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Clinical Trial Results:
A Multicenter, Long-Term Extension Study of 104 Weeks, Including a Double-Blind, Placebo-Controlled 40-Week Randomized Withdrawal-Retreatment Period, to Evaluate the Maintenance of Treatment Effect of Ixekizumab (LY2439821) in Patients with Axial Spondyloarthritis

Summary
EudraCT number	2016-002634-69
Trial protocol	ES HU NL FI PL AT DE IT
Global end of trial date	27 May 2021

Results information
Results version number	v2(current)
This version publication date	28 May 2022
First version publication date	10 Jun 2021
Other versions	v1
Version creation reason	New data added to full data set LPV Results

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

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Trial information

Top of page

Sponsor protocol code

I1F-MC-RHBY

ISRCTN number

US NCT number

NCT03129100

WHO universal trial number (UTN)

Other trial identifiers

Trial Number: 16181

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

27 May 2021

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

27 May 2021

Was the trial ended prematurely?

Main objective of the trial

The purpose of this study is to evaluate, in participants having achieved a state of sustained remission, if the ixekizumab treatment groups are superior to the placebo group in maintaining response during the randomized withdrawal-retreatment period in participants with axial spondyloarthritis.

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

09 May 2017

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 34

Country: Number of subjects enrolled

Romania: 5

Country: Number of subjects enrolled

Hungary: 7

Country: Number of subjects enrolled

United States: 61

Country: Number of subjects enrolled

Czechia: 88

Country: Number of subjects enrolled

Japan: 22

Country: Number of subjects enrolled

United Kingdom: 12

Country: Number of subjects enrolled

Spain: 10

Country: Number of subjects enrolled

Russian Federation: 66

Country: Number of subjects enrolled

Canada: 11

Country: Number of subjects enrolled

Netherlands: 3

Country: Number of subjects enrolled

Korea, Republic of: 81

Country: Number of subjects enrolled

Austria: 3

Country: Number of subjects enrolled

Taiwan: 44

Country: Number of subjects enrolled

Finland: 9

Country: Number of subjects enrolled

Brazil: 23

Country: Number of subjects enrolled

Poland: 160

Country: Number of subjects enrolled

Italy: 1

Country: Number of subjects enrolled

Mexico: 104

Country: Number of subjects enrolled

Israel: 10

Country: Number of subjects enrolled

France: 10

Country: Number of subjects enrolled

Germany: 9

Worldwide total number of subjects

773

EEA total number of subjects

317

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)

737

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Lead-In: 24 weeks (Week 0 to 24) Extension Period including Double-Blind, Placebo-Controlled, Randomized Withdrawal-Retreatment (RWR): 40 weeks (Week 24 to 64) Long-Term Extension Period: 40 weeks (Week 64 to 104) Post-Treatment Follow-Up: at least 12 weeks and up to 24 weeks after the date of the participant's ETV or last regularly scheduled.

Screening details

In Period 2, participants (pts) who did not achieve sustained remission were assigned to Group A, pts who did achieve sustained remission were assigned to Group B (Randomized Withdrawal Extension(RWE)) and were randomized 2:1 to either IXE or Placebo. pts who experienced a flare in group B were retreated with IXE in Retreatment Extension Period.

Period 1 title

Lead-In Period (Period 1)

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

IXE80Q4W-Lead-in Period

Arm description

Participants received 80 milligram (mg) of Ixekizumab (IXE) subcutaneously (SC) every four weeks (Q4W) for up to week 24.

Arm type

Experimental

Investigational medicinal product name

IXE80Q4W

Investigational medicinal product code

Other name

Ixekizumab; LY2439821

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received 80 mg of Ixekizumab subcutaneously every four weeks.

IXE80Q2W-Lead-in Period

Arm description

Participants received 80 mg of Ixekizumab subcutaneously every two weeks (Q2W) for up to week 24.

Arm type

Experimental

Investigational medicinal product name

IXE80Q2W

Investigational medicinal product code

Other name

Ixekizumab; LY2439821

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received 80 mg of Ixekizumab subcutaneously every two weeks.

Number of subjects in period 1	IXE80Q4W-Lead-in Period	IXE80Q2W-Lead-in Period
Started	350	423
Completed	335	406
Not completed	15	17
Consent withdrawn by subject	8	8
Adverse event, non-fatal	2	6
Lost to follow-up	2	-
Check with team	-	1
Lack of efficacy	3	2

Period 2 title

Extension Period (Period 2A)

Is this the baseline period?

Yes ^[1]

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer

Are arms mutually exclusive

IXE80Q4W-Group A Extension Period

Arm description

Participants continued to receive uninterrupted Ixekizumab 80 mg Q4W subcutaneous dose during the extension period.

Arm type

Placebo

Investigational medicinal product name

IXE80Q4W

Investigational medicinal product code

Other name

Ixekizumab; LY2439821

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received 80 mg of Ixekizumab subcutaneously every four weeks.

IXE80Q2W-Group A Extension Period

Arm description

Participants continued to receive uninterrupted Ixekizumab 80 mg Q2W subcutaneous dose during the extension period.

Arm type

Experimental

Investigational medicinal product name

IXE80Q2W

Investigational medicinal product code

Other name

Ixekizumab; LY2439821

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received 80 mg of Ixekizumab subcutaneously every two weeks.

Investigational medicinal product name

IXE80Q2W

Investigational medicinal product code

Other name

Ixekizumab; LY2439821

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received 80 mg of Ixekizumab subcutaneously every two weeks.

IXE80Q4W-Group B-Randomized Withdrawal Extension Period

Arm description

Participants in the Ixekizumab 80 mg Q4W treatment group (Lead-in) were re randomized to receive Ixekizumab 80 mg Q4W subcutaneous dose at Week 24 in the randomized withdrawal extension period.

Arm type

Experimental

Investigational medicinal product name

IXE80Q4W

Investigational medicinal product code

Other name

Ixekizumab; LY2439821

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received 80 mg of Ixekizumab subcutaneously every four weeks.

IXE80Q2W-Group B-Randomized Withdrawal Extension Period

Arm description

Participants in the Ixekizumab 80 mg Q2W treatment group (Lead-in) were re randomized to receive subcutaneous dose of Ixekizumab 80 mg Q2W at Week 24 in the randomized withdrawal extension period.

Arm type

Experimental

Investigational medicinal product name

IXE80Q2W

Investigational medicinal product code

Other name

Ixekizumab; LY2439821

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received 80 mg of Ixekizumab subcutaneously every two weeks.

Placebo-Group B-Randomized Withdrawal Extension Period

Arm description

Participants were re-randomized to receive subcutaneous dose of placebo at Week 24 in the randomized withdrawal extension period.

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

Participants were randomized to receive subcutaneous injection of placebo.

Notes
[1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period.
Justification: Baseline analysis population is based on efficacy population of all randomized participants (Extension Period).

Number of subjects in period 2	IXE80Q4W-Group A Extension Period	IXE80Q2W-Group A Extension Period	IXE80Q4W-Group B-Randomized Withdrawal Extension Period	IXE80Q2W-Group B-Randomized Withdrawal Extension Period	Placebo-Group B-Randomized Withdrawal Extension Period
Started	255	318	48	54	53
Completed	234	312	42	45	32
Not completed	21	6	6	9	21
Adverse event, serious fatal	1	-	-	-	-
Consent withdrawn by subject	13	5	1	1	2
Physician decision	1	-	-	-	-
Adverse event, non-fatal	2	1	-	2	-
Lost to follow-up	2	-	-	-	-
Experienced Flare and retreated	-	-	5	6	19
Lack of efficacy	2	-	-	-	-

Period 3 title

Retreatment Extension Period (Period 2)

Is this the baseline period?

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

IXE80Q2W/IXE80Q2W-retreatment Extension Period

Arm description

Participants in Group B who received Ixekizumab 80 mg Q2W in Period 2 and experienced a flare were retreated with subcutaneous dose of Ixekizumab 80 mg Q2W during the retreatment long-term extension period.

Arm type

Experimental

Investigational medicinal product name

IXE80Q2W

Investigational medicinal product code

Other name

Ixekizumab; LY2439821

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received 80 mg of Ixekizumab subcutaneously every two weeks.

IXE80Q4W/IXE80Q4W-Retreatment Extension Period

Arm description

Participants in Group B who received Ixekizumab 80 mg Q4W in Period 2 and experienced a flare were retreated with subcutaneous dose of Ixekizumab 80 mg Q4W during the retreatment long term extension period.

Arm type

Experimental

Investigational medicinal product name

IXE80Q4W

Investigational medicinal product code

Other name

Ixekizumab; LY2439821

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received 80 mg of Ixekizumab subcutaneously every four weeks.

PBO/IXE80Q2W-Retreatment Extension Period

Arm description

Participants in Group B who received placebo in Period 2 and experienced a flare were retreated with subcutaneous dose of Ixekizumab 80 mg Q2W during the retreatment long term extension period.

Arm type

Experimental

Investigational medicinal product name

IXE80Q2W

Investigational medicinal product code

Other name

Ixekizumab; LY2439821

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received 80 mg of Ixekizumab subcutaneously every two weeks.

PBO/IXE80Q4W-Retreatment Extension Period

Arm description

Participants in Group B who received placebo in Period 2 and experienced a flare were retreated with subcutaneous dose of Ixekizumab 80 mg Q4W during the retreatment long term extension period.

Arm type

Experimental

Investigational medicinal product name

IXE80Q4W

Investigational medicinal product code

Other name

Ixekizumab; LY2439821

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received 80 mg of Ixekizumab subcutaneously every four weeks.

Number of subjects in period 3	IXE80Q2W/IXE80Q2W-retreatment Extension Period	IXE80Q4W/IXE80Q4W-Retreatment Extension Period	PBO/IXE80Q2W-Retreatment Extension Period	PBO/IXE80Q4W-Retreatment Extension Period
Started	6	5	9	10
Completed	6	5	8	10
Not completed	0	0	1	0
Consent withdrawn by subject	-	-	1	-

Period 4 title

Period3-Long-Term Extension Period A & B

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

IXE80Q2W-group A Long-term Extension Period

Arm description

Participants from "IXE80Q2W group A extension period" continued to receive same treatment that they were receiving at the end of Period 2.

Arm type

Experimental

Investigational medicinal product name

IXE80Q2W

Investigational medicinal product code

Other name

Ixekizumab; LY2439821

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received 80 mg of Ixekizumab subcutaneously every two weeks.

IXE80Q4W-group A Long-term Extension Period

Arm description

Participants from "IXE80Q4W group A extension period" continued to receive same treatment that they were receiving at the end of Period 2.

Arm type

Experimental

Investigational medicinal product name

IXE80Q4W

Investigational medicinal product code

Other name

Ixekizumab; LY2439821

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received 80 mg of Ixekizumab subcutaneously every four weeks.

IXE80Q2W-randomized Withdrawal Long-term Extension Period

Arm description

Participants from "IXE80Q2W-Group B-Randomized Withdrawal Extension Period" continued to receive same treatment that they were receiving at the end of Period 2.

Arm type

Experimental

Investigational medicinal product name

IXE80Q2W

Investigational medicinal product code

Other name

Ixekizumab; LY2439821

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received 80 mg of Ixekizumab subcutaneously every two weeks.

IXE80Q4W-randomized Withdrawal Long-term Extension Period

Arm description

Participants from "IXE80Q4W-Group B-Randomized Withdrawal Extension Period" continued to receive same treatment that they were receiving at the end of Period 2.

Arm type

Experimental

Investigational medicinal product name

IXE80Q4W

Investigational medicinal product code

Other name

Ixekizumab; LY2439821

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received 80 mg of Ixekizumab subcutaneously every four weeks.

PBO-randomized Withdrawal Long-term Extension Period

Arm description

Participants from "Placebo-Group B-Randomized Withdrawal Extension Period" continued to receive same treatment that they were receiving at the end of Period 2.

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

Participants were randomized to receive subcutaneous injection of placebo.

Number of subjects in period 4	IXE80Q2W-group A Long-term Extension Period	IXE80Q4W-group A Long-term Extension Period	IXE80Q2W-randomized Withdrawal Long-term Extension Period	IXE80Q4W-randomized Withdrawal Long-term Extension Period	PBO-randomized Withdrawal Long-term Extension Period
Started	306	177	45	42	30
Completed	287	146	40	37	21
Not completed	19	31	5	5	9
Consent withdrawn by subject	12	7	4	2	-
Adverse event, non-fatal	6	-	-	-	-
Lost to follow-up	1	-	1	1	-
Escalated to IXE80Q2W	-	24	-	2	8
Lack of efficacy	-	-	-	-	1

Period 5 title

Period 3 (Flare)

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

IXE80Q2W/IXE80Q2W-retreatment Long-term Extension Period

Arm description

Participants in Group B who received Ixekizumab 80 mg Q2W in Period 3 and experienced a flare were retreated with subcutaneous dose of Ixekizumab 80 mg Q2W during the retreatment long-term extension period.

Arm type

Experimental

Investigational medicinal product name

IXE80Q2W

Investigational medicinal product code

Other name

Ixekizumab; LY2439821

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received 80 mg of Ixekizumab subcutaneously every two weeks.

IXE80Q4W/IXE80Q4W-retreatment Long-term Extension Period

Arm description

Participants in Group B who received Ixekizumab 80 mg Q4W in Period 3 and experienced a flare were retreated with subcutaneous dose of Ixekizumab 80 mg Q4W during the retreatment long term extension period.

Arm type

Experimental

Investigational medicinal product name

IXE80Q4W

Investigational medicinal product code

Other name

Ixekizumab; LY2439821

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received 80 mg of Ixekizumab subcutaneously every four weeks.

PBO/IXE80Q2W-retreatment Long-term Extension Period

Arm description

Participants in Group B who received placebo in Period 3 and experienced a flare were retreated with subcutaneous dose of Ixekizumab 80 mg Q2W during the retreatment long term extension period.

Arm type

Experimental

Investigational medicinal product name

IXE80Q2W

Investigational medicinal product code

Other name

Ixekizumab; LY2439821

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received 80 mg of Ixekizumab subcutaneously every two weeks.

PBO/IXE80Q4W-retreatment Long-term Extension Period

Arm description

Participants in Group B who experienced a flare were retreated with subcutaneous dose of Ixekizumab 80 mg Q4W during the retreatment long term extension period.

Arm type

Experimental

Investigational medicinal product name

IXE80Q4W

Investigational medicinal product code

Other name

Ixekizumab; LY2439821

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received 80 mg of Ixekizumab subcutaneously every four weeks.

Number of subjects in period 5	IXE80Q2W/IXE80Q2W-retreatment Long-term Extension Period	IXE80Q4W/IXE80Q4W-retreatment Long-term Extension Period	PBO/IXE80Q2W-retreatment Long-term Extension Period	PBO/IXE80Q4W-retreatment Long-term Extension Period
Started	6	4	11	15
Completed	6	2	11	12
Not completed	0	2	0	3
Escalated to IXE80Q2W	-	2	-	3

Period 6 title

Period 3 (Dose Escalation)

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

IXE80Q4W-group A Escalation Period

Arm description

Participants in Group A receiving ixekizumab 80 mg Q4W escalated to ixekizumab 80 mg Q2W in Period 3.

Arm type

Experimental

Investigational medicinal product name

IXE80Q4W

Investigational medicinal product code

Other name

Ixekizumab; LY2439821

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received 80 mg of Ixekizumab subcutaneously every four weeks.

IXE80Q4W-randomized Withdrawal Escalation Period

Arm description

Participants in Group B receiving Ixekizumab 80 mg Q4W escalated to ixekizumab 80 mg Q2W.

Arm type

Experimental

Investigational medicinal product name

IXE80Q4W

Investigational medicinal product code

Other name

Ixekizumab; LY2439821

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received 80 mg of Ixekizumab subcutaneously every four weeks.

PBO-randomized Withdrawal Escalation Period

Arm description

Participants in Group B, who received PBO, experienced a flare and retreated with Ixekizumab 80 mg Q4W, escalated to ixekizumab 80 mg Q2W.

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

Participants were randomized to receive subcutaneous injection of placebo.

Number of subjects in period 6	IXE80Q4W-group A Escalation Period	IXE80Q4W-randomized Withdrawal Escalation Period	PBO-randomized Withdrawal Escalation Period
Started	77	5	4
Completed	73	5	4
Not completed	4	0	0
Consent withdrawn by subject	2	-	-
Physician decision	1	-	-
Lack of efficacy	1	-	-

Period 7 title

Period 4 (Post Treatment Follow-up)

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

PBO-follow-up Period

Arm description

Participants did not receive any intervention during Follow-up period.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

IXE80Q4W-follow-up Period

Arm description

Participants did not receive any intervention during Follow-up period.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

IXE80Q2W-follow-up Period

Arm description

Participants did not receive any intervention during Follow-up period.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Number of subjects in period 7	PBO-follow-up Period	IXE80Q4W-follow-up Period	IXE80Q2W-follow-up Period
Started	25	223	453
Completed	22	198	411
Not completed	3	25	42
Adverse event, serious fatal	-	1	-
Consent withdrawn by subject	3	20	37
COVID 19 restrictions	-	2	-
Unknown	-	-	2
Missed to follow-up	-	-	1
Lost to follow-up	-	2	2

Baseline characteristics

Top of page

Reporting group title

IXE80Q4W-Group A Extension Period

Reporting group description

Participants continued to receive uninterrupted Ixekizumab 80 mg Q4W subcutaneous dose during the extension period.

Reporting group title

IXE80Q2W-Group A Extension Period

Reporting group description

Participants continued to receive uninterrupted Ixekizumab 80 mg Q2W subcutaneous dose during the extension period.

Reporting group title

IXE80Q4W-Group B-Randomized Withdrawal Extension Period

Reporting group description

Participants in the Ixekizumab 80 mg Q4W treatment group (Lead-in) were re randomized to receive Ixekizumab 80 mg Q4W subcutaneous dose at Week 24 in the randomized withdrawal extension period.

Reporting group title

IXE80Q2W-Group B-Randomized Withdrawal Extension Period

Reporting group description

Participants in the Ixekizumab 80 mg Q2W treatment group (Lead-in) were re randomized to receive subcutaneous dose of Ixekizumab 80 mg Q2W at Week 24 in the randomized withdrawal extension period.

Reporting group title

Placebo-Group B-Randomized Withdrawal Extension Period

Reporting group description

Participants were re-randomized to receive subcutaneous dose of placebo at Week 24 in the randomized withdrawal extension period.

Notes
[1] - The number of subjects reported to be in the baseline period is not equal to the worldwide number of subjects enrolled in the trial. It is expected that these numbers will be the same.
Justification: Baseline characteristics presented only for treatment group.

Reporting group values	IXE80Q4W-Group A Extension Period	IXE80Q2W-Group A Extension Period	IXE80Q4W-Group B-Randomized Withdrawal Extension Period	IXE80Q2W-Group B-Randomized Withdrawal Extension Period	Placebo-Group B-Randomized Withdrawal Extension Period	Total
Number of subjects	255	318	48	54	53	728
Age categorical
Units: Subjects
<=18 years	0	0	0	0	0	0
Between 18 and 65 years	240	302	48	53	52	695
>=65 years	15	16	0	1	1	33
Gender categorical
Units: Subjects
Female	68	95	10	14	15	202
Male	187	223	38	40	38	526
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	61	86	7	14	11	179
Not Hispanic or Latino	166	204	31	35	39	475
Unknown or Not Reported	28	28	10	5	3	74
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	14	11	2	5	4	36
Asian	54	50	15	15	13	147
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0
Black or African American	0	2	0	0	0	2
White	183	247	31	31	35	527
More than one race	3	8	0	3	1	15
Unknown or Not Reported	1	0	0	0	0	1
Region of Enrollment
Units: Subjects
Argentina	11	18	1	1	2	33
Romania	1	3	0	1	0	5
Hungary	3	2	1	1	0	7
United States	14	30	1	3	2	50
Czechia	37	35	5	4	4	85
Japan	7	9	1	3	1	21
United Kingdom	4	6	0	1	0	11
Spain	5	4	0	1	0	10
Russia	16	30	6	7	6	65
Canada	3	2	1	0	2	8
Netherlands	0	2	0	0	0	2
South Korea	28	23	10	7	8	76
Austria	1	1	0	1	0	3
Taiwan	17	16	3	5	2	43
Finland	0	5	0	1	2	8
Brazil	7	16	0	0	0	23
Poland	50	67	13	7	13	150
Italy	0	1	0	0	0	1
Mexico	40	38	5	11	8	102
Israel	5	3	0	0	1	9
France	4	4	0	0	0	8
Germany	2	3	1	0	2	8

End points

Top of page

Reporting group title

IXE80Q4W-Lead-in Period

Reporting group description

Participants received 80 milligram (mg) of Ixekizumab (IXE) subcutaneously (SC) every four weeks (Q4W) for up to week 24.

Reporting group title

IXE80Q2W-Lead-in Period

Reporting group description

Participants received 80 mg of Ixekizumab subcutaneously every two weeks (Q2W) for up to week 24.

Reporting group title

IXE80Q4W-Group A Extension Period

Reporting group description

Participants continued to receive uninterrupted Ixekizumab 80 mg Q4W subcutaneous dose during the extension period.

Reporting group title

IXE80Q2W-Group A Extension Period

Reporting group description

Participants continued to receive uninterrupted Ixekizumab 80 mg Q2W subcutaneous dose during the extension period.

Reporting group title

IXE80Q4W-Group B-Randomized Withdrawal Extension Period

Reporting group description

Participants in the Ixekizumab 80 mg Q4W treatment group (Lead-in) were re randomized to receive Ixekizumab 80 mg Q4W subcutaneous dose at Week 24 in the randomized withdrawal extension period.

Reporting group title

IXE80Q2W-Group B-Randomized Withdrawal Extension Period

Reporting group description

Participants in the Ixekizumab 80 mg Q2W treatment group (Lead-in) were re randomized to receive subcutaneous dose of Ixekizumab 80 mg Q2W at Week 24 in the randomized withdrawal extension period.

Reporting group title

Placebo-Group B-Randomized Withdrawal Extension Period

Reporting group description

Participants were re-randomized to receive subcutaneous dose of placebo at Week 24 in the randomized withdrawal extension period.

Reporting group title

IXE80Q2W/IXE80Q2W-retreatment Extension Period

Reporting group description

Reporting group title

IXE80Q4W/IXE80Q4W-Retreatment Extension Period

Reporting group description

Reporting group title

PBO/IXE80Q2W-Retreatment Extension Period

Reporting group description

Participants in Group B who received placebo in Period 2 and experienced a flare were retreated with subcutaneous dose of Ixekizumab 80 mg Q2W during the retreatment long term extension period.

Reporting group title

PBO/IXE80Q4W-Retreatment Extension Period

Reporting group description

Participants in Group B who received placebo in Period 2 and experienced a flare were retreated with subcutaneous dose of Ixekizumab 80 mg Q4W during the retreatment long term extension period.

Reporting group title

IXE80Q2W-group A Long-term Extension Period

Reporting group description

Participants from "IXE80Q2W group A extension period" continued to receive same treatment that they were receiving at the end of Period 2.

Reporting group title

IXE80Q4W-group A Long-term Extension Period

Reporting group description

Participants from "IXE80Q4W group A extension period" continued to receive same treatment that they were receiving at the end of Period 2.

Reporting group title

IXE80Q2W-randomized Withdrawal Long-term Extension Period

Reporting group description

Participants from "IXE80Q2W-Group B-Randomized Withdrawal Extension Period" continued to receive same treatment that they were receiving at the end of Period 2.

Reporting group title

IXE80Q4W-randomized Withdrawal Long-term Extension Period

Reporting group description

Participants from "IXE80Q4W-Group B-Randomized Withdrawal Extension Period" continued to receive same treatment that they were receiving at the end of Period 2.

Reporting group title

PBO-randomized Withdrawal Long-term Extension Period

Reporting group description

Participants from "Placebo-Group B-Randomized Withdrawal Extension Period" continued to receive same treatment that they were receiving at the end of Period 2.

Reporting group title

IXE80Q2W/IXE80Q2W-retreatment Long-term Extension Period

Reporting group description

Reporting group title

IXE80Q4W/IXE80Q4W-retreatment Long-term Extension Period

Reporting group description

Reporting group title

PBO/IXE80Q2W-retreatment Long-term Extension Period

Reporting group description

Participants in Group B who received placebo in Period 3 and experienced a flare were retreated with subcutaneous dose of Ixekizumab 80 mg Q2W during the retreatment long term extension period.

Reporting group title

PBO/IXE80Q4W-retreatment Long-term Extension Period

Reporting group description

Participants in Group B who experienced a flare were retreated with subcutaneous dose of Ixekizumab 80 mg Q4W during the retreatment long term extension period.

Reporting group title

IXE80Q4W-group A Escalation Period

Reporting group description

Participants in Group A receiving ixekizumab 80 mg Q4W escalated to ixekizumab 80 mg Q2W in Period 3.

Reporting group title

IXE80Q4W-randomized Withdrawal Escalation Period

Reporting group description

Participants in Group B receiving Ixekizumab 80 mg Q4W escalated to ixekizumab 80 mg Q2W.

Reporting group title

PBO-randomized Withdrawal Escalation Period

Reporting group description

Participants in Group B, who received PBO, experienced a flare and retreated with Ixekizumab 80 mg Q4W, escalated to ixekizumab 80 mg Q2W.

Reporting group title

PBO-follow-up Period

Reporting group description

Participants did not receive any intervention during Follow-up period.

Reporting group title

IXE80Q4W-follow-up Period

Reporting group description

Participants did not receive any intervention during Follow-up period.

Reporting group title

IXE80Q2W-follow-up Period

Reporting group description

Participants did not receive any intervention during Follow-up period.

Subject analysis set title

Combined IXE

Subject analysis set type

Per protocol

Subject analysis set description

Participants received 80 mg of Ixekizumab subcutaneously (SC) every four weeks (Q4W) and every two weeks (Q2W) during the randomized withdrawal extension period.

Subject analysis set title

Placebo

Subject analysis set type

Per protocol

Subject analysis set description

Participants received placebo subcutaneously during the randomized withdrawal extension period.

Subject analysis set title

IXE80Q4W

Subject analysis set type

Per protocol

Subject analysis set description

Participants received 80 mg of Ixekizumab subcutaneously (SC) every four weeks (Q4W) during the randomized withdrawal extension period.

Subject analysis set title

IXE80Q2W

Subject analysis set type

Per protocol

Subject analysis set description

Participants received 80 mg of Ixekizumab subcutaneously (SC) every two weeks (Q2W) during the randomized withdrawal extension period.

Primary: Percentage of Participants who do not Experience a Flare (Combined Ixekizumab Treatment)

Top of page

End point title

Percentage of Participants who do not Experience a Flare (Combined Ixekizumab Treatment)

End point description

A flare is defined as Ankylosing Spondylitis Disease Activity Score (ASDAS ≥2.1) at 2 consecutive visits, or ASDAS >3.5 at any visit during Period 2. ASDAS is a composite index to assess disease activity in AS. The parameters used for the ASDAS (with high sensitivity C-reactive protein (CRP) as acute phase reactant) are total back pain, patient global, peripheral pain/swelling, duration of morning stiffness and CRP in mg/L. The ASDAScrp is calculated with the following equation: 0.121×total back pain+0.110×patient global+0.073×peripheral pain/swelling+0.058×duration of morning stiffness+0.579×Ln(CRP+1). (CRP is in mg/liter, the range of other variables is from 0(normal) to 10(very severe); Ln represents the natural logarithm). Data from five variables combined to yield a score (0.6361 to no defined upper limit), where higher the score worse the disease activity. APD: pts who achieved a state of sustained remission and were randomized to 40-week double-blind placebo controlled RWR.

End point type

Primary

End point timeframe

Week 64

End point values	Combined IXE	Placebo
Number of subjects analysed	102	53
Units: Percentage of participants
number (not applicable)	83.3	54.7

Who do not Experience a Flare (Combined IXE)

Comparison groups

Placebo v Combined IXE

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.35

Confidence interval

level

95%

sides

2-sided

lower limit

2.03

upper limit

9.35

Secondary: Percentage of Participants who do not Experience a Flare

Top of page

End point title

Percentage of Participants who do not Experience a Flare

End point description

A flare is defined as ASDAS ≥2.1 at 2 consecutive visits or ASDAS >3.5 at any visit during Period 2. ASDAS is a composite index to assess disease activity in AS. The parameters used for the ASDAS (with high sensitivity C-reactive protein (CRP) as acute phase reactant) are total back pain, patient global, peripheral pain/swelling, duration of morning stiffness and CRP in mg/L. The ASDAScrp is calculated with the following equation: 0.121×total back pain+0.110×patient global+0.073×peripheral pain/swelling+0.058×duration of morning stiffness+0.579×Ln(CRP+1) (CRP is in mg/liter, the range of other variables is from 0(normal) to 10(very severe); Ln represents the natural logarithm). Data from five variables combined to yield a score (0.6361 to no defined upper limit), where higher the score worse the disease activity. APD: pts who achieved a state of sustained remission and were randomized to 40-week double-blind placebo controlled RWR period (Group B). Missing data was imputed using NRI.

End point type

Secondary

End point timeframe

Week 64

End point values	Placebo	IXE80Q4W	IXE80Q2W
Number of subjects analysed	53	48	54
Units: Percentage of participants
number (not applicable)	54.7	83.3	83.3

Participants Who do Not Experience a Flare

Comparison groups

IXE80Q4W v Placebo

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.28

Confidence interval

level

95%

sides

2-sided

lower limit

1.66

upper limit

11.03

Participants Who do Not Experience a Flare

Comparison groups

IXE80Q2W v Placebo

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.42

Confidence interval

level

95%

sides

2-sided

lower limit

1.77

upper limit

11.02

Secondary: Change from Baseline in Modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS)

Top of page

End point title

Change from Baseline in Modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS)

End point description

The mSASSS is a four-point scoring system for lateral radiographs of the lumbar and cervical spine and has been shown to reliably track disease progression over time, where: 0 = normal; 1 = sclerosis, squaring or erosion; 2 = syndesmophyte; 3 = bony bridge. By the scoring system of mSASSS of the spinal x-rays, a total of 24 sites were scored on the lateral cervical and lumbar spine: the anterior corners of the vertebrae from lower border of C2 to upper border T1 (inclusive), and from lower border of T12 to upper border of S1 (inclusive). Each corner was scored from 0 to 3, resulting in a range from 0 [no change] to 72 [progression]. APD: Ixekizumab structure population who have been treated with ixekizumab for at least 24 months.

End point type

Secondary

End point timeframe

Baseline, 2 Years (108 Weeks)

End point values	Combined IXE	IXE80Q4W	IXE80Q2W
Number of subjects analysed	230	115	115
Units: Units on a Scale
arithmetic mean (standard deviation)	0.32 ( 1.779 )	0.41 ( 2.102 )	0.23 ( 1.387 )

No statistical analyses for this end point

Secondary: Percentage of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS)20 Response

Top of page

End point title

Percentage of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS)20 Response

End point description

ASAS20 response is defined as a ≥20% improvement and an absolute improvement from baseline of ≥1 units (range 0 to 10) in ≥3 of 4 domains, and no worsening of ≥20% and ≥1 unit in the remaining domain. Patient Global: How active was your spondylitis on average during the last week? score ranges 0 (not active) to 10 (very active). Spinal Pain: How much Pain of your spine due to Ankylosing spondylitis? score ranges 0 (no pain) to 10 (severe pain). Bath Ankylosing Spondylitis Functional Index (BASFI): Participant asked to rate the difficulty associated with 10 individual basic functional activities, response measured on NRS (range 0 to 10) with a higher score indicating worse function. Inflammation based on mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Q5 & Q6 (mean of intensity & duration of stiffness): Score ranges from "0" (none) and "10" (very severe). APD: Participants who achieved a state of sustained remission and randomized to 40-week DBPC RWR period.

End point type

Secondary

End point timeframe

Week 64

End point values	Placebo	IXE80Q4W	IXE80Q2W
Number of subjects analysed	53	48	54
Units: Percentage of participants
number (not applicable)	50.9	81.3	81.5

ASAS20 response

Comparison groups

IXE80Q4W v Placebo

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.51

Confidence interval

level

95%

sides

2-sided

lower limit

1.78

upper limit

11.41

ASAS20 response

Comparison groups

IXE80Q2W v Placebo

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.61

Confidence interval

level

95%

sides

2-sided

lower limit

1.88

upper limit

11.31

Secondary: Percentage of Participants Achieving an ASAS40 Response

Top of page

End point title

Percentage of Participants Achieving an ASAS40 Response

End point description

ASAS40 is defined as a ≥40% improvement and an absolute improvement from baseline of ≥2 units (range of 0 to 10) in at least 3 of the following 4 domains without any worsening in the remaining domain. The following ASAS domains are used: Patient Global: How active was your spondylitis on average during the last week? score ranges 0 (not active) to 10 (very active). Spinal Pain: How much Pain of your spine due to Ankylosing spondylitis? score ranges 0 (no pain) to 10 (severe pain). BASFI: Participant asked to rate the difficulty associated with 10 individual basic functional activities. Participant response was captured using Numeric Rating Scale (NRS) (range 0 to 10) with a higher score indicating worse function. Inflammation based on mean of BASDAI Q5 & Q6 (mean of intensity & duration of stiffness): Score ranges from "0" (none) and "10" (very severe). APD: Participants who achieved a state of sustained remission and were randomized to 40-week DBPLC RWR period.

End point type

Secondary

End point timeframe

Week 64

End point values	Placebo	IXE80Q4W	IXE80Q2W
Number of subjects analysed	53	48	54
Units: Percentage of Participants
number (not applicable)	43.4	79.2	79.6

ASAS40 Response

Comparison groups

IXE80Q4W v Placebo

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

5.17

Confidence interval

level

95%

sides

2-sided

lower limit

2.11

upper limit

12.69

ASAS40 Response

Comparison groups

IXE80Q2W v Placebo

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

5.23

Confidence interval

level

95%

sides

2-sided

lower limit

2.2

upper limit

12.47

Secondary: Percentage of Participants with Change of Ankylosing Spondylitis Disease Activity Score (ASDAS) ≥1.1 Units

Top of page

End point title

Percentage of Participants with Change of Ankylosing Spondylitis Disease Activity Score (ASDAS) ≥1.1 Units

End point description

ASDAS is a composite index to assess disease activity in AS. The parameters used for the ASDAS (with CRP as acute phase reactant) are total back pain, patient global, peripheral pain/swelling, duration of morning stiffness and CRP in mg/L. The ASDAScrp is calculated with the following equation: 0.121×total back pain+0.110×patient global+0.073×peripheral pain/swelling+0.058×duration of morning stiffness +0.579×Ln(CRP+1). (CRP is in mg/liter, the range of other variables is from 0(normal) to 10(very severe); Ln represents the natural logarithm). Data from five variables combined to yield a score (0.6361 to no defined upper limit), where higher the score worse the disease activity. APD: Participants who achieved a state of sustained remission and were randomized to 40-week double-blind placebo controlled RWR period (Group B). Missing data was imputed using the nonresponder imputation (NRI) method.

End point type

Secondary

End point timeframe

Week 64

End point values	Placebo	IXE80Q4W	IXE80Q2W
Number of subjects analysed	53	48	54
Units: Percentage of participants
number (not applicable)	45.3	79.2	74.1

ASDAS ≥1.1 Units

Comparison groups

IXE80Q4W v Placebo

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.6

Confidence interval

level

95%

sides

2-sided

lower limit

1.9

upper limit

11.17

ASDAS ≥1.1 Units

Comparison groups

IXE80Q2W v Placebo

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.55

Confidence interval

level

95%

sides

2-sided

lower limit

1.56

upper limit

8.09

Secondary: Percentage of Participants with Inactive Disease on the ASDAS (<1.3 Units)

Top of page

End point title

Percentage of Participants with Inactive Disease on the ASDAS (<1.3 Units)

End point description

End point type

Secondary

End point timeframe

Week 64

End point values	Placebo	IXE80Q4W	IXE80Q2W
Number of subjects analysed	53	48	54
Units: Percentage of participants
number (not applicable)	24.5	60.4	53.7

ASDAS (<1.3 Units)

Comparison groups

IXE80Q4W v Placebo

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.92

Confidence interval

level

95%

sides

2-sided

lower limit

2.07

upper limit

11.72

ASDAS (<1.3 Units)

Comparison groups

IXE80Q2W v Placebo

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.61

Confidence interval

level

95%

sides

2-sided

lower limit

1.57

upper limit

8.32

Secondary: Change from Baseline in the Individual Components of the ASAS Criteria

Top of page

End point title

Change from Baseline in the Individual Components of the ASAS Criteria

End point description

Patient Global: How active was your spondylitis on average during the last week? score ranges 0 (not active) to 10 (very active). Spinal Pain: How much Pain of your spine due to Ankylosing spondylitis? score ranges 0 (no pain) to 10 (severe pain). BASFI: Participant asked to rate the difficulty associated with 10 individual basic functional activities. Participant response was captured using Numeric Rating Scale (NRS) (range 0 to 10) with a higher score indicating worse function. Inflammation based on Q5 & Q6 mean of BASDAI (mean of intensity & duration of stiffness): Score ranges from "0" (none) and "10" (very severe). LS mean was determined by ANCOVA with treatment, geographic region, originating study, baseline value and Week 24 value as fixed factors. APD:Participants who achieved a state of sustained remission and were randomized to 40-week DBPC RWR. Missing data was imputed using the modified baseline observation carried forward (mBOCF) method.

End point type

Secondary

End point timeframe

Baseline, Week 64

End point values	Placebo	IXE80Q4W	IXE80Q2W
Number of subjects analysed	53	48	54
Units: Units on a scale
least squares mean (standard error)
Patient Global	-3.0 ( 0.36 )	-5.1 ( 0.38 )	-5.0 ( 0.36 )
Spinal Pain	-3.0 ( 0.36 )	-5.1 ( 0.39 )	-4.8 ( 0.37 )
BASFI	-2.79 ( 0.301 )	-4.35 ( 0.316 )	-4.19 ( 0.301 )
Inflammation	-3.03 ( 0.317 )	-5.20 ( 0.336 )	-4.83 ( 0.319 )

ASAS Criteria

Statistical analysis description

Patient Global

Comparison groups

IXE80Q4W v Placebo

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority ^[1]

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2.1

Confidence interval

level

95%

sides

2-sided

lower limit

-3.1

upper limit

-1.1

Variability estimate

Standard error of the mean

Dispersion value

0.51

Notes
[1] - Patient Global

ASAS Criteria

Statistical analysis description

Patient Global

Comparison groups

IXE80Q2W v Placebo

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority ^[2]

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-2.9

upper limit

-1

Variability estimate

Standard error of the mean

Dispersion value

0.49

Notes
[2] - Patient Global

ASAS Criteria

Statistical analysis description

Spinal Pain

Comparison groups

IXE80Q4W v Placebo

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority ^[3]

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2.1

Confidence interval

level

95%

sides

2-sided

lower limit

-3.1

upper limit

-1

Variability estimate

Standard error of the mean

Dispersion value

0.51

Notes
[3] - Spinal Pain

ASAS Criteria

Statistical analysis description

Spinal Pain

Comparison groups

IXE80Q2W v Placebo

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority ^[4]

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.8

Confidence interval

level

95%

sides

2-sided

lower limit

-2.8

upper limit

-0.8

Variability estimate

Standard error of the mean

Dispersion value

0.49

Notes
[4] - Spinal Pain

ASAS Criteria

Statistical analysis description

BASFI

Comparison groups

IXE80Q4W v Placebo

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority ^[5]

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.55

Confidence interval

level

95%

sides

2-sided

lower limit

-2.39

upper limit

-0.72

Variability estimate

Standard error of the mean

Dispersion value

0.421

Notes
[5] - BASFI

ASAS Criteria

Statistical analysis description

BASFI

Comparison groups

IXE80Q2W v Placebo

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority ^[6]

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.4

Confidence interval

level

95%

sides

2-sided

lower limit

-2.2

upper limit

-0.59

Variability estimate

Standard error of the mean

Dispersion value

0.409

Notes
[6] - BASFI

ASAS Criteria

Statistical analysis description

Inflammation

Comparison groups

IXE80Q4W v Placebo

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority ^[7]

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2.17

Confidence interval

level

95%

sides

2-sided

lower limit

-3.05

upper limit

-1.28

Variability estimate

Standard error of the mean

Dispersion value

0.448

Notes
[7] - Inflammation

ASAS Criteria

Statistical analysis description

Inflammation

Comparison groups

IXE80Q2W v Placebo

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority ^[8]

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.8

Confidence interval

level

95%

sides

2-sided

lower limit

-2.66

upper limit

-0.95

Variability estimate

Standard error of the mean

Dispersion value

0.433

Notes
[8] - Inflammation

Secondary: Percentage of Participants Achieving Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI50) Response

Top of page

End point title

Percentage of Participants Achieving Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI50) Response

End point description

The BASDAI is a participant-reported assessment consisting of 6 questions that relate to 5 major symptoms relevant to radiographic axial spondyloarthritis (rad-axSpA): 1) Fatigue, 2) Spinal pain, 3) Peripheral arthritis, 4) Enthesitis, 5) Intensity, and 6) Duration of morning stiffness. Participants need to score each item with a score from 0 to 10 (NRS). Total score is obtained from the average of symptom scores ranging 0 (no problem) to 10 (worst problem), with a higher score indicating more severe AS symptom. BASDAI50 represents an improvement of ≥50% of the BASDAI score from baseline. APD: Participants who achieved a state of sustained remission and were randomized to 40-week double-blind placebo controlled RWR period (Group B). Missing data was imputed using the nonresponder imputation (NRI) method.

End point type

Secondary

End point timeframe

Week 64

End point values	Placebo	IXE80Q4W	IXE80Q2W
Number of subjects analysed	53	48	54
Units: Percentage of participants
number (not applicable)	45.3	81.3	75.9

BASDAI50

Comparison groups

IXE80Q4W v Placebo

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

5.34

Confidence interval

level

95%

sides

2-sided

lower limit

2.13

upper limit

13.35

BASDAI50

Comparison groups

IXE80Q2W v Placebo

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.07

Confidence interval

level

95%

sides

2-sided

lower limit

1.75

upper limit

9.45

Secondary: Change from Baseline in the Measure of High Sensitivity C-Reactive Protein (CRP)

Top of page

End point title

Change from Baseline in the Measure of High Sensitivity C-Reactive Protein (CRP)

End point description

High sensitivity CRP is the measure of acute phase reactant. It was measured with a high sensitivity assay at the central laboratory to help assess the effect of ixekizumab on disease activity. High sensitivity CRP is a sensitive laboratory assay for serum levels of C-Reactive Protein, which is a biomarker of inflammation. LS mean was determined by ANCOVA with treatment, geographic region, originating study, baseline value and Week 24 value as fixed factors. APD: Participants who achieved a state of sustained remission and were randomized to 40-week double-blind placebo controlled RWR period (Group B). Missing data was imputed using the modified baseline observation carried forward (mBOCF) method.

End point type

Secondary

End point timeframe

Baseline, Week 64

End point values	Placebo	IXE80Q4W	IXE80Q2W
Number of subjects analysed	53	48	54
Units: milligram per liter (mg/L)
least squares mean (standard error)	-5.094 ( 1.3696 )	-12.952 ( 1.4666 )	-11.074 ( 1.3861 )

High Sensitivity C-Reactive Protein (CRP)

Comparison groups

IXE80Q4W v Placebo

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-7.858

Confidence interval

level

95%

sides

2-sided

lower limit

-11.729

upper limit

-3.987

Variability estimate

Standard error of the mean

Dispersion value

1.9586

High Sensitivity C-Reactive Protein (CRP)

Comparison groups

IXE80Q2W v Placebo

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-5.979

Confidence interval

level

95%

sides

2-sided

lower limit

-9.655

upper limit

-2.304

Variability estimate

Standard error of the mean

Dispersion value

1.86

Secondary: Change from Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI)

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End point title

Change from Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI)

End point description

BASMI is a combined index comprising of the following 5 clinical measurements of spinal mobility in patients with radiographic axial spondyloarthritis (rad-axSpA). 1) Lateral Spinal Flexion 2) Tragus-to-wall distance 3) Lumbar Flexion (modified Schober) 4) Maximal intermalleolar distance and 5) Cervical rotation. The BASMI linear result is the average of the 5 assessments and ranges from 0 to 10. The higher the BASMI score the more severe the patient's limitation of movement due to their AS. LS mean was determined by ANCOVA with treatment, geographic region, originating study, baseline value and Week 24 value as fixed factors. APD: Participants who achieved a state of sustained remission and were randomized to 40-week double-blind placebo controlled RWR period (Group B). Missing data was imputed using the modified baseline observation carried forward (mBOCF) method.

End point type

Secondary

End point timeframe

Baseline, Week 64

End point values	Placebo	IXE80Q4W	IXE80Q2W
Number of subjects analysed	53	48	54
Units: Units on a scale
least squares mean (standard error)	-0.50 ( 0.073 )	-0.69 ( 0.080 )	-0.73 ( 0.075 )

BASMI

Comparison groups

IXE80Q4W v Placebo

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.062

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

0.01

Variability estimate

Standard error of the mean

Dispersion value

0.104

BASMI

Comparison groups

IXE80Q2W v Placebo

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.018

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.24

Confidence interval

level

95%

sides

2-sided

lower limit

-0.43

upper limit

-0.04

Variability estimate

Standard error of the mean

Dispersion value

0.099

Secondary: Change from Baseline in Chest Expansion in Centimeters

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End point title

Change from Baseline in Chest Expansion in Centimeters

End point description

Chest expansion is the difference, in centimeter (cm), between the circumference of the chest in maximal inspiration and maximal expiration. While patients have their hands resting on or behind the head, the assessor will measure the chest encircled length by centimeter (cm) at the fourth intercostal level anteriorly. Two tries were recorded. The better measurement (larger difference) of 2 tries (in centimeters) was used for analyses. LS mean was determined by ANCOVA with treatment, geographic region, originating study, baseline value and Week 24 value as fixed factors. APD: Participants who achieved a state of sustained remission and were randomized to 40-week double-blind placebo controlled RWR period (Group B). Missing data was imputed using the modified baseline observation carried forward (mBOCF) method.

End point type

Secondary

End point timeframe

Baseline, Week 64

End point values	Placebo	IXE80Q4W	IXE80Q2W
Number of subjects analysed	53	48	54
Units: centimeter (cm)
least squares mean (standard error)	0.67 ( 0.236 )	0.77 ( 0.256 )	0.53 ( 0.243 )

Chest Expansion in Centimeters

Comparison groups

IXE80Q4W v Placebo

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.757

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.56

upper limit

0.77

Variability estimate

Standard error of the mean

Dispersion value

0.335

Chest Expansion in Centimeters

Comparison groups

IXE80Q2W v Placebo

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.67

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.14

Confidence interval

level

95%

sides

2-sided

lower limit

-0.77

upper limit

0.5

Variability estimate

Standard error of the mean

Dispersion value

0.322

Secondary: Change from Baseline in Occiput to Wall Distance

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End point title

Change from Baseline in Occiput to Wall Distance

End point description

The participant is to make a maximum effort to touch the head against the wall when standing with heels and back against the wall (occiput). Then the distance from occiput to wall is measured. Two tries will be recorded. The better (smaller) measurement of 2 tries (in centimeters) will be used for analyses. LS mean was determined by ANCOVA with treatment, geographic region, originating study, baseline value and Week 24 value as fixed factors. APD: Participants who achieved a state of sustained remission and were randomized to 40-week double-blind placebo controlled RWR period (Group B). Missing data was imputed using the modified baseline observation carried forward (mBOCF) method.

End point type

Secondary

End point timeframe

Baseline, Week 64

End point values	Placebo	IXE80Q4W	IXE80Q2W
Number of subjects analysed	53	48	54
Units: cm
least squares mean (standard error)	-0.38 ( 0.235 )	-0.78 ( 0.260 )	-0.66 ( 0.239 )

Occiput to Wall Distance

Comparison groups

IXE80Q4W v Placebo

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.236

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.07

upper limit

0.27

Variability estimate

Standard error of the mean

Dispersion value

0.338

Occiput to Wall Distance

Comparison groups

IXE80Q2W v Placebo

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.373

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.28

Confidence interval

level

95%

sides

2-sided

lower limit

-0.92

upper limit

0.35

Variability estimate

Standard error of the mean

Dispersion value

0.319

Secondary: Change from Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES)

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End point title

Change from Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES)

End point description

The MASES is an index used to measure the severity of enthesitis. The MASES assesses 13 sites for enthesitis using a score of "0" for no activity or "1" for activity. Sites assessed include costochondral 1 (right/left), costochondral 7 (right/left), spinal iliaca anterior superior (right/left), crista iliaca (right/left), spina iliaca posterior (right/left), processus spinosus L5, and Achilles tendon proximal insertion (right/left). The MASES is the sum of all site scores (range 0 to 13); higher scores indicate more severe enthesitis. LS mean was determined by ANCOVA with treatment, geographic region, originating study, baseline value and Week 24 value as fixed factors. APD: Participants who achieved a state of sustained remission and were randomized to 40-week double-blind placebo controlled RWR period (Group B), and with Baseline MASES score >0. Missing data was imputed using the modified baseline observation carried forward (mBOCF) method.

End point type

Secondary

End point timeframe

Baseline, Week 64

End point values	Placebo	IXE80Q4W	IXE80Q2W
Number of subjects analysed	35	29	36
Units: Units on a scale
least squares mean (standard error)	-3.48 ( 0.302 )	-3.55 ( 0.352 )	-3.62 ( 0.315 )

MASES

Comparison groups

IXE80Q4W v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.885

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.07

Confidence interval

level

95%

sides

2-sided

lower limit

-0.98

upper limit

0.85

Variability estimate

Standard error of the mean

Dispersion value

0.459

MASES

Comparison groups

IXE80Q2W v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.735

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.14

Confidence interval

level

95%

sides

2-sided

lower limit

-0.95

upper limit

0.68

Variability estimate

Standard error of the mean

Dispersion value

0.41

Secondary: Change from Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Score

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End point title

Change from Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Score

End point description

The SPARCC enthesitis is an index used to measure the severity of enthesitis. The SPARCC assesses 16 sites for enthesitis using a score of "0" for no activity or "1" for activity. Sites assessed include Medial epicondyle (left/right [L/R]), Lateral epicondyle (L/R), Supraspinatus insertion into greater tuberosity of humerus (L/R), Greater trochanter (L/R), Quadriceps insertion into superior border of patella (L/R), Patellar ligament insertion into inferior pole of patella or tibial tubercle (L/R), Achilles tendon insertion into calcaneum (L/R), and Plantar fascia insertion into calcaneum (L/R). The SPARCC is the sum of all site scores (range 0 to 16). Higher scores indicate more severe enthesitis. LS mean was determined by ANCOVA with treatment, geographic region, originating study, baseline value and Week 24 value as fixed factors. APD: Participants who achieved a state of sustained remission and were randomized to 40-week double-blind placebo controlled RWR period (Group B).

End point type

Secondary

End point timeframe

Baseline, Week 64

End point values	Placebo	IXE80Q4W	IXE80Q2W
Number of subjects analysed	30	22	30
Units: Units on a scale
least squares mean (standard error)	-2.71 ( 0.335 )	-3.23 ( 0.388 )	-3.34 ( 0.338 )

SPARCC Enthesitis Score

Comparison groups

IXE80Q4W v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.294

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.53

Confidence interval

level

95%

sides

2-sided

lower limit

-1.53

upper limit

0.47

Variability estimate

Standard error of the mean

Dispersion value

0.501

SPARCC Enthesitis Score

Comparison groups

IXE80Q2W v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.164

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.64

Confidence interval

level

95%

sides

2-sided

lower limit

-1.54

upper limit

0.27

Variability estimate

Standard error of the mean

Dispersion value

0.453

Secondary: Change from Baseline in Severity of Peripheral Arthritis by Tender Joint Count (TJC) Score of 46 Joints

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End point title

Change from Baseline in Severity of Peripheral Arthritis by Tender Joint Count (TJC) Score of 46 Joints

End point description

The number of tender and painful joints was determined by examination of 46 joints (23 joints on each side of the body). The 46 joints were assessed and classified as tender or not tender. Sum of all joints checked to be tender/painful divided by number of evaluable joints which was multiplied by 46 to obtain TJC score. The scores ranges from 0 (no tender/painful joints) to 46 (all joints tender/painful). LS mean was determined by ANCOVA with treatment, geographic region, originating study, baseline value and Week 24 value as fixed factors. APD: Participants who achieved a state of sustained remission and were randomized to 40-week double-blind placebo controlled RWR period (Group B), and with baseline TJC >0. Missing data was imputed using the modified baseline observation carried forward (mBOCF) method.

End point type

Secondary

End point timeframe

Baseline, Week 64

End point values	Placebo	IXE80Q4W	IXE80Q2W
Number of subjects analysed	23	27	33
Units: Units on a scale
least squares mean (standard error)	-4.0 ( 0.85 )	-6.1 ( 0.76 )	-5.3 ( 0.74 )

TJC Score

Comparison groups

IXE80Q4W v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.063

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2.1

Confidence interval

level

95%

sides

2-sided

lower limit

-4.3

upper limit

0.1

Variability estimate

Standard error of the mean

Dispersion value

1.1

TJC Score

Comparison groups

IXE80Q2W v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.211

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.3

Confidence interval

level

95%

sides

2-sided

lower limit

-3.3

upper limit

0.7

Variability estimate

Standard error of the mean

Dispersion value

1.02

Secondary: Change from Baseline in Severity of Peripheral Arthritis by Swollen Joint Count (SJC) Score of 44 Joints

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End point title

Change from Baseline in Severity of Peripheral Arthritis by Swollen Joint Count (SJC) Score of 44 Joints

End point description

The number of swollen joints was determined by examination of 44 joints (22 joints on each side of the body). The 44 joints were assessed and classified as swollen or not swollen. Sum of all joints checked to be swollen divided by number of evaluable joints which was multiplied by 44 to obtain SJC score. The SJC score ranges from 0 (no swollen joints) to 44 (all joints swollen). LS mean was determined by ANCOVA with treatment, geographic region, originating study, baseline value and Week 24 value as fixed factors. APD: Participants who achieved a state of sustained remission and were randomized to 40-week double-blind placebo controlled RWR period (Group B), and with baseline SJC >0. Missing data was imputed using the modified baseline observation carried forward (mBOCF) method.

End point type

Secondary

End point timeframe

Baseline, Week 64

End point values	Placebo	IXE80Q4W	IXE80Q2W
Number of subjects analysed	15	16	21
Units: Units on a scale
least squares mean (standard error)	-2.7 ( 0.73 )	-3.6 ( 0.67 )	-3.9 ( 0.59 )

SJC Score

Comparison groups

IXE80Q4W v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.334

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-2.7

upper limit

0.9

Variability estimate

Standard error of the mean

Dispersion value

0.9

SJC Score

Comparison groups

IXE80Q2W v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.168

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.2

Confidence interval

level

95%

sides

2-sided

lower limit

-3

upper limit

0.5

Variability estimate

Standard error of the mean

Dispersion value

0.88

Secondary: Percentage of Participants with Anterior Uveitis or Uveitis Flares

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End point title

Percentage of Participants with Anterior Uveitis or Uveitis Flares

End point description

Anterior uveitis is an inflammation of the middle layer of the eye, which includes the iris (colored part of the eye) and the adjacent tissue, known as the ciliary body. APD: Participants who achieved a state of sustained remission and were randomized to 40-week double-blind placebo controlled RWR period (Group B), and regardless of history of anterior uveitis.

End point type

Secondary

End point timeframe

Week 64

End point values	Placebo	IXE80Q4W	IXE80Q2W
Number of subjects analysed	53	48	54
Units: Percentage of Participants
number (not applicable)	5.7	4.2	5.6

No statistical analyses for this end point

Secondary: Change from Baseline in the Fatigue Numeric Rating Scale (NRS) Score

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End point title

Change from Baseline in the Fatigue Numeric Rating Scale (NRS) Score

End point description

The fatigue severity NRS is a participant administered single-item 11-point horizontal scale anchored at 0 and 10, with 0 representing "no fatigue" and 10 representing "as bad as you can imagine". Participants rate their fatigue (feeling tired or worn out) by circling the 1 number that describes their worst level of fatigue during the previous 24 hours. LS mean was determined by ANCOVA with treatment, geographic region, originating study, baseline value and Week 24 value as fixed factors. APD: Participants who achieved a state of sustained remission and were randomized to 40-week double-blind placebo controlled RWR period (Group B). Missing data was imputed using the modified baseline observation carried forward (mBOCF) method.

End point type

Secondary

End point timeframe

Baseline, Week 64

End point values	Placebo	IXE80Q4W	IXE80Q2W
Number of subjects analysed	53	48	54
Units: units on a scale
least squares mean (standard error)	-3.5 ( 0.28 )	-4.2 ( 0.31 )	-4.3 ( 0.29 )

NRS Score

Comparison groups

IXE80Q4W v Placebo

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.5

upper limit

0.1

Variability estimate

Standard error of the mean

Dispersion value

0.4

NRS Score

Comparison groups

IXE80Q2W v Placebo

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.047

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.5

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.38

Secondary: Change from Baseline on the Quick Inventory of Depressive Symptomatology Self-Report-16 (QIDS-SR16)

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End point title

Change from Baseline on the Quick Inventory of Depressive Symptomatology Self-Report-16 (QIDS-SR16)

End point description

The 16-item QIDS-SR16 version is a widely used validated scale designed to assess the severity of depressive symptoms. The participant was asked to rate the severity and frequency of specific symptoms present over the last 7 days. The QIDS-SR16 total scores range from 0 to 27, where higher scores indicate higher severity of symptoms. LS mean was determined by ANCOVA with treatment, geographic region, originating study, baseline value and Week 24 value as fixed factors. APD: Participants who achieved a state of sustained remission and were randomized to 40-week double-blind placebo controlled RWR period (Group B). Missing data was imputed using the modified baseline observation carried forward (mBOCF) method.

End point type

Secondary

End point timeframe

Baseline, Week 64

End point values	Placebo	IXE80Q4W	IXE80Q2W
Number of subjects analysed	53	48	54
Units: units on a scale
least squares mean (standard error)	-2.80 ( 0.342 )	-3.68 ( 0.362 )	-3.28 ( 0.344 )

QIDS-SR16

Comparison groups

IXE80Q4W v Placebo

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.068

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.88

Confidence interval

level

95%

sides

2-sided

lower limit

-1.83

upper limit

0.06

Variability estimate

Standard error of the mean

Dispersion value

0.479

QIDS-SR16

Comparison groups

IXE80Q2W v Placebo

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.307

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.48

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

0.44

Variability estimate

Standard error of the mean

Dispersion value

0.465

Secondary: Change from Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) Score

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End point title

Change from Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) Score

End point description

The SF-36 is a 36-item participant administered measure designed to be a short, multipurpose assessment of health in the areas of physical functioning, role - physical, role - emotional, bodily pain, vitality, social functioning, mental health, and general health. The 2 overarching domains of mental well- being and physical well-being are captured by the Mental Component Summary and Physical Component Summary scores. T-scores are used for analysis. The summary scores range from 0 to 100, with higher scores indicating better levels of function and/or better health. LS mean was determined by ANCOVA with treatment, geographic region, originating study, baseline value and Week 24 value as fixed factors. APD: Participants who achieved a state of sustained remission and were randomized to 40-week double-blind placebo controlled RWR period (Group B). Missing data was imputed using the modified baseline observation carried forward (mBOCF) method.

End point type

Secondary

End point timeframe

Baseline, Week 64

End point values	Placebo	IXE80Q4W	IXE80Q2W
Number of subjects analysed	53	48	54
Units: units on a scale
least squares mean (standard error)	10.6934 ( 1.0366 )	13.2954 ( 1.1210 )	13.1030 ( 1.0457 )

Physical Component Summary (PCS) Score

Comparison groups

IXE80Q4W v Placebo

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.079

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

2.6021

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3011

upper limit

5.5053

Variability estimate

Standard error of the mean

Dispersion value

1.4684

Physical Component Summary (PCS) Score

Comparison groups

IXE80Q2W v Placebo

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.087

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

2.4096

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3541

upper limit

5.1734

Variability estimate

Standard error of the mean

Dispersion value

1.3978

Secondary: Change from Baseline in SF-36 Mental Component Summary (MCS) Score

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End point title

Change from Baseline in SF-36 Mental Component Summary (MCS) Score

End point description

End point type

Secondary

End point timeframe

Baseline, Week 64

End point values	Placebo	IXE80Q4W	IXE80Q2W
Number of subjects analysed	53	48	54
Units: units on a scale
least squares mean (standard error)	2.3396 ( 0.8314 )	3.1766 ( 0.8968 )	4.6404 ( 0.8369 )

Mental Component Summary (MCS) Score

Comparison groups

IXE80Q4W v Placebo

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.477

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

0.837

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4864

upper limit

3.1605

Variability estimate

Standard error of the mean

Dispersion value

1.1752

Mental Component Summary (MCS) Score

Comparison groups

IXE80Q2W v Placebo

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.042

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

2.3009

Confidence interval

level

95%

sides

2-sided

lower limit

0.088

upper limit

4.5138

Variability estimate

Standard error of the mean

Dispersion value

1.1192

Secondary: Change from Baseline in ASAS Health Index (ASAS HI)

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End point title

Change from Baseline in ASAS Health Index (ASAS HI)

End point description

The ASAS Health Index (ASAS HI) is a disease specific health-index instrument designed to assess the impact of interventions for SpA, including axSpA. The 17 item instrument has scores ranging from 0 (good Health) to 17 (poor Health). Each item consists of 1 question that the patient needs to respond to with either "I agree" (score 1) or "I do not agree (score 0)." A score of "1" is given where the item is affirmed, indicating adverse health. All item scores are summed to give a total score or index. LS mean was determined by ANCOVA with treatment, geographic region, originating study, baseline value and Week 24 value as fixed factors. APD: Participants who achieved a state of sustained remission and were randomized to 40-week double-blind placebo controlled RWR period (Group B). Missing data was imputed using the modified baseline observation carried forward (mBOCF) method.

End point type

Secondary

End point timeframe

Baseline, Week 64

End point values	Placebo	IXE80Q4W	IXE80Q2W
Number of subjects analysed	53	48	54
Units: units on a scale
least squares mean (standard error)	-3.64 ( 0.370 )	-4.64 ( 0.393 )	-4.37 ( 0.368 )

ASAS HI

Comparison groups

IXE80Q4W v Placebo

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.058

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.99

Confidence interval

level

95%

sides

2-sided

lower limit

-2.02

upper limit

0.04

Variability estimate

Standard error of the mean

Dispersion value

0.52

ASAS HI

Comparison groups

IXE80Q2W v Placebo

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.147

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.72

Confidence interval

level

95%

sides

2-sided

lower limit

-1.71

upper limit

0.26

Variability estimate

Standard error of the mean

Dispersion value

0.497

Secondary: Change from Baseline in the European Quality of Life - 5 Dimensions 5 Level (EQ-5D-5L) UK population-based index score

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End point title

Change from Baseline in the European Quality of Life - 5 Dimensions 5 Level (EQ-5D-5L) UK population-based index score

End point description

The European Quality of Life - 5 Dimensions 5 Level (EQ-5D-5L) is a standardized measure of health status used to provide a simple, generic measure of health for clinical and economic appraisal. The EQ-5D-5L consists of 2 components: a descriptive system of the respondent’s health and a rating of his/her current health state using a 0- to 100-mm visual analog scale (VAS). The descriptive system comprises the following 5 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. LS mean was determined by ANCOVA with treatment, geographic region, originating study, baseline value and Week 24 value as fixed factors. APD: Participants who achieved a state of sustained remission and were randomized to 40-week double-blind placebo controlled RWR period (Group B). Missing data was imputed using the mBOCF method.

End point type

Secondary

End point timeframe

Baseline, Week 64

End point values	Placebo	IXE80Q4W	IXE80Q2W
Number of subjects analysed	53	48	54
Units: units on a scale
least squares mean (standard error)	0.2459 ( 0.0237 )	0.2877 ( 0.0252 )	0.2847 ( 0.0235 )

EQ-5D-5L UK Population-based Index Score

Comparison groups

Placebo v IXE80Q4W

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.213

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

0.0418

Confidence interval

level

95%

sides

2-sided

lower limit

-0.0329

upper limit

0.1164

Variability estimate

Standard error of the mean

Dispersion value

0.0334

EQ-5D-5L UK Population-based Index Score

Comparison groups

Placebo v IXE80Q2W

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.225

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

0.0388

Confidence interval

level

95%

sides

2-sided

lower limit

-0.0324

upper limit

0.1101

Variability estimate

Standard error of the mean

Dispersion value

0.0319

Secondary: Change from Baseline in the Work Productivity Activity Impairment Spondyloarthritis (WPAI-SpA) Scores

Top of page

End point title

Change from Baseline in the Work Productivity Activity Impairment Spondyloarthritis (WPAI-SpA) Scores

End point description

The WPAI-SpA consists of 6 questions to determine employment status, hours missed from work because of SpA, hours missed from work for other reasons, hours actually worked, the degree to which SpA affected work productivity while at work, and the degree to which SpA affected activities outside of work. The WPAI-SpA has been validated in the rad-axSpA patient population. Four scores are derived: percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment score that combines absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. The computed percentage range for each sub-scale was from 0-100, with higher scores indicating greater impairment and less productivity. LS mean was determined by ANCOVA. APD: Participants who achieved a state of sustained remission and were randomized to 40-week double-blind placebo controlled RWR period (Group B). Missing data was imputed using MBOCF.

End point type

Secondary

End point timeframe

Baseline, Week 64

End point values	Placebo	IXE80Q4W	IXE80Q2W
Number of subjects analysed	53	48	54
Units: units on a scale
least squares mean (standard error)
Overall Work Impairment Score	-28.73 ( 3.677 )	-40.94 ( 3.752 )	-36.53 ( 3.221 )
Percentage of Activity Impairment	-32.96 ( 3.099 )	-43.58 ( 3.329 )	-40.10 ( 3.115 )

WPAI-SpA Scores

Statistical analysis description

Overall Work Impairment Score

Comparison groups

IXE80Q4W v Placebo

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority ^[9]

P-value

= 0.016

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-12.21

Confidence interval

level

95%

sides

2-sided

lower limit

-22.04

upper limit

-2.38

Variability estimate

Standard error of the mean

Dispersion value

4.939

Notes
[9] - Overall Work Impairment Score

WPAI-SpA Scores

Statistical analysis description

Overall Work Impairment Score

Comparison groups

IXE80Q2W v Placebo

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority ^[10]

P-value

= 0.092

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-7.8

Confidence interval

level

95%

sides

2-sided

lower limit

-16.91

upper limit

1.31

Variability estimate

Standard error of the mean

Dispersion value

4.578

Notes
[10] - Overall Work Impairment Score

WPAI-SpA Scores

Statistical analysis description

Percentage of Activity Impairment

Comparison groups

IXE80Q4W v Placebo

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority ^[11]

P-value

= 0.017

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-10.62

Confidence interval

level

95%

sides

2-sided

lower limit

-19.28

upper limit

-1.95

Variability estimate

Standard error of the mean

Dispersion value

4.383

Notes
[11] - Percentage of Activity Impairment

WPAI-SpA Scores

Statistical analysis description

Percentage of Activity Impairment

Comparison groups

IXE80Q2W v Placebo

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority ^[12]

P-value

= 0.091

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-7.14

Confidence interval

level

95%

sides

2-sided

lower limit

-15.44

upper limit

1.16

Variability estimate

Standard error of the mean

Dispersion value

4.199

Notes
[12] - Percentage of Activity Impairment

Secondary: Change from Baseline in the Jenkins Sleep Evaluation Questionnaire (JSEQ)

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End point title

Change from Baseline in the Jenkins Sleep Evaluation Questionnaire (JSEQ)

End point description

JSEQ is a 4 item scale designed to estimate sleep problems in clinical research. The JSEQ assesses the frequency of sleep disturbance in 4 categories: 1) trouble falling asleep, 2) waking up several times during the night, 3) having trouble staying asleep (including waking up far too early), and 4) waking up after the usual amount of sleep feeling tired and worn out. Patients report the numbers of days they experience each of these problems in the past month on a 6 point Likert Scale ranging from 0 = "no days" to 5 = "22-30 days. The total JSEQ score ranges from 0 to 20, with higher scores indicating greater sleep disturbance. LS mean was determined by ANCOVA with treatment, geographic region, originating study, baseline value and Week 24 value as fixed factors. APD: Participants who achieved a state of sustained remission and were randomized to 40-week double-blind placebo controlled RWR period (Group B). Missing data was imputed using mBOCF method.

End point type

Secondary

End point timeframe

Baseline, Week 64

End point values	Placebo	IXE80Q4W	IXE80Q2W
Number of subjects analysed	53	48	54
Units: units on a scale
least squares mean (standard error)	-3.6 ( 0.47 )	-4.0 ( 0.50 )	-3.8 ( 0.47 )

JSEQ

Comparison groups

IXE80Q4W v Placebo

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.531

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7

upper limit

0.9

Variability estimate

Standard error of the mean

Dispersion value

0.66

JSEQ

Comparison groups

IXE80Q2W v Placebo

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.743

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.62

Secondary: Percentage of Participants with No New Syndesmophyte Formation

Top of page

End point title

Percentage of Participants with No New Syndesmophyte Formation

End point description

Percentage of participants with no new syndesmophyte formation was measured using the average score of 2 selected readers of 3 readers. APD: Ixekizumab structure population who have been treated with Ixekizumab for at least 24 months

End point type

Secondary

End point timeframe

Week 56

End point values	IXE80Q4W	IXE80Q2W
Number of subjects analysed	115	115
Units: Percentage of participants
number (not applicable)	80.9	87.8

No statistical analyses for this end point

Secondary: Percentage of Participants with Anti-Ixekizumab Antibodies

Top of page

End point title

Percentage of Participants with Anti-Ixekizumab Antibodies

End point description

A treatment emergent - antidrug antibody (TE-ADA) positive patient is defined as: a) a patient with a >= 4-fold increase over a positive baseline antibody titer; or b) for a negative baseline titer, a patient with an increase from the baseline to a level of >= 1:10. Percentage was calculated based on the number of evaluable participants and was calculated by number of participants with treatment-emergent positive anti-ixekizumab antibodies / number of evaluable participants * 100%. APD: All randomized participants from Group B, who received at least one dose of study drug.

End point type

Secondary

End point timeframe

Baseline, Week 64

End point values	Placebo	IXE80Q4W	IXE80Q2W
Number of subjects analysed	45	43	51
Units: Percentage of participants
number (not applicable)	4.7	2.0	20.0

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Baseline, up to 128 weeks

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.0

Reporting group title

IXE80Q2W-lead-in period

Reporting group description

Reporting group title

IXE80Q4W-lead-in period

Reporting group description

Reporting group title

IXE80Q4W-randomized withdrawal extension period

Reporting group description

Reporting group title

IXE80Q2W-randomized withdrawal extension period

Reporting group description

Reporting group title

IXE80Q4W-group A extension period

Reporting group description

Reporting group title

IXE80Q2W-group A extension period

Reporting group description

Reporting group title

IXE80Q2W/IXE80Q2W-retreatment extension period

Reporting group description

Reporting group title

IXE80Q4W/IXE80Q4W-retreatment extension period

Reporting group description

Reporting group title

PBO-randomized withdrawal extension period

Reporting group description

Reporting group title

IXE80Q4W-group A long-term extension period

Reporting group description

Reporting group title

PBO/IXE80Q2W-retreatment extension period

Reporting group description

Reporting group title

IXE80Q2W-group A long-term extension period

Reporting group description

Reporting group title

PBO/IXE80Q4W-retreatment extension period

Reporting group description

Reporting group title

IXE80Q2W-randomized withdrawal long-term extension period

Reporting group description

Reporting group title

IXE80Q4W-randomized withdrawal long-term extension period

Reporting group description

Reporting group title

PBO-randomized withdrawal long-term extension period

Reporting group description

Reporting group title

IXE80Q4W/IXE80Q4W-retreatment long-term extension period

Reporting group description

Reporting group title

PBO/IXE80Q2W-retreatment long-term extension period

Reporting group description

Reporting group title

PBO/IXE80Q4W-retreatment long-term extension period

Reporting group description

Reporting group title

IXE80Q2W/IXE80Q2W-retreatment long-term extension period

Reporting group description

Reporting group title

PBO-randomized withdrawal escalation period

Reporting group description

Reporting group title

IXE80Q4W-randomized withdrawal escalation period

Reporting group description

Reporting group title

IXE80Q4W-group A escalation period

Reporting group description

Reporting group title

PBO-follow-up period

Reporting group description

Reporting group title

IXE80Q4W-follow-up period

Reporting group description

Reporting group title

IXE80Q2W-follow-up period

Reporting group description

IXE80Q2W-lead-in period

IXE80Q4W-lead-in period

IXE80Q4W-randomized withdrawal extension period

IXE80Q2W-randomized withdrawal extension period

IXE80Q4W-group A extension period

IXE80Q2W-group A extension period

IXE80Q2W/IXE80Q2W-retreatment extension period

IXE80Q4W/IXE80Q4W-retreatment extension period

PBO-randomized withdrawal extension period

IXE80Q4W-group A long-term extension period

PBO/IXE80Q2W-retreatment extension period

IXE80Q2W-group A long-term extension period

PBO/IXE80Q4W-retreatment extension period

IXE80Q2W-randomized withdrawal long-term extension period

IXE80Q4W-randomized withdrawal long-term extension period

PBO-randomized withdrawal long-term extension period

IXE80Q4W/IXE80Q4W-retreatment long-term extension period

PBO/IXE80Q2W-retreatment long-term extension period

PBO/IXE80Q4W-retreatment long-term extension period

IXE80Q2W/IXE80Q2W-retreatment long-term extension period

PBO-randomized withdrawal escalation period

IXE80Q4W-randomized withdrawal escalation period

IXE80Q4W-group A escalation period

PBO-follow-up period

IXE80Q4W-follow-up period

IXE80Q2W-follow-up period

Total subjects affected by serious adverse events

subjects affected / exposed

12 / 423 (2.84%)

10 / 348 (2.87%)

2 / 47 (4.26%)

2 / 54 (3.70%)

12 / 255 (4.71%)

11 / 318 (3.46%)

1 / 6 (16.67%)

0 / 5 (0.00%)

1 / 53 (1.89%)

3 / 177 (1.69%)

0 / 9 (0.00%)

15 / 306 (4.90%)

0 / 10 (0.00%)

1 / 45 (2.22%)

1 / 42 (2.38%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 77 (1.30%)

0 / 25 (0.00%)

3 / 223 (1.35%)

2 / 453 (0.44%)

number of deaths (all causes)

number of deaths resulting from adverse events

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

abdominal neoplasm

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

1 / 306 (0.33%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

adenocarcinoma

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

1 / 306 (0.33%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

anal cancer

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

1 / 423 (0.24%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

benign lung neoplasm

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

1 / 318 (0.31%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

breast cancer

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

1 / 423 (0.24%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

chronic lymphocytic leukaemia

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

1 / 318 (0.31%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

ovarian cancer

alternative dictionary used: MedDRA 24.0

subjects affected / exposed ^[1]

1 / 130 (0.77%)

0 / 92 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 68 (0.00%)

0 / 95 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

0 / 15 (0.00%)

0 / 47 (0.00%)

0 / 2 (0.00%)

0 / 91 (0.00%)

0 / 2 (0.00%)

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 8 (0.00%)

0 / 57 (0.00%)

0 / 136 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ovarian germ cell teratoma benign

alternative dictionary used: MedDRA 24.0

subjects affected / exposed ^[2]

0 / 130 (0.00%)

0 / 92 (0.00%)

1 / 10 (10.00%)

0 / 14 (0.00%)

0 / 68 (0.00%)

0 / 95 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

0 / 15 (0.00%)

0 / 47 (0.00%)

0 / 2 (0.00%)

0 / 91 (0.00%)

0 / 2 (0.00%)

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 8 (0.00%)

0 / 57 (0.00%)

0 / 136 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

papillary thyroid cancer

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

1 / 255 (0.39%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

venous thrombosis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

1 / 306 (0.33%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

venous thrombosis limb

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

1 / 255 (0.39%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General disorders and administration site conditions

death

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

1 / 255 (0.39%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

soft tissue inflammation

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 53 (1.89%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Reproductive system and breast disorders

dysmenorrhoea

alternative dictionary used: MedDRA 24.0

subjects affected / exposed ^[3]

0 / 130 (0.00%)

0 / 92 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 68 (0.00%)

0 / 95 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

0 / 15 (0.00%)

0 / 47 (0.00%)

0 / 2 (0.00%)

1 / 91 (1.10%)

0 / 2 (0.00%)

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 8 (0.00%)

0 / 57 (0.00%)

0 / 136 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

haemothorax

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

1 / 318 (0.31%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Psychiatric disorders

depression

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

1 / 423 (0.24%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

major depression

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

1 / 318 (0.31%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

suicidal ideation

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

1 / 318 (0.31%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Investigations

blood creatine phosphokinase increased

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

1 / 348 (0.29%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

clavicle fracture

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

1 / 318 (0.31%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

comminuted fracture

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

1 / 177 (0.56%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

compression fracture

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

1 / 47 (2.13%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

concussion

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

1 / 318 (0.31%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

contusion

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

1 / 318 (0.31%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

femur fracture

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

1 / 348 (0.29%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ilium fracture

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

1 / 318 (0.31%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ligament sprain

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

1 / 255 (0.39%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

limb injury

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

1 / 318 (0.31%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

lumbar vertebral fracture

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

1 / 318 (0.31%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

meniscus injury

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

1 / 348 (0.29%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pneumothorax traumatic

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

1 / 318 (0.31%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

rib fracture

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

1 / 318 (0.31%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

spinal column injury

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

1 / 348 (0.29%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

synovial rupture

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

1 / 318 (0.31%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

acute myocardial infarction

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

1 / 306 (0.33%)

0 / 10 (0.00%)

1 / 45 (2.22%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cardiac failure acute

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

1 / 255 (0.39%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

coronary artery stenosis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

1 / 177 (0.56%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

myocardial infarction

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

1 / 255 (0.39%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

1 / 177 (0.56%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 77 (1.30%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

myocardial ischaemia

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

1 / 306 (0.33%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

1 / 453 (0.22%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Nervous system disorders

cerebral venous sinus thrombosis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

1 / 306 (0.33%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

hypoglycaemic unconsciousness

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

1 / 423 (0.24%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

myelopathy

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

1 / 54 (1.85%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

radiculopathy

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

1 / 318 (0.31%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

neutropenia

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

1 / 223 (0.45%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Eye disorders

iridocyclitis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

1 / 255 (0.39%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

colitis ulcerative

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

2 / 423 (0.47%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

2 / 255 (0.78%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

1 / 2

0 / 0

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

crohn's disease

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

1 / 223 (0.45%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

inguinal hernia

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

1 / 423 (0.24%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

1 / 177 (0.56%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

strangulated umbilical hernia

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

1 / 318 (0.31%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

cholecystitis acute

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

1 / 423 (0.24%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Skin and subcutaneous tissue disorders

subcutaneous emphysema

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

1 / 318 (0.31%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

urticaria

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

1 / 318 (0.31%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

calculus urinary

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

1 / 348 (0.29%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

nephrolithiasis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

1 / 306 (0.33%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

renal colic

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

1 / 306 (0.33%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ureterolithiasis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

1 / 255 (0.39%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

1 / 306 (0.33%)

0 / 10 (0.00%)

0 / 45 (0.00%)

1 / 42 (2.38%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

urinary incontinence

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

1 / 453 (0.22%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

arthritis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

1 / 318 (0.31%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

axial spondyloarthritis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

1 / 306 (0.33%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

back pain

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

1 / 423 (0.24%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

1 / 306 (0.33%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

osteoarthritis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

1 / 423 (0.24%)

2 / 348 (0.57%)

0 / 47 (0.00%)

0 / 54 (0.00%)

2 / 255 (0.78%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

1 / 306 (0.33%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 2

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pseudarthrosis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

1 / 223 (0.45%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

spinal ligament ossification

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

1 / 423 (0.24%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

temporomandibular joint syndrome

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

1 / 423 (0.24%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

tenosynovitis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

1 / 423 (0.24%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

appendicitis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

3 / 306 (0.98%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

covid-19

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

1 / 223 (0.45%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

cellulitis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

1 / 348 (0.29%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

chronic tonsillitis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

1 / 54 (1.85%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

clostridium difficile colitis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

1 / 348 (0.29%)

0 / 47 (0.00%)

1 / 54 (1.85%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

influenza

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

1 / 6 (16.67%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

orchitis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed ^[4]

0 / 293 (0.00%)

1 / 256 (0.39%)

0 / 37 (0.00%)

0 / 40 (0.00%)

0 / 187 (0.00%)

0 / 223 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 130 (0.00%)

0 / 7 (0.00%)

0 / 215 (0.00%)

0 / 8 (0.00%)

0 / 34 (0.00%)

0 / 33 (0.00%)

0 / 21 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 56 (0.00%)

0 / 17 (0.00%)

0 / 166 (0.00%)

0 / 317 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

respiratory tract infection viral

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

1 / 255 (0.39%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

sepsis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

1 / 255 (0.39%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

urinary tract infection

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

1 / 348 (0.29%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Metabolism and nutrition disorders

hyperglycaemia

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

1 / 348 (0.29%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

0 / 318 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

hyperkalaemia

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 423 (0.00%)

0 / 348 (0.00%)

0 / 47 (0.00%)

0 / 54 (0.00%)

0 / 255 (0.00%)

1 / 318 (0.31%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 53 (0.00%)

0 / 177 (0.00%)

0 / 9 (0.00%)

0 / 306 (0.00%)

0 / 10 (0.00%)

0 / 45 (0.00%)

0 / 42 (0.00%)

0 / 30 (0.00%)

0 / 4 (0.00%)

0 / 11 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 77 (0.00%)

0 / 25 (0.00%)

0 / 223 (0.00%)

0 / 453 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.
[2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.
[3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.
[4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.

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

Non-serious adverse events	IXE80Q2W-lead-in period	IXE80Q4W-lead-in period	IXE80Q4W-randomized withdrawal extension period	IXE80Q2W-randomized withdrawal extension period	IXE80Q4W-group A extension period	IXE80Q2W-group A extension period	IXE80Q2W/IXE80Q2W-retreatment extension period	IXE80Q4W/IXE80Q4W-retreatment extension period	PBO-randomized withdrawal extension period	IXE80Q4W-group A long-term extension period	PBO/IXE80Q2W-retreatment extension period	IXE80Q2W-group A long-term extension period	PBO/IXE80Q4W-retreatment extension period	IXE80Q2W-randomized withdrawal long-term extension period	IXE80Q4W-randomized withdrawal long-term extension period	PBO-randomized withdrawal long-term extension period	IXE80Q4W/IXE80Q4W-retreatment long-term extension period	PBO/IXE80Q2W-retreatment long-term extension period	PBO/IXE80Q4W-retreatment long-term extension period	IXE80Q2W/IXE80Q2W-retreatment long-term extension period	PBO-randomized withdrawal escalation period	IXE80Q4W-randomized withdrawal escalation period	IXE80Q4W-group A escalation period	PBO-follow-up period	IXE80Q4W-follow-up period	IXE80Q2W-follow-up period
Total subjects affected by non serious adverse events
subjects affected / exposed	108 / 423 (25.53%)	79 / 348 (22.70%)	8 / 47 (17.02%)	17 / 54 (31.48%)	62 / 255 (24.31%)	82 / 318 (25.79%)	0 / 6 (0.00%)	4 / 5 (80.00%)	16 / 53 (30.19%)	37 / 177 (20.90%)	2 / 9 (22.22%)	52 / 306 (16.99%)	1 / 10 (10.00%)	8 / 45 (17.78%)	6 / 42 (14.29%)	9 / 30 (30.00%)	3 / 4 (75.00%)	6 / 11 (54.55%)	5 / 15 (33.33%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 5 (40.00%)	6 / 77 (7.79%)	0 / 25 (0.00%)	14 / 223 (6.28%)	27 / 453 (5.96%)
Surgical and medical procedures
keratomileusis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 423 (0.00%)	0 / 348 (0.00%)	0 / 47 (0.00%)	0 / 54 (0.00%)	0 / 255 (0.00%)	0 / 318 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 53 (0.00%)	0 / 177 (0.00%)	0 / 9 (0.00%)	0 / 306 (0.00%)	0 / 10 (0.00%)	0 / 45 (0.00%)	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 77 (0.00%)	0 / 25 (0.00%)	0 / 223 (0.00%)	0 / 453 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
General disorders and administration site conditions
fatigue
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	3 / 423 (0.71%)	0 / 348 (0.00%)	0 / 47 (0.00%)	1 / 54 (1.85%)	1 / 255 (0.39%)	1 / 318 (0.31%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 53 (0.00%)	0 / 177 (0.00%)	0 / 9 (0.00%)	2 / 306 (0.65%)	0 / 10 (0.00%)	0 / 45 (0.00%)	0 / 42 (0.00%)	1 / 30 (3.33%)	0 / 4 (0.00%)	1 / 11 (9.09%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 77 (0.00%)	0 / 25 (0.00%)	0 / 223 (0.00%)	0 / 453 (0.00%)
occurrences all number	3	0	0	1	1	1	0	0	0	0	0	2	0	0	0	1	0	1	0	0	0	0	0	0	0	0
Reproductive system and breast disorders
ovarian cyst
alternative dictionary used: MedDRA 24.0
subjects affected / exposed ^[5]	0 / 130 (0.00%)	0 / 92 (0.00%)	1 / 10 (10.00%)	0 / 14 (0.00%)	0 / 68 (0.00%)	0 / 95 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)	0 / 15 (0.00%)	0 / 47 (0.00%)	0 / 2 (0.00%)	0 / 91 (0.00%)	0 / 2 (0.00%)	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 8 (0.00%)	0 / 57 (0.00%)	0 / 136 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Investigations
neutrophil count decreased
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 423 (0.24%)	0 / 348 (0.00%)	1 / 47 (2.13%)	0 / 54 (0.00%)	0 / 255 (0.00%)	0 / 318 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 53 (0.00%)	0 / 177 (0.00%)	0 / 9 (0.00%)	0 / 306 (0.00%)	0 / 10 (0.00%)	0 / 45 (0.00%)	1 / 42 (2.38%)	0 / 30 (0.00%)	1 / 4 (25.00%)	0 / 11 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 77 (0.00%)	0 / 25 (0.00%)	0 / 223 (0.00%)	0 / 453 (0.00%)
occurrences all number	1	0	2	0	0	0	0	2	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0
Injury, poisoning and procedural complications
contusion
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 423 (0.00%)	2 / 348 (0.57%)	1 / 47 (2.13%)	0 / 54 (0.00%)	0 / 255 (0.00%)	1 / 318 (0.31%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 53 (1.89%)	2 / 177 (1.13%)	1 / 9 (11.11%)	0 / 306 (0.00%)	0 / 10 (0.00%)	0 / 45 (0.00%)	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 77 (0.00%)	0 / 25 (0.00%)	1 / 223 (0.45%)	0 / 453 (0.00%)
occurrences all number	0	2	1	0	0	1	0	0	1	3	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
foreign body in eye
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 423 (0.00%)	0 / 348 (0.00%)	0 / 47 (0.00%)	0 / 54 (0.00%)	0 / 255 (0.00%)	0 / 318 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 53 (0.00%)	0 / 177 (0.00%)	0 / 9 (0.00%)	0 / 306 (0.00%)	0 / 10 (0.00%)	0 / 45 (0.00%)	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 77 (0.00%)	0 / 25 (0.00%)	0 / 223 (0.00%)	0 / 453 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
tendon rupture
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 423 (0.00%)	0 / 348 (0.00%)	0 / 47 (0.00%)	0 / 54 (0.00%)	0 / 255 (0.00%)	0 / 318 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 53 (0.00%)	0 / 177 (0.00%)	0 / 9 (0.00%)	0 / 306 (0.00%)	0 / 10 (0.00%)	0 / 45 (0.00%)	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 77 (0.00%)	0 / 25 (0.00%)	0 / 223 (0.00%)	0 / 453 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Cardiac disorders
tachycardia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 423 (0.00%)	1 / 348 (0.29%)	0 / 47 (0.00%)	0 / 54 (0.00%)	0 / 255 (0.00%)	1 / 318 (0.31%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 53 (0.00%)	0 / 177 (0.00%)	0 / 9 (0.00%)	1 / 306 (0.33%)	0 / 10 (0.00%)	0 / 45 (0.00%)	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 77 (0.00%)	0 / 25 (0.00%)	0 / 223 (0.00%)	0 / 453 (0.00%)
occurrences all number	0	1	0	0	0	1	0	0	0	0	0	2	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Blood and lymphatic system disorders
leukopenia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 423 (0.00%)	1 / 348 (0.29%)	0 / 47 (0.00%)	0 / 54 (0.00%)	0 / 255 (0.00%)	2 / 318 (0.63%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 53 (0.00%)	0 / 177 (0.00%)	0 / 9 (0.00%)	2 / 306 (0.65%)	0 / 10 (0.00%)	0 / 45 (0.00%)	0 / 42 (0.00%)	0 / 30 (0.00%)	1 / 4 (25.00%)	0 / 11 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 77 (0.00%)	0 / 25 (0.00%)	0 / 223 (0.00%)	1 / 453 (0.22%)
occurrences all number	0	1	0	0	0	2	0	1	0	0	0	2	0	0	0	0	1	0	0	0	0	0	0	0	0	1
Eye disorders
iridocyclitis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	5 / 423 (1.18%)	8 / 348 (2.30%)	2 / 47 (4.26%)	2 / 54 (3.70%)	7 / 255 (2.75%)	10 / 318 (3.14%)	0 / 6 (0.00%)	0 / 5 (0.00%)	3 / 53 (5.66%)	6 / 177 (3.39%)	0 / 9 (0.00%)	6 / 306 (1.96%)	0 / 10 (0.00%)	2 / 45 (4.44%)	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 77 (0.00%)	0 / 25 (0.00%)	1 / 223 (0.45%)	5 / 453 (1.10%)
occurrences all number	5	8	2	3	8	11	0	0	3	6	0	7	0	2	0	0	0	0	0	0	0	0	0	0	1	6
Gastrointestinal disorders
abdominal pain upper
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	2 / 423 (0.47%)	1 / 348 (0.29%)	0 / 47 (0.00%)	2 / 54 (3.70%)	0 / 255 (0.00%)	0 / 318 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 53 (1.89%)	0 / 177 (0.00%)	0 / 9 (0.00%)	0 / 306 (0.00%)	0 / 10 (0.00%)	0 / 45 (0.00%)	0 / 42 (0.00%)	2 / 30 (6.67%)	0 / 4 (0.00%)	0 / 11 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 77 (0.00%)	0 / 25 (0.00%)	0 / 223 (0.00%)	0 / 453 (0.00%)
occurrences all number	2	1	0	2	0	0	0	0	1	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0
crohn's disease
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 423 (0.00%)	0 / 348 (0.00%)	0 / 47 (0.00%)	0 / 54 (0.00%)	0 / 255 (0.00%)	0 / 318 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 53 (0.00%)	0 / 177 (0.00%)	0 / 9 (0.00%)	0 / 306 (0.00%)	0 / 10 (0.00%)	0 / 45 (0.00%)	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 77 (0.00%)	0 / 25 (0.00%)	1 / 223 (0.45%)	1 / 453 (0.22%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	1
diarrhoea
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	10 / 423 (2.36%)	3 / 348 (0.86%)	0 / 47 (0.00%)	3 / 54 (5.56%)	6 / 255 (2.35%)	5 / 318 (1.57%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 53 (1.89%)	2 / 177 (1.13%)	0 / 9 (0.00%)	3 / 306 (0.98%)	0 / 10 (0.00%)	0 / 45 (0.00%)	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 77 (0.00%)	0 / 25 (0.00%)	1 / 223 (0.45%)	1 / 453 (0.22%)
occurrences all number	10	4	0	3	6	6	0	0	1	2	0	3	0	0	0	0	0	0	0	0	0	0	0	0	1	1
toothache
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 423 (0.24%)	1 / 348 (0.29%)	0 / 47 (0.00%)	1 / 54 (1.85%)	1 / 255 (0.39%)	1 / 318 (0.31%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 53 (0.00%)	0 / 177 (0.00%)	0 / 9 (0.00%)	1 / 306 (0.33%)	0 / 10 (0.00%)	0 / 45 (0.00%)	0 / 42 (0.00%)	0 / 30 (0.00%)	1 / 4 (25.00%)	0 / 11 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 77 (1.30%)	0 / 25 (0.00%)	0 / 223 (0.00%)	0 / 453 (0.00%)
occurrences all number	1	1	0	1	1	1	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0	1	0	0	0
Skin and subcutaneous tissue disorders
cold urticaria
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 423 (0.00%)	0 / 348 (0.00%)	0 / 47 (0.00%)	0 / 54 (0.00%)	0 / 255 (0.00%)	0 / 318 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 53 (0.00%)	0 / 177 (0.00%)	0 / 9 (0.00%)	0 / 306 (0.00%)	0 / 10 (0.00%)	0 / 45 (0.00%)	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 77 (0.00%)	0 / 25 (0.00%)	0 / 223 (0.00%)	0 / 453 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
rash
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	5 / 423 (1.18%)	1 / 348 (0.29%)	0 / 47 (0.00%)	1 / 54 (1.85%)	1 / 255 (0.39%)	3 / 318 (0.94%)	0 / 6 (0.00%)	0 / 5 (0.00%)	3 / 53 (5.66%)	0 / 177 (0.00%)	0 / 9 (0.00%)	0 / 306 (0.00%)	0 / 10 (0.00%)	0 / 45 (0.00%)	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 77 (1.30%)	0 / 25 (0.00%)	0 / 223 (0.00%)	0 / 453 (0.00%)
occurrences all number	5	2	0	3	1	3	0	0	3	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
urticaria
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 423 (0.00%)	1 / 348 (0.29%)	0 / 47 (0.00%)	0 / 54 (0.00%)	1 / 255 (0.39%)	1 / 318 (0.31%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 53 (0.00%)	0 / 177 (0.00%)	0 / 9 (0.00%)	0 / 306 (0.00%)	0 / 10 (0.00%)	0 / 45 (0.00%)	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 77 (0.00%)	0 / 25 (0.00%)	1 / 223 (0.45%)	0 / 453 (0.00%)
occurrences all number	0	1	0	0	1	2	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0
Musculoskeletal and connective tissue disorders
arthralgia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	6 / 423 (1.42%)	8 / 348 (2.30%)	0 / 47 (0.00%)	1 / 54 (1.85%)	5 / 255 (1.96%)	14 / 318 (4.40%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 53 (0.00%)	4 / 177 (2.26%)	0 / 9 (0.00%)	2 / 306 (0.65%)	0 / 10 (0.00%)	1 / 45 (2.22%)	2 / 42 (4.76%)	1 / 30 (3.33%)	0 / 4 (0.00%)	1 / 11 (9.09%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 77 (1.30%)	0 / 25 (0.00%)	1 / 223 (0.45%)	5 / 453 (1.10%)
occurrences all number	6	9	0	1	7	16	0	0	0	4	0	4	0	1	2	1	0	1	0	0	0	0	1	0	1	6
back pain
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	15 / 423 (3.55%)	9 / 348 (2.59%)	1 / 47 (2.13%)	3 / 54 (5.56%)	3 / 255 (1.18%)	3 / 318 (0.94%)	0 / 6 (0.00%)	1 / 5 (20.00%)	2 / 53 (3.77%)	1 / 177 (0.56%)	1 / 9 (11.11%)	2 / 306 (0.65%)	0 / 10 (0.00%)	0 / 45 (0.00%)	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 77 (0.00%)	0 / 25 (0.00%)	2 / 223 (0.90%)	2 / 453 (0.44%)
occurrences all number	15	9	1	3	3	3	0	1	2	1	1	2	0	0	0	0	0	0	0	0	0	0	0	0	2	2
chondrodynia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 423 (0.00%)	0 / 348 (0.00%)	0 / 47 (0.00%)	0 / 54 (0.00%)	0 / 255 (0.00%)	0 / 318 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 53 (0.00%)	0 / 177 (0.00%)	0 / 9 (0.00%)	1 / 306 (0.33%)	0 / 10 (0.00%)	0 / 45 (0.00%)	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 77 (0.00%)	0 / 25 (0.00%)	0 / 223 (0.00%)	0 / 453 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0
enthesopathy
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	3 / 423 (0.71%)	3 / 348 (0.86%)	1 / 47 (2.13%)	1 / 54 (1.85%)	1 / 255 (0.39%)	0 / 318 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 53 (0.00%)	0 / 177 (0.00%)	0 / 9 (0.00%)	0 / 306 (0.00%)	0 / 10 (0.00%)	0 / 45 (0.00%)	0 / 42 (0.00%)	0 / 30 (0.00%)	1 / 4 (25.00%)	0 / 11 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 77 (0.00%)	0 / 25 (0.00%)	0 / 223 (0.00%)	0 / 453 (0.00%)
occurrences all number	3	3	1	1	1	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0
musculoskeletal stiffness
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 423 (0.00%)	0 / 348 (0.00%)	0 / 47 (0.00%)	0 / 54 (0.00%)	0 / 255 (0.00%)	0 / 318 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 53 (0.00%)	0 / 177 (0.00%)	0 / 9 (0.00%)	0 / 306 (0.00%)	0 / 10 (0.00%)	0 / 45 (0.00%)	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 77 (0.00%)	0 / 25 (0.00%)	0 / 223 (0.00%)	0 / 453 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
myalgia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 423 (0.00%)	2 / 348 (0.57%)	0 / 47 (0.00%)	0 / 54 (0.00%)	2 / 255 (0.78%)	3 / 318 (0.94%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 53 (0.00%)	0 / 177 (0.00%)	0 / 9 (0.00%)	2 / 306 (0.65%)	0 / 10 (0.00%)	0 / 45 (0.00%)	0 / 42 (0.00%)	2 / 30 (6.67%)	0 / 4 (0.00%)	0 / 11 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 77 (0.00%)	0 / 25 (0.00%)	0 / 223 (0.00%)	0 / 453 (0.00%)
occurrences all number	0	2	0	0	2	3	0	0	0	0	0	2	0	0	0	2	0	0	0	0	0	0	0	0	0	0
Infections and infestations
covid-19
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 423 (0.00%)	0 / 348 (0.00%)	0 / 47 (0.00%)	0 / 54 (0.00%)	0 / 255 (0.00%)	0 / 318 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 53 (0.00%)	0 / 177 (0.00%)	0 / 9 (0.00%)	3 / 306 (0.98%)	0 / 10 (0.00%)	0 / 45 (0.00%)	0 / 42 (0.00%)	1 / 30 (3.33%)	0 / 4 (0.00%)	0 / 11 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 77 (0.00%)	0 / 25 (0.00%)	0 / 223 (0.00%)	3 / 453 (0.66%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	3	0	0	0	1	0	0	0	0	0	1	0	0	0	3
gastrointestinal viral infection
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 423 (0.00%)	0 / 348 (0.00%)	0 / 47 (0.00%)	0 / 54 (0.00%)	0 / 255 (0.00%)	0 / 318 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 53 (0.00%)	0 / 177 (0.00%)	0 / 9 (0.00%)	0 / 306 (0.00%)	0 / 10 (0.00%)	0 / 45 (0.00%)	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 77 (0.00%)	0 / 25 (0.00%)	0 / 223 (0.00%)	0 / 453 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
nasopharyngitis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	40 / 423 (9.46%)	27 / 348 (7.76%)	2 / 47 (4.26%)	4 / 54 (7.41%)	27 / 255 (10.59%)	30 / 318 (9.43%)	0 / 6 (0.00%)	1 / 5 (20.00%)	7 / 53 (13.21%)	17 / 177 (9.60%)	1 / 9 (11.11%)	19 / 306 (6.21%)	0 / 10 (0.00%)	2 / 45 (4.44%)	1 / 42 (2.38%)	3 / 30 (10.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)	2 / 15 (13.33%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	2 / 77 (2.60%)	0 / 25 (0.00%)	4 / 223 (1.79%)	6 / 453 (1.32%)
occurrences all number	42	28	3	6	33	32	0	1	8	19	1	20	0	4	1	3	0	1	2	0	0	1	2	0	4	6
pharyngitis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	9 / 423 (2.13%)	5 / 348 (1.44%)	0 / 47 (0.00%)	0 / 54 (0.00%)	9 / 255 (3.53%)	7 / 318 (2.20%)	0 / 6 (0.00%)	0 / 5 (0.00%)	3 / 53 (5.66%)	3 / 177 (1.69%)	0 / 9 (0.00%)	6 / 306 (1.96%)	0 / 10 (0.00%)	1 / 45 (2.22%)	1 / 42 (2.38%)	0 / 30 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 77 (0.00%)	0 / 25 (0.00%)	0 / 223 (0.00%)	2 / 453 (0.44%)
occurrences all number	10	6	0	0	9	7	0	0	3	3	0	7	0	1	1	0	0	0	0	0	0	0	0	0	0	2
upper respiratory tract infection
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	22 / 423 (5.20%)	16 / 348 (4.60%)	2 / 47 (4.26%)	4 / 54 (7.41%)	7 / 255 (2.75%)	13 / 318 (4.09%)	0 / 6 (0.00%)	0 / 5 (0.00%)	2 / 53 (3.77%)	3 / 177 (1.69%)	1 / 9 (11.11%)	8 / 306 (2.61%)	0 / 10 (0.00%)	2 / 45 (4.44%)	1 / 42 (2.38%)	2 / 30 (6.67%)	0 / 4 (0.00%)	0 / 11 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	2 / 77 (2.60%)	0 / 25 (0.00%)	2 / 223 (0.90%)	1 / 453 (0.22%)
occurrences all number	24	19	3	4	7	14	0	0	2	3	1	10	0	2	1	2	0	0	0	0	0	0	2	0	2	1
vaginal infection
alternative dictionary used: MedDRA 24.0
subjects affected / exposed ^[6]	0 / 130 (0.00%)	0 / 92 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 68 (0.00%)	0 / 95 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)	0 / 15 (0.00%)	1 / 47 (2.13%)	0 / 2 (0.00%)	0 / 91 (0.00%)	0 / 2 (0.00%)	0 / 11 (0.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 8 (0.00%)	0 / 57 (0.00%)	1 / 136 (0.74%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1
Metabolism and nutrition disorders
glucose tolerance impaired
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 423 (0.00%)	0 / 348 (0.00%)	0 / 47 (0.00%)	0 / 54 (0.00%)	0 / 255 (0.00%)	0 / 318 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 53 (0.00%)	0 / 177 (0.00%)	0 / 9 (0.00%)	0 / 306 (0.00%)	1 / 10 (10.00%)	0 / 45 (0.00%)	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 77 (0.00%)	0 / 25 (0.00%)	0 / 223 (0.00%)	0 / 453 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0

Notes
[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: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been 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: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.

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Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Clinical Trial Results: A Multicenter, Long-Term Extension Study of 104 Weeks, Including a Double-Blind, Placebo-Controlled 40-Week Randomized Withdrawal-Retreatment Period, to Evaluate the Maintenance of Treatment Effect of Ixekizumab (LY2439821) in Patients with Axial Spondyloarthritis

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Participants who do not Experience a Flare (Combined Ixekizumab Treatment)

Primary: Percentage of Participants who do not Experience a Flare (Combined Ixekizumab Treatment)

Secondary: Percentage of Participants who do not Experience a Flare

Secondary: Percentage of Participants who do not Experience a Flare

Secondary: Change from Baseline in Modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS)

Secondary: Change from Baseline in Modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS)

Secondary: Percentage of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS)20 Response

Secondary: Percentage of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS)20 Response

Secondary: Percentage of Participants Achieving an ASAS40 Response

Secondary: Percentage of Participants Achieving an ASAS40 Response

Secondary: Percentage of Participants with Change of Ankylosing Spondylitis Disease Activity Score (ASDAS) ≥1.1 Units

Secondary: Percentage of Participants with Change of Ankylosing Spondylitis Disease Activity Score (ASDAS) ≥1.1 Units

Secondary: Percentage of Participants with Inactive Disease on the ASDAS (<1.3 Units)

Secondary: Percentage of Participants with Inactive Disease on the ASDAS (<1.3 Units)

Secondary: Change from Baseline in the Individual Components of the ASAS Criteria

Secondary: Change from Baseline in the Individual Components of the ASAS Criteria

Secondary: Percentage of Participants Achieving Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI50) Response

Secondary: Percentage of Participants Achieving Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI50) Response

Secondary: Change from Baseline in the Measure of High Sensitivity C-Reactive Protein (CRP)

Secondary: Change from Baseline in the Measure of High Sensitivity C-Reactive Protein (CRP)

Secondary: Change from Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI)

Secondary: Change from Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI)

Secondary: Change from Baseline in Chest Expansion in Centimeters

Secondary: Change from Baseline in Chest Expansion in Centimeters

Secondary: Change from Baseline in Occiput to Wall Distance

Secondary: Change from Baseline in Occiput to Wall Distance

Secondary: Change from Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES)

Secondary: Change from Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES)

Secondary: Change from Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Score

Secondary: Change from Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Score

Secondary: Change from Baseline in Severity of Peripheral Arthritis by Tender Joint Count (TJC) Score of 46 Joints

Secondary: Change from Baseline in Severity of Peripheral Arthritis by Tender Joint Count (TJC) Score of 46 Joints

Secondary: Change from Baseline in Severity of Peripheral Arthritis by Swollen Joint Count (SJC) Score of 44 Joints

Secondary: Change from Baseline in Severity of Peripheral Arthritis by Swollen Joint Count (SJC) Score of 44 Joints

Secondary: Percentage of Participants with Anterior Uveitis or Uveitis Flares

Secondary: Percentage of Participants with Anterior Uveitis or Uveitis Flares

Secondary: Change from Baseline in the Fatigue Numeric Rating Scale (NRS) Score

Secondary: Change from Baseline in the Fatigue Numeric Rating Scale (NRS) Score

Secondary: Change from Baseline on the Quick Inventory of Depressive Symptomatology Self-Report-16 (QIDS-SR16)

Secondary: Change from Baseline on the Quick Inventory of Depressive Symptomatology Self-Report-16 (QIDS-SR16)

Secondary: Change from Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) Score

Secondary: Change from Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) Score

Secondary: Change from Baseline in SF-36 Mental Component Summary (MCS) Score

Secondary: Change from Baseline in SF-36 Mental Component Summary (MCS) Score

Secondary: Change from Baseline in ASAS Health Index (ASAS HI)

Secondary: Change from Baseline in ASAS Health Index (ASAS HI)

Secondary: Change from Baseline in the European Quality of Life - 5 Dimensions 5 Level (EQ-5D-5L) UK population-based index score

Secondary: Change from Baseline in the European Quality of Life - 5 Dimensions 5 Level (EQ-5D-5L) UK population-based index score

Secondary: Change from Baseline in the Work Productivity Activity Impairment Spondyloarthritis (WPAI-SpA) Scores

Secondary: Change from Baseline in the Work Productivity Activity Impairment Spondyloarthritis (WPAI-SpA) Scores

Secondary: Change from Baseline in the Jenkins Sleep Evaluation Questionnaire (JSEQ)

Secondary: Change from Baseline in the Jenkins Sleep Evaluation Questionnaire (JSEQ)

Secondary: Percentage of Participants with No New Syndesmophyte Formation

Secondary: Percentage of Participants with No New Syndesmophyte Formation

Secondary: Percentage of Participants with Anti-Ixekizumab Antibodies

Secondary: Percentage of Participants with Anti-Ixekizumab Antibodies

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
A Multicenter, Long-Term Extension Study of 104 Weeks, Including a Double-Blind, Placebo-Controlled 40-Week Randomized Withdrawal-Retreatment Period, to Evaluate the Maintenance of Treatment Effect of Ixekizumab (LY2439821) in Patients with Axial Spondyloarthritis