥5 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 2

Secondary: Percentage of Participants With a Pruritus NRS Score of ≥5 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 2

Secondary: Percentage of Participants With a Pruritus NRS Score of ≥5 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 4

Secondary: Percentage of Participants With a Pruritus NRS Score of ≥5 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 4

Secondary: Percent Change in SCORing Atopic Dermatitis (SCORAD) From Baseline to Week 16

Secondary: Percent Change in SCORing Atopic Dermatitis (SCORAD) From Baseline to Week 16

Secondary: Change From Baseline in European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) at Week 16 - Health State Index

Secondary: Change From Baseline in European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) at Week 16 - Health State Index

Secondary: Change From Baseline in EQ-5D-5L at Week 16 - Visual Analog Scale (VAS)

Secondary: Change From Baseline in EQ-5D-5L at Week 16 - Visual Analog Scale (VAS)

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

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

Secondary: Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety at Week 16 - Adolescents

Secondary: Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety at Week 16 - Adolescents

Secondary: Change From Baseline in PROMIS Depression at Week 16 - Adolescent

Secondary: Change From Baseline in PROMIS Depression at Week 16 - Adolescent

Secondary: Change From Baseline in PROMIS Anxiety at Week 16 - Adults

Secondary: Change From Baseline in PROMIS Anxiety at Week 16 - Adults

Secondary: Change From Baseline in PROMIS Depression at Week 16 - Adults

Secondary: Change From Baseline in PROMIS Depression at Week 16 - Adults

Secondary: Change From Baseline in Asthma Control Questionnaire (ACQ-5) Score at Week 16 in Participants Who Have Self-Reported Comorbid Asthma

Secondary: Change From Baseline in Asthma Control Questionnaire (ACQ-5) Score at Week 16 in Participants Who Have Self-Reported Comorbid Asthma

Secondary: Change From Baseline in Children’s Dermatology Life Quality Index (CDLQI) at Week 16 - Adolescents

Secondary: Change From Baseline in Children’s Dermatology Life Quality Index (CDLQI) at Week 16 - Adolescents

Secondary: Pharmacokinetics (PK): Average Serum Concentration of Lebrikizumab at Week 52

Secondary: Pharmacokinetics (PK): Average Serum Concentration of Lebrikizumab at Week 52

Clinical Trial Results:
A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL TO EVALUATE THE EFFICACY AND SAFETY OF LEBRIKIZUMAB IN PATIENTS WITH MODERATE-TO-SEVERE ATOPIC DERMATITIS