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Clinical Trial Results:
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Comparing the Efficacy and Safety of LY2439821 to Etanercept and Placebo in Patients with Moderate-to-Severe Plaque Psoriasis

Summary
EudraCT number	2011-004350-26
Trial protocol	DE CZ ES NL AT PL GB
Global end of trial date	18 Jun 2019

Results information
Results version number	v1(current)
This version publication date	25 Jun 2020
First version publication date	25 Jun 2020
Other versions

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

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Trial information

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Sponsor protocol code

I1F-MC-RHBA

ISRCTN number

US NCT number

NCT01597245

WHO universal trial number (UTN)

Other trial identifiers

Trial Number: 12973

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

18 Jun 2019

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

18 Jun 2019

Was the trial ended prematurely?

Main objective of the trial

This study will assess the safety and efficacy of ixekizumab (LY2439821) compared to etanercept and placebo in participants with moderate to severe chronic plaque psoriasis.

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

18 May 2012

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Czech Republic: 18

Country: Number of subjects enrolled

Canada: 288

Country: Number of subjects enrolled

Austria: 23

Country: Number of subjects enrolled

Netherlands: 6

Country: Number of subjects enrolled

Romania: 35

Country: Number of subjects enrolled

United States: 369

Country: Number of subjects enrolled

Poland: 102

Country: Number of subjects enrolled

United Kingdom: 33

Country: Number of subjects enrolled

Australia: 51

Country: Number of subjects enrolled

France: 65

Country: Number of subjects enrolled

Germany: 179

Country: Number of subjects enrolled

Spain: 55

Worldwide total number of subjects

1224

EEA total number of subjects

516

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)

1147

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

No Text Available

Screening details

This study has 5 periods: Period 1 - Screening; Period 2 - Blinded Induction Dosing Period (Weeks 0 to 12); Period 3 - Blinded Maintenance Dosing Period (Weeks 12 - 60); Period 4 - Long-Term Extension Period (Weeks 60 - 264); Period 5 - Post-Treatment Follow-Up Period (A Minimum of 12 Weeks)

Period 1 title

Induction Period (Week 0 - Week 12)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

Placebo - Induction Period

Arm description

Placebo was administered as 2 subcutaneous (SC) injections at week 0, followed by 1 injection at weeks 2, 4, 6, 8, 10. Placebo for ETN (1 SC injection) administered twice weekly (every 3 to 4 days) starting at Week 0 up to Week 12.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

50 mg Etanercept (ETN) - Induction Period

Arm description

50 milligrams (mg) ETN was administered by 1 SC injection twice weekly (every 3-4 days) up to Week 12. Placebo for ixe was administered as 2 SC injections at Week 0 followed by Placebo for ixe administered as 1 SC injection Q2W (Weeks 2, 4, 6, 8, and 10).

Arm type

Active comparator

Investigational medicinal product name

Etanercept

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

50 milligrams (mg) ETN was administered by 1 SC injection twice weekly (every 3-4 days) up to Week 12.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Placebo for ixe was administered as 2 SC injections at Week 0 followed by Placebo for ixe administered as 1 SC injection Q2W (Weeks 2, 4, 6, 8, and 10).

Ixe Q4W - Induction Period

Arm description

160 mg ixe was administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection every 4 weeks (Q4W:Weeks 4 and 8). Placebo was administered as 1 SC injection at Weeks 2, 6, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12.

Arm type

Experimental

Investigational medicinal product name

Ixekizumab (Ixe)

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

160 mg ixe was administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection every 4 weeks (Q4W:Weeks 4 and 8).

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Placebo was administered as 1 SC injection at Weeks 2, 6, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12.

Ixe Q2W - Induction Period

Arm description

160 mg ixe administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection Q2W at Weeks 2, 4, 6, 8, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12.

Arm type

Experimental

Investigational medicinal product name

Ixekizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

160 mg ixe administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection Q2W at Weeks 2, 4, 6, 8, and 10.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12.

Number of subjects in period 1	Placebo - Induction Period	50 mg Etanercept (ETN) - Induction Period	Ixe Q4W - Induction Period	Ixe Q2W - Induction Period
Started	168	358	347	351
Received at least 1 dose of study drug	167	357	347	350
Completed	158	333	328	342
Not completed	10	25	19	9
Consent withdrawn by subject	2	8	6	2
Physician decision	1	-	-	1
Adverse event, non-fatal	1	5	5	4
Lost to follow-up	1	5	2	-
Protocol deviation	2	4	5	2
Lack of efficacy	3	3	1	-

Period 2 title

Maintenance Period (Week 12 to Week 60)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Ixe/Placebo- Maintenance Period Primary Population (Pop)

Arm description

Participants who received 80 mg ixe Q2W or Q4W in Induction Period (Weeks 0 to 10) and classified as responders were administered placebo as 2 SC injections at Week 12 followed by placebo as 1 SC injection Q4W up to and including Week 56.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Ixe/Ixe Q4W - Maintenance Period Primary Pop

Arm description

Arm type

Experimental

Investigational medicinal product name

Ixekizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants who received 80 mg ixe Q2W or Q4W in Induction Period (Weeks 0 to 10) and classified as responders were administered 80 mg ixe as 1 SC injection, Q4W from Weeks 12 - 56.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Placebo for ixe injection at Week 12 followed by 80 mg ixe as 1 SC injection Q4W up to and including Week 56.

Ixe/Ixe Q12W - Maintenance Period Primary Pop

Arm description

Participants who received 80 mg ixe Q2W or Q4W in Induction Period (Weeks 0 to 10) and classified as responders were administered 80 mg ixe as 1 SC injection and a Placebo for ixe injection at Week 12 followed by 80 mg ixe as 1 SC injection every 12 weeks (Q12W) up to and including Week 56. To maintain blinding with Q4W dose regimen, Placebo for ixe given as 1 SC injection at Weeks 16, 20, 28, 32, 40, 44, 52, and 56.

Arm type

Experimental

Investigational medicinal product name

Ixekizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants who received 80 mg ixe Q2W or Q4W in Induction Period (Weeks 0 to 10) and classified as responders were administered 80 mg ixe as 1 SC injection and followed by 80 mg ixe as 1 SC injection every 12 weeks (Q12W) up to and including Week 56.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Placebo for ixe injection at Week 12. To maintain blinding with Q4W dose regimen, Placebo for ixe given as 1 SC injection at Weeks 16, 20, 28, 32, 40, 44, 52, and 56.

Placebo Resp/Placebo - Maintenance Period Secondary Pop

Arm description

Participants who received placebo during the Induction Period (Weeks 0 to 10) and classified as responders and were administered placebo as 2 SC injections at Week 12 followed by placebo as 1 SC injection Q4W up to and including Week 56.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Placebo NonResp/Ixe Q4W - Maintenance Period Secondary Pop

Arm description

Participants who received placebo in Induction Period (Weeks 0 to 10) and classified as non-responders (NonResp) were administered 160 mg ixe as 2 SC injections at Week 12 followed by 80 mg ixe as 1 SC injection Q4W up to and including Week 56.

Arm type

Experimental

Investigational medicinal product name

Ixekizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

ETN Resp/Placebo Maintenance Period Secondary Pop

Arm description

Participants who received ETN during the Induction Period (Weeks 0 to 10) and classified as responders and were administered placebo as 2 SC injections at Week 12 followed by placebo as 1 SC injection Q4W up to and including Week 56.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

ETN NonResp/Ixe Q4W - Maintenance Period Secondary Pop

Arm description

Participants who received ETN in Induction Period (Weeks 0 to 12) and classified as non-responders were administered 2 SC injections of placebo at Week 12 followed by 80 mg ixe as 1 SC injection Q4W up to and including Week 56.

Arm type

Experimental

Investigational medicinal product name

Ixekizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

80 mg ixe as 1 SC injection Q4W from Weeks 16 - 60.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

2 SC injections of placebo were administered at Week 12.

Ixe Q4W NonResp/Ixe Q4W- Maintenance Period Secondary Pop

Arm description

Participants who received 80 mg ixe Q4W in Induction Period (Weeks 0 to 10) and classified as non-responders were administered 80 mg ixe as 1 SC injection and a Placebo for ixe injection at Week 12 followed by 80 mg ixe as 1 SC injection Q4W up to and including Week 56.

Arm type

Experimental

Investigational medicinal product name

Ixekizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants who received 80 mg ixe Q4W in Induction Period (Weeks 0 to 10) and classified as non-responders were administered 80 mg ixe as 1 SC injection at Week 12 followed by 80 mg ixe as 1 SC injection Q4W up to and including Week 56.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Placebo for ixe injection at Week 12 followed by 80 mg ixe as 1 SC injection Q4W up to and including Week 56.

Ixe Q2W NonResp/Ixe Q4W - Maintenance Period Secondary Pop

Arm description

Participants who received 80 mg ixe Q2W in Induction Period (Weeks 0 to 10) and classified as non-responders were administered 80 mg ixe as 1 SC injection and a Placebo for ixe injection at Week 12 followed by 80 mg ixe as 1 SC injection Q4W up to and including Week 56.

Arm type

Experimental

Investigational medicinal product name

Ixekizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants who received 80 mg ixe Q2W in Induction Period (Weeks 0 to 10) and classified as non-responders were administered 80 mg ixe as 1 SC injection at Week 12 followed by 80 mg ixe as 1 SC injection Q4W up to and including Week 56.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Placebo for ixe injection at Week 12 followed by 80 mg ixe as 1 SC injection Q4W up to and including Week 56.

Number of subjects in period 2	Ixe/Placebo- Maintenance Period Primary Population (Pop)	Ixe/Ixe Q4W - Maintenance Period Primary Pop	Ixe/Ixe Q12W - Maintenance Period Primary Pop	Placebo Resp/Placebo - Maintenance Period Secondary Pop	Placebo NonResp/Ixe Q4W - Maintenance Period Secondary Pop	ETN Resp/Placebo Maintenance Period Secondary Pop	ETN NonResp/Ixe Q4W - Maintenance Period Secondary Pop	Ixe Q4W NonResp/Ixe Q4W- Maintenance Period Secondary Pop	Ixe Q2W NonResp/Ixe Q4W - Maintenance Period Secondary Pop
Started	176	187	181	3	155	132	200	75	49
Participants received one dose	176	187	181	3	155	132	200	75	49
Completed	15	149	92	0	135	11	178	56	37
Not completed	161	38	89	3	20	121	22	19	12
Consent withdrawn by subject	3	3	1	-	4	1	6	5	4
Physician decision	-	1	-	-	1	1	1	1	-
Relapsed	150	22	80	2	-	114	-	-	-
Adverse event, non-fatal	4	6	6	1	8	2	8	1	2
On study treatment	-	1	1	-	-	-	-	-	-
Sponsor Decision	-	-	-	-	-	-	1	-	-
Lost to follow-up	3	4	1	-	1	2	2	2	1
Protocol deviation	1	-	-	-	3	1	2	-	1
Lack of efficacy	-	1	-	-	3	-	2	10	4

Period 3 title

Long Term Extension (Week 60 - Week 264)

Is this the baseline period?

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Placebo Long-Term Extension (LTE)

Arm description

Participants who received placebo at the start of long-term extension period (Week 60) and could be switched to ixe. Data while participants were on placebo were included.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants who received placebo at the start of long-term extension period (Week 60) and could be switched to ixe. Data while participants were on placebo were included.

Ixe Long-Term Extension

Arm description

Participants who received 80 mg ixe in all dosing regimens at the start of the long-term extension period from Week 60 to Week 264.

Arm type

Experimental

Investigational medicinal product name

Ixekizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants who received 80 mg ixe in all dosing regimens at the start of the long-term extension period from Week 60 to Week 264.

Total Ixe Long-term Extension

Arm description

Participants who received at least 1 dose of 80 mg ixe in all dosing regimens during the long-term extension period from Week 60 to Week 264, including those who have switched from PBO to Ixe in long-term extension (LTE) period.

Arm type

Experimental

Investigational medicinal product name

Ixekizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Number of subjects in period 3	Placebo Long-Term Extension (LTE)	Ixe Long-Term Extension	Total Ixe Long-term Extension
Started	26	979	1002
Completed	0	754	774
Not completed	26	225	228
Adverse event, serious fatal	-	8	8
Consent withdrawn by subject	1	62	63
Physician decision	1	11	12
Clinical Relapse	-	4	4
Adverse event, non-fatal	1	69	70
Switched from PBO to Ixe	23	-	-
Sponsor Decision	-	1	1
Lost to follow-up	-	38	38
Lack of efficacy	-	26	26
Protocol deviation	-	6	6

Period 4 title

Post-Treatment Follow-Up (12 - 24 Weeks)

Is this the baseline period?

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Placebo Post-Treatment Follow-Up

Arm description

Participants who received PBO immediately prior to entering the Post-Treatment Follow-Up period (a 12-24 week period after their last scheduled treatment visit).

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Subcutaneous use

Dosage and administration details

Participants who received PBO immediately prior to entering the Post-Treatment Follow-Up period (a 12-24 week period after their last scheduled treatment visit).

ETN Post-Treatment Follow-Up

Arm description

Participants who received ETN immediately prior to entering the Post-Treatment Follow-Up period (a 12-24 week period after their last scheduled treatment visit).

Arm type

Active comparator

Investigational medicinal product name

Etancercept

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants who received ETN immediately prior to entering the Post-Treatment Follow-Up period (a 12-24 week period after their last scheduled treatment visit).

Ixe Q12W Post-Treatment Follow-Up

Arm description

Participants who received 80 mg ixe 1 SC injection Q12W immediately prior to entering the Post-Treatment Follow-Up period (a 12-24 week period after their last scheduled treatment visit).

Arm type

Experimental

Investigational medicinal product name

Ixekizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants who received 80 mg ixe 1 SC injection Q12W immediately prior to entering the Post-Treatment Follow-Up period (a 12-24 week period after their last scheduled treatment visit).

Ixe Q4W Post-Treatment Follow-Up

Arm description

Participants who received 80 mg ixe 1 SC injection Q4W immediately prior to entering the Post-Treatment Follow-Up period (a 12-24 week period after their last scheduled treatment visit).

Arm type

Experimental

Investigational medicinal product name

Ixekizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants who received 80 mg ixe 1 SC injection Q4W immediately prior to entering the Post-Treatment Follow-Up period (a 12-24 week period after their last scheduled treatment visit).

Ixe Q2W Post-Treatment Follow-Up

Arm description

Participants who received 80 mg ixe 1 SC injection Q2W immediately prior to entering the Post-Treatment Follow-Up period (a 12-24 week period after their last scheduled treatment visit).

Arm type

Experimental

Investigational medicinal product name

Ixekizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants who received 80 mg ixe 1 SC injection Q2W immediately prior to entering the Post-Treatment Follow-Up period (a 12-24 week period after their last scheduled treatment visit).

Number of subjects in period 4	Placebo Post-Treatment Follow-Up	ETN Post-Treatment Follow-Up	Ixe Q12W Post-Treatment Follow-Up	Ixe Q4W Post-Treatment Follow-Up	Ixe Q2W Post-Treatment Follow-Up
Started	16	6	24	656	248
Completed	0	0	14	489	212
Not completed	16	6	10	167	36
Physician decision	1	-	-	9	1
Consent withdrawn by subject	-	1	1	41	13
Clinical Relapse	-	-	-	1	-
Adverse event, non-fatal	9	5	8	63	13
Sponsor Decision	1	-	-	1	-
Lost to follow-up	-	-	1	14	4
Entry Criteria Not Met	2	-	-	3	-
Lack of efficacy	2	-	-	29	3
Protocol deviation	1	-	-	6	2

Baseline characteristics

Top of page

Reporting group title

Placebo - Induction Period

Reporting group description

Reporting group title

50 mg Etanercept (ETN) - Induction Period

Reporting group description

Reporting group title

Ixe Q4W - Induction Period

Reporting group description

Reporting group title

Ixe Q2W - Induction Period

Reporting group description

Reporting group values	Placebo - Induction Period	50 mg Etanercept (ETN) - Induction Period	Ixe Q4W - Induction Period	Ixe Q2W - Induction Period	Total
Number of subjects	168	358	347	351	1224
Age categorical
Units: Subjects
In utero	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0
Adults (18-64 years)	159	337	324	327	1147
From 65-84 years	9	21	23	24	77
85 years and over	0	0	0	0	0
Gender categorical
Units: Subjects
Female	48	122	103	130	403
Male	120	236	244	221	821
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	11	26	24	19	80
Not Hispanic or Latino	130	279	271	274	954
Unknown or Not Reported	27	53	52	58	190
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	2	0	2	2	6
Asian	6	8	11	12	37
Native Hawaiian or Other Pacific Islander	1	1	1	0	3
Black or African American	10	13	11	5	39
White	149	331	315	330	1125
More than one race	0	1	3	1	5
Unknown or Not Reported	0	4	4	1	9
Region of Enrollment
Units: Subjects
Canada	40	82	82	84	288
Austria	2	10	6	5	23
Netherlands	1	2	2	1	6
Czechia	3	6	3	6	18
Romania	6	9	8	12	35
United States	49	111	105	104	369
Poland	14	30	28	30	102
United Kingdom	4	9	9	11	33
Australia	7	13	15	16	51
France	7	18	21	19	65
Germany	28	53	51	47	179
Spain	7	15	17	16	55
Baseline in Static Physician Global Assessment (sPGA)
The sPGA is the physician's determination of the participant's Ps lesions overall at a given time point. The sPGA is recommended as an endpoint to use to assess efficacy in the treatment of Ps (EMEA 2004). Overall lesions are categorized by descriptions for induration, erythema, and scaling. For the analysis of responses, the participant's Ps is assessed at a given time point on a 6-point scale in which 0 = cleared, 1 = minimal, 2 = mild, 3 = moderate; 4 = severe, 5 = very severe.
Units: Subjects
sPGA = 3	86	186	166	178	616
sPGA = 4, 5	82	172	181	173	608
Baseline in Participants Achieving Psoriasis Area and Severity Index (PASI) Score
PASI is another accepted primary efficacy measurement for this phase of development of Ps treatments. The PASI combines assessments of the extent of body-surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of desquamation, erythema, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 or no Ps to 72 for the most severe disease.
Units: units on a scale
arithmetic mean (standard deviation)	20.57 ± 8.366	19.07 ± 6.701	20.04 ± 6.962	19.35 ± 7.339	-
Baseline Dermatology-Specific Quality of Life Index (DLQI) Total Score
DLQI is a participant-administered, 10-question, validated, quality-of-life questionnaire that covers 6 domains, including symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories include 0 (not at all), 1 (a little), 2 (a lot), and 3 (very much) and unanswered ("not relevant") responses were scored as "0." Total scores range from 0 to 30, with higher score indicating greater quality of life impairment.
Units: units on a scale
arithmetic mean (standard deviation)	12.8 ± 7.24	12.7 ± 7.03	11.6 ± 6.65	12.4 ± 6.86	-
Baseline in Nail Psoriasis Severity Index (NAPSI) Total Score
The NAPSI scale evaluates Ps severity in the fingernail bed and fingernail matrix with each divided into quadrants. Scores range from 0 (none) to 4 (Ps in all 4 quadrants), depending on the presence (score of 1) or absence (score of 0) of Ps in each quadrant of the fingernail bed or matrix. NAPSI score of a fingernail is the sum of scores from each quadrant of the fingernail bed and fingernail matrix (maximum of 8). The total NAPSI score equals the sum of all fingernails and ranges from 0 to 80. Higher scores indicate more severe Ps.
Units: units on a scale
arithmetic mean (standard deviation)	27.62 ± 20.937	30.44 ± 20.648	23.70 ± 18.696	26.27 ± 20.388	-
Baseline in Psoriasis Scalp Severity Index (PSSI) Total Score
The PSSI is a physician assessment of erythema, induration and desquamation and percent of scalp that is covered with a scores range from 0 (none) to 4 (very severe). The composite score is derived from the sum of scores for erythema, induration, and desquamation multiplied by the score recorded for the extent of the scalp area involved, 1 (<10%) to 6 (90%-100%) with a total score ranging from 0 (less severity) to 72 (more severity).
Units: units on a scale
arithmetic mean (standard deviation)	21.0 ± 15.24	20.0 ± 15.19	20.8 ± 15.63	19.5 ± 14.85	-
Baseline in Body Surface Area (BSA) Total Score
BSA is a physician rating of the percentage of involvement of Ps for each participant. BSA is assessed on a continuous scale from 0% (no involvement) to 100% (full involvement), where 1% corresponds to the size of the participant's hand (includes the palm, fingers and thumb). Total BSA is the sum of handprints from the affected areas.
Units: units on a scale
arithmetic mean (standard deviation)	27.2 ± 18.12	25.3 ± 15.50	27.0 ± 17.23	25.1 ± 15.82	-
Baseline in Quick Inventory of Depressive Symptomatology Self Report 16 items (QIDS-SR16) Score
QIDS-SR16 is a participant-administered, 16-item instrument assesses the existence and severity of symptoms of depression. A participant is asked a statement relating to the way they have felt for the past 7 days and rate on a 4-point scale: 0 (best) to 3 (worst). The sum of the domains [sad mood, concentration, self-criticism, suicidal ideation, interest, energy/fatigue, sleep disturbance, decrease/increase in appetite/weight, and psychomotor agitation/retardation] to give a single total scores range from 0 to 27, with higher scores indicating greater symptom severity.
Units: units on a scale
arithmetic mean (standard deviation)	4.7 ± 4.14	4.5 ± 4.07	4.4 ± 4.04	4.6 ± 3.84	-
Baseline in Patient's Global Assessment (PatGA) Total Score
The PatGA is a single-item self-reported instrument asking the participant to rate the severity of their psoriasis "today" by circling a number on the numeric rating scale from 0 (Clear = no psoriasis) to 5 (Severe = the worst their psoriasis has ever been).
Units: units on a scale
arithmetic mean (standard deviation)	4.0 ± 0.92	4.0 ± 0.96	4.1 ± 0.90	4.1 ± 0.91	-
Baseline in Work Productivity Activity Impairment - Psoriasis
Absenteeism Score
Units: units on a scale
arithmetic mean (standard deviation)	4.3 ± 16.61	3.7 ± 15.24	4.6 ± 17.65	7.3 ± 22.15	-
Baseline in Work Productivity Activity Impairment Questionnaire - Psoriasis
Active Impairment Score
Units: units on a scale
arithmetic mean (standard deviation)	30.2 ± 28.87	31.3 ± 29.04	29.4 ± 29.28	31.7 ± 29.64	-
Baseline in Work Productivity Impairment Questionnaire - Psoriasis
Presenteeism Score
Units: units on a scale
arithmetic mean (standard deviation)	24.3 ± 26.19	21.2 ± 25.42	22.3 ± 24.77	24.2 ± 25.80	-
Baseline in Work Productivity Activity Impairment Questionnaire-Psoriasis
Work Productivity Loss
Units: units on a scale
arithmetic mean (standard deviation)	26.1 ± 28.11	22.3 ± 26.52	24.6 ± 27.41	27.7 ± 29.19	-
Baseline in Short form (36 Items) Health Survey SF-36 Total Score
The SF-36 is a self-reported instrument that measures the participant's health status during the previous 7 days. It comprises 36-items covering 8 domains: physical functioning, role physical, role emotional, bodily pain, vitality, social functioning, mental health, and general health. Items are answered on Likert scales of varying lengths. The 8 domains are regrouped in the Physical Component Score (PCS) and Mental Component Score (MCS) scores. Scores range from 0 to 100, with higher scores indicating better levels of function and/or better health. Physical Summary Score
Units: units on a scale
arithmetic mean (standard deviation)	47.7094 ± 9.5043	47.5268 ± 9.0729	47.6231 ± 8.9693	47.6996 ± 9.03332	-
Baseline in SF-36 Total Score
Mental Summary Score
Units: units on a scale
arithmetic mean (standard deviation)	47.7889 ± 10.6183	48.7097 ± 10.6546	49.0131 ± 10.9087	47.7140 ± 11.6686	-

Subject analysis set title

Total Participants

Subject analysis set type

Full analysis

Subject analysis set description

All participants with evaluable data.

Subject analysis sets values	Total Participants
Number of subjects	1224
Age categorical
Units: Subjects
In utero
Preterm newborn infants (gestational age < 37 wks)
Newborns (0-27 days)
Infants and toddlers (28 days-23 months)
Children (2-11 years)
Adolescents (12-17 years)
Adults (18-64 years)
From 65-84 years
85 years and over
Age continuous
Units: years
arithmetic mean (standard deviation)	±
Gender categorical
Units: Subjects
Female
Male
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino
Not Hispanic or Latino
Unknown or Not Reported
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native
Asian
Native Hawaiian or Other Pacific Islander
Black or African American
White
More than one race
Unknown or Not Reported
Region of Enrollment
Units: Subjects
Canada
Austria
Netherlands
Czechia
Romania
United States
Poland
United Kingdom
Australia
France
Germany
Spain
Baseline in Static Physician Global Assessment (sPGA)
The sPGA is the physician's determination of the participant's Ps lesions overall at a given time point. The sPGA is recommended as an endpoint to use to assess efficacy in the treatment of Ps (EMEA 2004). Overall lesions are categorized by descriptions for induration, erythema, and scaling. For the analysis of responses, the participant's Ps is assessed at a given time point on a 6-point scale in which 0 = cleared, 1 = minimal, 2 = mild, 3 = moderate; 4 = severe, 5 = very severe.
Units: Subjects
sPGA = 3
sPGA = 4, 5
Baseline in Participants Achieving Psoriasis Area and Severity Index (PASI) Score
PASI is another accepted primary efficacy measurement for this phase of development of Ps treatments. The PASI combines assessments of the extent of body-surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of desquamation, erythema, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 or no Ps to 72 for the most severe disease.
Units: units on a scale
arithmetic mean (standard deviation)	19.63 ± 7.216
Baseline Dermatology-Specific Quality of Life Index (DLQI) Total Score
DLQI is a participant-administered, 10-question, validated, quality-of-life questionnaire that covers 6 domains, including symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories include 0 (not at all), 1 (a little), 2 (a lot), and 3 (very much) and unanswered ("not relevant") responses were scored as "0." Total scores range from 0 to 30, with higher score indicating greater quality of life impairment.
Units: units on a scale
arithmetic mean (standard deviation)	12.3 ± 6.91
Baseline in Nail Psoriasis Severity Index (NAPSI) Total Score
The NAPSI scale evaluates Ps severity in the fingernail bed and fingernail matrix with each divided into quadrants. Scores range from 0 (none) to 4 (Ps in all 4 quadrants), depending on the presence (score of 1) or absence (score of 0) of Ps in each quadrant of the fingernail bed or matrix. NAPSI score of a fingernail is the sum of scores from each quadrant of the fingernail bed and fingernail matrix (maximum of 8). The total NAPSI score equals the sum of all fingernails and ranges from 0 to 80. Higher scores indicate more severe Ps.
Units: units on a scale
arithmetic mean (standard deviation)	26.97 ± 20.211
Baseline in Psoriasis Scalp Severity Index (PSSI) Total Score
The PSSI is a physician assessment of erythema, induration and desquamation and percent of scalp that is covered with a scores range from 0 (none) to 4 (very severe). The composite score is derived from the sum of scores for erythema, induration, and desquamation multiplied by the score recorded for the extent of the scalp area involved, 1 (<10%) to 6 (90%-100%) with a total score ranging from 0 (less severity) to 72 (more severity).
Units: units on a scale
arithmetic mean (standard deviation)	20.2 ± 15.22
Baseline in Body Surface Area (BSA) Total Score
BSA is a physician rating of the percentage of involvement of Ps for each participant. BSA is assessed on a continuous scale from 0% (no involvement) to 100% (full involvement), where 1% corresponds to the size of the participant's hand (includes the palm, fingers and thumb). Total BSA is the sum of handprints from the affected areas.
Units: units on a scale
arithmetic mean (standard deviation)	26.0 ± 16.47
Baseline in Quick Inventory of Depressive Symptomatology Self Report 16 items (QIDS-SR16) Score
QIDS-SR16 is a participant-administered, 16-item instrument assesses the existence and severity of symptoms of depression. A participant is asked a statement relating to the way they have felt for the past 7 days and rate on a 4-point scale: 0 (best) to 3 (worst). The sum of the domains [sad mood, concentration, self-criticism, suicidal ideation, interest, energy/fatigue, sleep disturbance, decrease/increase in appetite/weight, and psychomotor agitation/retardation] to give a single total scores range from 0 to 27, with higher scores indicating greater symptom severity.
Units: units on a scale
arithmetic mean (standard deviation)	4.5 ± 4.00
Baseline in Patient's Global Assessment (PatGA) Total Score
The PatGA is a single-item self-reported instrument asking the participant to rate the severity of their psoriasis "today" by circling a number on the numeric rating scale from 0 (Clear = no psoriasis) to 5 (Severe = the worst their psoriasis has ever been).
Units: units on a scale
arithmetic mean (standard deviation)	4.0 ± 0.92
Baseline in Work Productivity Activity Impairment - Psoriasis
Absenteeism Score
Units: units on a scale
arithmetic mean (standard deviation)	5.1 ± 18.40
Baseline in Work Productivity Activity Impairment Questionnaire - Psoriasis
Active Impairment Score
Units: units on a scale
arithmetic mean (standard deviation)	30.7 ± 29.24
Baseline in Work Productivity Impairment Questionnaire - Psoriasis
Presenteeism Score
Units: units on a scale
arithmetic mean (standard deviation)	22.8 ± 25.44
Baseline in Work Productivity Activity Impairment Questionnaire-Psoriasis
Work Productivity Loss
Units: units on a scale
arithmetic mean (standard deviation)	25.0 ± 27.82
Baseline in Short form (36 Items) Health Survey SF-36 Total Score
The SF-36 is a self-reported instrument that measures the participant's health status during the previous 7 days. It comprises 36-items covering 8 domains: physical functioning, role physical, role emotional, bodily pain, vitality, social functioning, mental health, and general health. Items are answered on Likert scales of varying lengths. The 8 domains are regrouped in the Physical Component Score (PCS) and Mental Component Score (MCS) scores. Scores range from 0 to 100, with higher scores indicating better levels of function and/or better health. Physical Summary Score
Units: units on a scale
arithmetic mean (standard deviation)	47.6289 ± 9.0814
Baseline in SF-36 Total Score
Mental Summary Score
Units: units on a scale
arithmetic mean (standard deviation)	48.3832 ± 11.0234

End points

Top of page

Reporting group title

Placebo - Induction Period

Reporting group description

Reporting group title

50 mg Etanercept (ETN) - Induction Period

Reporting group description

Reporting group title

Ixe Q4W - Induction Period

Reporting group description

Reporting group title

Ixe Q2W - Induction Period

Reporting group description

Reporting group title

Ixe/Placebo- Maintenance Period Primary Population (Pop)

Reporting group description

Reporting group title

Ixe/Ixe Q4W - Maintenance Period Primary Pop

Reporting group description

Reporting group title

Ixe/Ixe Q12W - Maintenance Period Primary Pop

Reporting group description

Reporting group title

Placebo Resp/Placebo - Maintenance Period Secondary Pop

Reporting group description

Reporting group title

Placebo NonResp/Ixe Q4W - Maintenance Period Secondary Pop

Reporting group description

Reporting group title

ETN Resp/Placebo Maintenance Period Secondary Pop

Reporting group description

Reporting group title

ETN NonResp/Ixe Q4W - Maintenance Period Secondary Pop

Reporting group description

Reporting group title

Ixe Q4W NonResp/Ixe Q4W- Maintenance Period Secondary Pop

Reporting group description

Reporting group title

Ixe Q2W NonResp/Ixe Q4W - Maintenance Period Secondary Pop

Reporting group description

Reporting group title

Placebo Long-Term Extension (LTE)

Reporting group description

Participants who received placebo at the start of long-term extension period (Week 60) and could be switched to ixe. Data while participants were on placebo were included.

Reporting group title

Ixe Long-Term Extension

Reporting group description

Participants who received 80 mg ixe in all dosing regimens at the start of the long-term extension period from Week 60 to Week 264.

Reporting group title

Total Ixe Long-term Extension

Reporting group description

Reporting group title

Placebo Post-Treatment Follow-Up

Reporting group description

Participants who received PBO immediately prior to entering the Post-Treatment Follow-Up period (a 12-24 week period after their last scheduled treatment visit).

Reporting group title

ETN Post-Treatment Follow-Up

Reporting group description

Participants who received ETN immediately prior to entering the Post-Treatment Follow-Up period (a 12-24 week period after their last scheduled treatment visit).

Reporting group title

Ixe Q12W Post-Treatment Follow-Up

Reporting group description

Participants who received 80 mg ixe 1 SC injection Q12W immediately prior to entering the Post-Treatment Follow-Up period (a 12-24 week period after their last scheduled treatment visit).

Reporting group title

Ixe Q4W Post-Treatment Follow-Up

Reporting group description

Participants who received 80 mg ixe 1 SC injection Q4W immediately prior to entering the Post-Treatment Follow-Up period (a 12-24 week period after their last scheduled treatment visit).

Reporting group title

Ixe Q2W Post-Treatment Follow-Up

Reporting group description

Participants who received 80 mg ixe 1 SC injection Q2W immediately prior to entering the Post-Treatment Follow-Up period (a 12-24 week period after their last scheduled treatment visit).

Subject analysis set title

Total Participants

Subject analysis set type

Full analysis

Subject analysis set description

All participants with evaluable data.

Primary: Percentage of Participants with a Static Physician Global Assessment (sPGA) of (0,1) (Efficacy of ixekizumab in participants with moderate to severe chronic plaque psoriasis. Measure: Static Physician Global Assessment [sPGA])

Top of page

End point title

Percentage of Participants with a Static Physician Global Assessment (sPGA) of (0,1) (Efficacy of ixekizumab in participants with moderate to severe chronic plaque psoriasis. Measure: Static Physician Global Assessment [sPGA])

End point description

The sPGA is the physician's determination of the participant's Psoriasis (Ps) lesions overall at a given time point. Lesions were categorized by descriptions for induration, erythema, and scaling. Participant's Ps was assessed as 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), or 5 (very severe). An sPGA responder was defined as having a post-baseline sPGA score of “0” or “1” with at least a 2-point improvement from baseline. Participants who did not meet the clinical response criteria or had missing data at Week 12 were considered non-responders for Non-Responder Imputation (NRI) analysis.

End point type

Primary

End point timeframe

Week 12

End point values	Placebo - Induction Period	50 mg Etanercept (ETN) - Induction Period	Ixe Q4W - Induction Period	Ixe Q2W - Induction Period
Number of subjects analysed	168 ^[1]	358 ^[2]	347 ^[3]	351 ^[4]
Units: percentage of participants
number (not applicable)	2.4	36.0	72.9	83.2

Notes
[1] - All randomized participants.
[2] - All randomized participants.
[3] - All randomized participants.
[4] - All randomized participants.

sPGA Statistical Analysis 1

Comparison groups

Placebo - Induction Period v 50 mg Etanercept (ETN) - Induction Period

Number of subjects included in analysis

526

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

sPGA Statistical Analysis 2

Comparison groups

Placebo - Induction Period v Ixe Q4W - Induction Period

Number of subjects included in analysis

515

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

sPGA Statistical Analysis 3

Comparison groups

Placebo - Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

519

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

Primary: Percentage of Participants achieving Psoriasis Area and Severity Index (PASI) ≥75% (PASI75) Improvement (Efficacy of ixekizumab in participants with moderate to severe chronic plaque psoriasis. Measure: Psoriasis Area and Severity Index [PASI])

Top of page

End point title

Percentage of Participants achieving Psoriasis Area and Severity Index (PASI) ≥75% (PASI75) Improvement (Efficacy of ixekizumab in participants with moderate to severe chronic plaque psoriasis. Measure: Psoriasis Area and Severity Index [PASI])

End point description

The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs). For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region * area score * weighing factor (head [0.1], upper limbs [0.2], trunk [0.3], lower limbs [0.4]). Overall scores range from 0 (no Ps) to 72 (the most severe disease). Participants achieving PASI75 were defined as having an improvement of ≥75% in the PASI score compared to baseline. Participants who did not meet the clinical response criteria or had missing data at Week 12 were considered non-responders for NRI analysis.

End point type

Primary

End point timeframe

Week 12

End point values	Placebo - Induction Period	50 mg Etanercept (ETN) - Induction Period	Ixe Q4W - Induction Period	Ixe Q2W - Induction Period
Number of subjects analysed	168 ^[5]	358 ^[6]	347 ^[7]	351 ^[8]
Units: percentage of participants
number (not applicable)	2.4	41.6	77.5	89.7

Notes
[5] - All randomized participants.
[6] - All randomized participants.
[7] - All randomized participants.
[8] - All randomized participants.

PASI75 Statistical Analysis 1

Comparison groups

50 mg Etanercept (ETN) - Induction Period v Placebo - Induction Period

Number of subjects included in analysis

526

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

PASI75 Statistical Analysis 2

Comparison groups

Placebo - Induction Period v Ixe Q4W - Induction Period

Number of subjects included in analysis

515

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

PASI75 Statistical Analysis 3

Comparison groups

Placebo - Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

519

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

Secondary: Percentage of Participants Achieving an sPGA (0) (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: [sPGA])

Top of page

End point title

Percentage of Participants Achieving an sPGA (0) (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: [sPGA])

End point description

The sPGA is the physician's determination of the participant's Ps lesions overall at a given time point. Lesions were categorized by descriptions for induration, erythema, and scaling. Participant’s Ps was assessed as 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), or 5 (very severe). Participants who did not meet the clinical response criteria or had missing data at Week 12 were considered non-responders for NRI analysis.

End point type

Secondary

End point timeframe

Week 12

End point values	Placebo - Induction Period	50 mg Etanercept (ETN) - Induction Period	Ixe Q4W - Induction Period	Ixe Q2W - Induction Period
Number of subjects analysed	168 ^[9]	358 ^[10]	347 ^[11]	351 ^[12]
Units: percentage of participants
number (not applicable)	0.6	5.9	32.3	41.9

Notes
[9] - All randomized participants.
[10] - All randomized participants.
[11] - All randomized participants.
[12] - All randomized participants.

sPGA (0) Statistical Analysis 1

Comparison groups

Placebo - Induction Period v 50 mg Etanercept (ETN) - Induction Period

Number of subjects included in analysis

526

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.005

Method

Cochran-Mantel-Haenszel

Confidence interval

sPGA (0) Statistical Analysis 2

Comparison groups

Placebo - Induction Period v Ixe Q4W - Induction Period

Number of subjects included in analysis

515

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

sPGA (0) Statistical Analysis 3

Comparison groups

Placebo - Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

519

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

Secondary: Percentage of Participants Achieving PASI 90% (PASI90) (Efficacy of ixekizumab in participants with moderate to severe chronic plaque psoriasis. Measure: [PASI])

Top of page

End point title

Percentage of Participants Achieving PASI 90% (PASI90) (Efficacy of ixekizumab in participants with moderate to severe chronic plaque psoriasis. Measure: [PASI])

End point description

The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs). For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored by itself and the scores were then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region * area score * weighing factor (head [0.1], upper limbs [0.2], trunk [0.3], lower limbs [0.4]). Overall scores range from 0 (no Ps) to 72 (the most severe disease). Participants achieving PASI90 were defined as having an improvement of ≥90% in the PASI score compared to baseline. Participants who did not meet the clinical response criteria or had missing data at Week 12 were considered non-responders for NRI analysis.

End point type

Secondary

End point timeframe

Week 12

End point values	Placebo - Induction Period	50 mg Etanercept (ETN) - Induction Period	Ixe Q4W - Induction Period	Ixe Q2W - Induction Period
Number of subjects analysed	168 ^[13]	358 ^[14]	347 ^[15]	351 ^[16]
Units: percentage of participants
number (not applicable)	0.6	18.7	59.7	70.7

Notes
[13] - All randomized participants.
[14] - All randomized participants.
[15] - All randomized participants.
[16] - All randomized participants.

PASI90 Statistical Analysis 1

Comparison groups

Placebo - Induction Period v 50 mg Etanercept (ETN) - Induction Period

Number of subjects included in analysis

526

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

PASI90 Statistical Analysis 2

Comparison groups

Placebo - Induction Period v Ixe Q4W - Induction Period

Number of subjects included in analysis

515

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

PASI90 Statistical Analysis 3

Comparison groups

Placebo - Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

519

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

Secondary: Percentage of Participants Achieving PASI 100% (PASI100)

Top of page

End point title

Percentage of Participants Achieving PASI 100% (PASI100)

End point description

The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs). For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored by itself and the scores were then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region * area score * weighing factor (head [0.1], upper limbs [0.2], trunk [0.3], lower limbs [0.4]). Overall scores range from 0 (no Ps) to 72 (the most severe disease). Participants achieving PASI100 were defined as having an improvement of 100% in the PASI score compared to baseline. Participants who did not meet the clinical response criteria or had missing data at Week 12 were considered non-responders for NRI analysis.

End point type

Secondary

End point timeframe

Week 12

End point values	Placebo - Induction Period	50 mg Etanercept (ETN) - Induction Period	Ixe Q4W - Induction Period	Ixe Q2W - Induction Period
Number of subjects analysed	168 ^[17]	358 ^[18]	347 ^[19]	351 ^[20]
Units: percentage of participants
number (not applicable)	0.6	5.3	30.8	40.5

Notes
[17] - All randomized participants.
[18] - All randomized participants.
[19] - All randomized participants.
[20] - All randomized participants.

PASI100 Statistical Analysis 1

Comparison groups

50 mg Etanercept (ETN) - Induction Period v Placebo - Induction Period

Number of subjects included in analysis

526

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.008

Method

Cochran-Mantel-Haenszel

Confidence interval

PASI100 Statistical Analysis 2

Comparison groups

Placebo - Induction Period v Ixe Q4W - Induction Period

Number of subjects included in analysis

515

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

PASI100 Statistical Analysis 3

Comparison groups

Placebo - Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

519

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

Secondary: Percentage of Participants Maintaining an sPGA (0,1) from Week 12 after Re-randomization at start of Maintenance Dosing Period to Week 60

Top of page

End point title

Percentage of Participants Maintaining an sPGA (0,1) from Week 12 after Re-randomization at start of Maintenance Dosing Period to Week 60

End point description

The sPGA is the physician's determination of the participant's Ps lesions overall at a given time point. Lesions were categorized by descriptions for induration, erythema, and scaling. Participant's Ps was assessed as 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), or 5 (very severe). Participants who did not meet the clinical response criteria or had missing data at Week 12 were considered non-responders for NRI analysis.

End point type

Secondary

End point timeframe

Week 60

End point values	Ixe/Placebo- Maintenance Period Primary Population (Pop)	Ixe/Ixe Q4W - Maintenance Period Primary Pop	Ixe/Ixe Q12W - Maintenance Period Primary Pop
Number of subjects analysed	176 ^[21]	187 ^[22]	181 ^[23]
Units: Percentage of participants
number (not applicable)	6.3	74.9	40.9

Notes
[21] - All randomized participants who had sPGA score of (0,1), re-randomized, and received drug.
[22] - All randomized participants who had sPGA score of (0,1), re-randomized, and received drug.
[23] - All randomized participants who had sPGA score of (0,1), re-randomized, and received drug.

sPGA (0,1) Statistical Analysis 1

Comparison groups

Ixe/Ixe Q12W - Maintenance Period Primary Pop v Ixe/Placebo- Maintenance Period Primary Population (Pop)

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Fisher exact

Confidence interval

sPGA (0,1) Statistical Analysis 2

Comparison groups

Ixe/Placebo- Maintenance Period Primary Population (Pop) v Ixe/Ixe Q4W - Maintenance Period Primary Pop

Number of subjects included in analysis

363

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Fisher exact

Confidence interval

Secondary: Percentage of Participants with Itching Severity (Itch Numeric Rating Scale [NRI]) Score ≥4 Point Reduction from Baseline

Top of page

End point title

Percentage of Participants with Itching Severity (Itch Numeric Rating Scale [NRI]) Score ≥4 Point Reduction from Baseline

End point description

The Itch Numeric Rating Scale (NRS) is a participant-administered, 11-point horizontal scale anchored at 0 and 10, with 0 representing "no itch" and 10 representing "worst itch imaginable". The number and percentage of participants achieving an Itch NRS ≥4 point reduction from baseline were presented by treatment group for participants who had a baseline Itch NRS ≥4. Describes worst level of itching in past 24 hours. Participants who did not meet the clinical response criteria or had missing data at Week 12 were considered non-responders for NRI analysis.

End point type

Secondary

End point timeframe

Week 12

End point values	Placebo - Induction Period	50 mg Etanercept (ETN) - Induction Period	Ixe Q4W - Induction Period	Ixe Q2W - Induction Period
Number of subjects analysed	135 ^[24]	306 ^[25]	293 ^[26]	303 ^[27]
Units: percentage of participants
number (not applicable)	14.1	57.8	76.8	85.1

Notes
[24] - All randomized participants who had Itch NRS ≥4 at baseline.
[25] - All randomized participants who had Itch NRS ≥4 at baseline.
[26] - All randomized participants who had Itch NRS ≥4 at baseline.
[27] - All randomized participants who had Itch NRS ≥4 at baseline.

Itch NRI Score Statistical Analysis 1

Comparison groups

Placebo - Induction Period v 50 mg Etanercept (ETN) - Induction Period

Number of subjects included in analysis

441

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

Itch NRI Score Statistical Analysis 2

Comparison groups

Placebo - Induction Period v Ixe Q4W - Induction Period

Number of subjects included in analysis

428

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

Itch NRI Score Statistical Analysis 3

Comparison groups

Placebo - Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

438

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

Secondary: Change from baseline in Dermatology-Specific Quality of Life Index (DLQI) Total Score (Quality of Life and Outcome Assessments. Measures: Participant Reported Outcomes [PRO])

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End point title

Change from baseline in Dermatology-Specific Quality of Life Index (DLQI) Total Score (Quality of Life and Outcome Assessments. Measures: Participant Reported Outcomes [PRO])

End point description

DLQI is a participant-administered, 10-question, validated, quality-of-life questionnaire that covers 6 domains, including symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories include 0 (not at all), 1 (a little), 2 (a lot), and 3 (very much); and "not relevant" and unanswered responses were scored as "0." Total scores range from 0 to 30, with higher score indicating greater quality of life impairment. A 5-point change from baseline is considered clinically relevant. Least Squares (LS) Mean change from baseline was calculated using mixed model repeated measures (MMRM) with baseline score as covariate, treatment, pooled center, visit and treatment-by-visit interaction as fixed effects.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo - Induction Period	50 mg Etanercept (ETN) - Induction Period	Ixe Q4W - Induction Period	Ixe Q2W - Induction Period
Number of subjects analysed	160 ^[28]	346 ^[29]	338 ^[30]	343 ^[31]
Units: units on a scale
least squares mean (standard error)	-2.0 ± 0.36	-7.7 ± 0.25	-9.4 ± 0.25	-10.4 ± 0.25

Notes
[28] - All randomized participants who had baseline and at least 1 post-baseline DLQI measurement.
[29] - All randomized participants who had baseline and at least 1 post-baseline DLQI measurement.
[30] - All randomized participants who had baseline and at least 1 post-baseline DLQI measurement.
[31] - All randomized participants who had baseline and at least 1 post-baseline DLQI measurement.

DLQI Statistical Analysis 1

Comparison groups

Placebo - Induction Period v 50 mg Etanercept (ETN) - Induction Period

Number of subjects included in analysis

506

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Confidence interval

DLQI Statistical Analysis 2

Comparison groups

Placebo - Induction Period v Ixe Q4W - Induction Period

Number of subjects included in analysis

498

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Confidence interval

DLQI Statistical Analysis 3

Comparison groups

Placebo - Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

503

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Confidence interval

Secondary: Change from Baseline in Nail Psoriasis Severity Index (NAPSI)

Top of page

End point title

Change from Baseline in Nail Psoriasis Severity Index (NAPSI)

End point description

The NAPSI scale is used to evaluate the severity of fingernail bed Ps and fingernail matrix Ps. The fingernail bed and fingernail matrix are each divided into quadrants. Each fingernail is given a score for fingernail bed Ps and fingernail matrix Ps, each with scores of 0 (none) to 4 (Ps in all 4 quadrants), depending on the presence (score of 1) or absence (score of 0) of Ps in each quadrant of the fingernail bed or matrix. The NAPSI score of a fingernail is the sum of scores from each quadrant of the fingernail bed and fingernail matrix (maximum of 8). The total NAPSI score equals the sum of all fingernails and ranges from 0 to 80 with higher scores indicating more severe Ps. LS mean change from baseline in NAPSI score was calculated using MMRM with baseline score as covariate, treatment, pooled center, visit and treatment-by-visit interaction as fixed effects.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo - Induction Period	50 mg Etanercept (ETN) - Induction Period	Ixe Q4W - Induction Period	Ixe Q2W - Induction Period
Number of subjects analysed	111 ^[32]	219 ^[33]	215 ^[34]	206 ^[35]
Units: units on a scale
least squares mean (standard error)	-0.82 ± 1.162	-5.34 ± 0.835	-7.39 ± 0.843	-8.60 ± 0.853

Notes
[32] - All randomized participants with fingernail Ps involvement at baseline and had ≥1 post-baseline.
[33] - All randomized participants with fingernail Ps involvement at baseline and had ≥1 post-baseline.
[34] - All randomized participants with fingernail Ps involvement at baseline and had ≥1 post-baseline.
[35] - All randomized participants with fingernail Ps involvement at baseline and had ≥1 post-baseline.

NAPSI Statistical Analysis 1

Comparison groups

Placebo - Induction Period v 50 mg Etanercept (ETN) - Induction Period

Number of subjects included in analysis

330

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

Mixed models analysis

Confidence interval

NAPSI Statistical Analysis 2

Comparison groups

Placebo - Induction Period v Ixe Q4W - Induction Period

Number of subjects included in analysis

326

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Confidence interval

NAPSI Statistical Analysis 3

Comparison groups

Placebo - Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

317

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Confidence interval

Secondary: Change from Baseline Psoriasis Scalp Severity Index (PSSI) Score

Top of page

End point title

Change from Baseline Psoriasis Scalp Severity Index (PSSI) Score

End point description

The PSSI is a physician assessment of erythema, induration and desquamation and percent of scalp that is covered with a scores range from 0 (none) to 4 (very severe). The composite score is derived from the sum of scores for erythema, induration, and desquamation multiplied by the score recorded for the extent of the scalp area involved, 1 (<10%) to 6 (90%-100%) with a total scores range from 0 (less severity) to 72 (more severity), with lower scores indicating less severity. LS mean change from baseline in PSSI score was calculated using MMRM with baseline score as a covariate, treatment, pooled center, visit, and treatment-by-visit interaction as fixed effects. Missing data was imputed by last observation carried forward (LOCF).

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo - Induction Period	50 mg Etanercept (ETN) - Induction Period	Ixe Q4W - Induction Period	Ixe Q2W - Induction Period
Number of subjects analysed	150 ^[36]	316 ^[37]	307 ^[38]	318 ^[39]
Units: units on a scale
least squares mean (standard error)	-3.8 ± 0.73	-14.8 ± 0.50	-18.5 ± 0.51	-18.7 ± 0.50

Notes
[36] - All randomized participants with scalp Ps involvement at baseline and had at least 1 post-baseline.
[37] - All randomized participants with scalp Ps involvement at baseline and had at least 1 post-baseline.
[38] - All randomized participants with scalp Ps involvement at baseline and had at least 1 post-baseline.
[39] - All randomized participants with scalp Ps involvement at baseline and had at least 1 post-baseline.

PSSI Statistical Analysis 1

Comparison groups

Placebo - Induction Period v 50 mg Etanercept (ETN) - Induction Period

Number of subjects included in analysis

466

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Confidence interval

PSSI Statistical Analysis 2

Comparison groups

Placebo - Induction Period v Ixe Q4W - Induction Period

Number of subjects included in analysis

457

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Confidence interval

PSSI Statistical Analysis 3

Comparison groups

Placebo - Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

468

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Confidence interval

Secondary: Change from Baseline in Percent of Body Surface Area (BSA) involvement of psoriasis

Top of page

End point title

Change from Baseline in Percent of Body Surface Area (BSA) involvement of psoriasis

End point description

The percentage involvement of psoriasis on each participant's body surface area was assessed by the investigator on a continuous scale from 0% (no involvement) to 100% (full involvement), in which 1% corresponds to the size of the participant's hand including palm, fingers and thumb. LS mean change from baseline in BSA was calculated using MMRM with baseline BSA as a covariate, treatment, pooled center, visit, and treatment-by-visit interaction as fixed effects.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo - Induction Period	50 mg Etanercept (ETN) - Induction Period	Ixe Q4W - Induction Period	Ixe Q2W - Induction Period
Number of subjects analysed	166 ^[40]	350 ^[41]	342 ^[42]	348 ^[43]
Units: units on a scale
least squares mean (standard error)	0.5 ± 1.05	-12.4 ± 0.72	-20.3 ± 0.72	-20.6 ± 0.71

Notes
[40] - All randomized participants who had at least 1 post-baseline BSA measurement.
[41] - All randomized participants who had at least 1 post-baseline BSA measurement.
[42] - All randomized participants who had at least 1 post-baseline BSA measurement.
[43] - All randomized participants who had at least 1 post-baseline BSA measurement.

BSA Statistical Analysis 1

Comparison groups

Placebo - Induction Period v 50 mg Etanercept (ETN) - Induction Period

Number of subjects included in analysis

516

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Confidence interval

BSA Statistical Analysis 2

Comparison groups

Placebo - Induction Period v Ixe Q4W - Induction Period

Number of subjects included in analysis

508

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Confidence interval

BSA Statistical Analysis 3

Comparison groups

Placebo - Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

514

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Confidence interval

Secondary: Change from baseline in Quick Inventory of Depressive Symptomatology-Self Report 16 items (QIDS-SR16) Total Score

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End point title

Change from baseline in Quick Inventory of Depressive Symptomatology-Self Report 16 items (QIDS-SR16) Total Score

End point description

The QIDS-SR16 is a self-administered, 16-item instrument in which a participant is asked to consider each statement as it relates to the way they have felt for the past 7 days. There is a 4-point scale for each item ranging from 0 (best) to 3 (worst). The 16 items are scored to give 9 individual depression domains (sad mood, concentration, self-criticism, suicidal ideation, interest, energy/fatigue, sleep disturbance [initial, middle and late insomnia or hypersomnia], decrease/increase in appetite/weight, and psychomotor agitation/retardation), which are summed to give a single score ranging from 0 to 27, with higher scores denoting greater symptom severity. LS mean change from baseline in total QIDS-SR16 score was calculated using the analysis of covariance (ANCOVA) model with treatment, pooled center and baseline QIDS total score. Missing data was imputed by last observation carried forward (LOCF).

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo - Induction Period	50 mg Etanercept (ETN) - Induction Period	Ixe Q4W - Induction Period	Ixe Q2W - Induction Period
Number of subjects analysed	162 ^[44]	342 ^[45]	334 ^[46]	347 ^[47]
Units: units on a scale
least squares mean (standard error)	0.1 ± 0.21	-0.3 ± 0.15	-0.7 ± 0.15	-0.9 ± 0.15

Notes
[44] - All randomized participants who had baseline and at least 1 post baseline QIDS-SR16 measurement
[45] - All randomized participants who had baseline and at least 1 post baseline QIDS-SR16 measurement
[46] - All randomized participants who had baseline and at least 1 post baseline QIDS-SR16 measurement
[47] - All randomized participants who had baseline and at least 1 post baseline QIDS-SR16 measurement

QIDS-SR16 Statistical Analysis 1

Comparison groups

Placebo - Induction Period v 50 mg Etanercept (ETN) - Induction Period

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.15

Method

ANCOVA

Confidence interval

QIDS-SR16 Statistical Analysis 2

Comparison groups

Placebo - Induction Period v Ixe Q4W - Induction Period

Number of subjects included in analysis

496

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

ANCOVA

Confidence interval

QIDS-SR16 Statistical Analysis 3

Comparison groups

Placebo - Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

509

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Confidence interval

Secondary: Change from Baseline in Absenteeism of Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO)

Top of page

End point title

Change from Baseline in Absenteeism of Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO)

End point description

The (WPAI-PSO) is a 6-item instrument used to assess the impact of psoriasis on productivity impairment within the past 7 days and has four domains, namely, absenteeism, presenteeism (reduced productivity while at work), an overall work impairment score, and impairment in daily activities performed outside of work. Four scores are derived as percentages: absenteeism, presenteeism, overall work impairment (absenteeism and presenteeism), and impairment in activities performed outside of work. Percentage is calculated as each score * 100 and ranges from 0 to 100; greater scores indicate greater impairment. LS mean change from baseline in each WPAI-PSO score was calculated using the (ANCOVA) model with treatment, pooled center and baseline WPAI value. Missing data was imputed by last observation carried forward ( LOCF ).

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo - Induction Period	50 mg Etanercept (ETN) - Induction Period	Ixe Q4W - Induction Period	Ixe Q2W - Induction Period
Number of subjects analysed	87 ^[48]	199 ^[49]	204 ^[50]	213 ^[51]
Units: units on a scale
least squares mean (standard error)
Absenteeism	-1.5 ± 0.83	-3.7 ± 0.55	-3.2 ± 0.54	-3.9 ± 0.54

Notes
[48] - All randomized participants who had baseline and at least 1 post baseline WPAI-PSO Absenteeism.
[49] - All randomized participants who had baseline and at least 1 post baseline WPAI-PSO Absenteeism.
[50] - All randomized participants who had baseline and at least 1 post baseline WPAI-PSO Absenteeism.
[51] - All randomized participants who had baseline and at least 1 post baseline WPAI-PSO Absenteeism.

WPAI-PSO Statistical Analysis 1

Statistical analysis description

Absenteeism Score

Comparison groups

Placebo - Induction Period v 50 mg Etanercept (ETN) - Induction Period

Number of subjects included in analysis

286

Analysis specification

Pre-specified

Analysis type

superiority ^[52]

P-value

= 0.026

Method

ANCOVA

Confidence interval

Notes
[52] - Absenteeism Score

WPAI-PSO Statistical Analysis 2

Statistical analysis description

Absenteeism Score

Comparison groups

Placebo - Induction Period v Ixe Q4W - Induction Period

Number of subjects included in analysis

291

Analysis specification

Pre-specified

Analysis type

superiority ^[53]

P-value

= 0.076

Method

ANCOVA

Confidence interval

Notes
[53] - Absenteeism Score

WPAI-PSO Statistical Analysis 3

Statistical analysis description

Absenteeism Score

Comparison groups

Placebo - Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

300

Analysis specification

Pre-specified

Analysis type

superiority ^[54]

P-value

= 0.016

Method

ANCOVA

Confidence interval

Notes
[54] - Absenteeism Score

Secondary: Change From Baseline in Activity Impairment Score of WPAI-PSO

Top of page

End point title

Change From Baseline in Activity Impairment Score of WPAI-PSO

End point description

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo - Induction Period	50 mg Etanercept (ETN) - Induction Period	Ixe Q4W - Induction Period	Ixe Q2W - Induction Period
Number of subjects analysed	160 ^[55]	342 ^[56]	332 ^[57]	340 ^[58]
Units: units on a scale
least squares mean (standard deviation)
Activity Impairment Score	-0.4 ± 1.46	-16.6 ± 1.00	-22.6 ± 1.02	-25.8 ± 1.01

Notes
[55] - All randomized participants who had baseline and at least 1 post baseline activity impairment score.
[56] - All randomized participants who had baseline and at least 1 post baseline activity impairment score.
[57] - All randomized participants who had baseline and at least 1 post baseline activity impairment score.
[58] - All randomized participants who had baseline and at least 1 post baseline activity impairment score.

WPAI-PSO Statistical Analysis 4

Comparison groups

Placebo - Induction Period v 50 mg Etanercept (ETN) - Induction Period

Number of subjects included in analysis

502

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Confidence interval

WPAI-PSO Statistical Analysis 5

Comparison groups

Placebo - Induction Period v Ixe Q4W - Induction Period

Number of subjects included in analysis

492

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Confidence interval

WPAI-PSO Statistical Analysis 6

Comparison groups

Placebo - Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

500

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Confidence interval

Secondary: Change From Baseline in Presenteeism Score of WPAI-PSO

Top of page

End point title

Change From Baseline in Presenteeism Score of WPAI-PSO

End point description

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo - Induction Period	50 mg Etanercept (ETN) - Induction Period	Ixe Q4W - Induction Period	Ixe Q2W - Induction Period
Number of subjects analysed	94 ^[59]	217 ^[60]	226 ^[61]	232 ^[62]
Units: units on a scale
least squares mean (standard deviation)
Presenteeism Score	-2.4 ± 1.59	-12.4 ± 1.05	-18.5 ± 1.03	-18.2 ± 1.03

Notes
[59] - All randomized participants who had baseline and at least 1 post baseline presenteeism measurement.
[60] - All randomized participants who had baseline and at least 1 post baseline presenteeism measurement.
[61] - All randomized participants who had baseline and at least 1 post baseline presenteeism measurement.
[62] - All randomized participants who had baseline and at least 1 post baseline presenteeism measurement

WPAI-PSO Statistical Analysis 7

Comparison groups

50 mg Etanercept (ETN) - Induction Period v Placebo - Induction Period

Number of subjects included in analysis

311

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Confidence interval

WPAI-PSO Statistical Analysis 8

Comparison groups

Placebo - Induction Period v Ixe Q4W - Induction Period

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Confidence interval

WPAI PSO Statistical Analysis 9

Comparison groups

Placebo - Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

326

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Confidence interval

Secondary: Change From Baseline in Work Productivity Loss Score of WPAI-PSO

Top of page

End point title

Change From Baseline in Work Productivity Loss Score of WPAI-PSO

End point description

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo - Induction Period	50 mg Etanercept (ETN) - Induction Period	Ixe Q4W - Induction Period	Ixe Q2W - Induction Period
Number of subjects analysed	86 ^[63]	199 ^[64]	203 ^[65]	211 ^[66]
Units: unit on scale
least squares mean (standard deviation)
Work Productivity Loss Score	-2.0 ± 1.80	-13.7 ± 1.18	-19.3 ± 1.18	-19.5 ± 1.18

Notes
[63] - All randomized participants who had baseline and at least 1 post baseline work productivity score.
[64] - All randomized participants who had baseline and at least 1 post baseline work productivity score.
[65] - All randomized participants who had baseline and at least 1 post baseline work productivity score.
[66] - All randomized participants who had baseline and at least 1 post baseline work productivity score.

WPAI-PSO Statistical Analysis 10

Comparison groups

Placebo - Induction Period v 50 mg Etanercept (ETN) - Induction Period

Number of subjects included in analysis

285

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Confidence interval

WPAI-PSO Statistical Analysis 11

Comparison groups

Placebo - Induction Period v Ixe Q4W - Induction Period

Number of subjects included in analysis

289

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Confidence interval

WPAI-PSO Statistical Analysis 12

Comparison groups

Placebo - Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

297

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Confidence interval

Secondary: Change from baseline in Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) and Physical Component Summary (PCS) and Mental Component Summary (MCS

Top of page

End point title

Change from baseline in Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) and Physical Component Summary (PCS) and Mental Component Summary (MCS

End point description

The SF-36 is a participant-reported outcome measure evaluating participant's health status. It comprises 36 items covering 8 domains: physical functioning, role physical, role emotional, bodily pain, vitality, social functioning, mental health, and general health. Items are answered on Likert scales of varying lengths. The 8 domains are regrouped into the PCS and MCS scores. The summary scores range from 0 to 100, with higher scores indicating better levels of function and/or better health. In this study, the SF- 36 acute version was used, which has a 1 week recall period. LS mean change from baseline in SF-36 score was calculated using the ANCOVA model with treatment, pooled center and baseline SF-36 score. Missing data was imputed by last observation carried forward ( LOCF ).

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo - Induction Period	50 mg Etanercept (ETN) - Induction Period	Ixe Q4W - Induction Period	Ixe Q2W - Induction Period
Number of subjects analysed	158 ^[67]	336 ^[68]	333 ^[69]	344 ^[70]
Units: units on a scale
least squares mean (standard error)
Physical Summary Score	-0.4495 ± 0.5226	2.5498 ± 0.3610	4.5726 ± 0.3628	3.7964 ± 0.3575
Mental Summary Score	-0.0955 ± 0.5886	2.3221 ± 0.4065	2.8504 ± 0.4090	4.5142 ± 0.4026

Notes
[67] - All randomized participants who had baseline and at least 1 post baseline SF-36 measurement.
[68] - All randomized participants who had baseline and at least 1 post baseline SF-36 measurement.
[69] - All randomized participants who had baseline and at least 1 post baseline SF-36 measurement.
[70] - All randomized participants who had baseline and at least 1 post baseline SF-36 measurement.

SF-36 Statistical Analysis 1

Statistical analysis description

Physical Summary Score

Comparison groups

Placebo - Induction Period v 50 mg Etanercept (ETN) - Induction Period

Number of subjects included in analysis

494

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Confidence interval

SF-36 Statistical Analysis 2

Statistical analysis description

Physical Summary Score

Comparison groups

Placebo - Induction Period v Ixe Q4W - Induction Period

Number of subjects included in analysis

491

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Confidence interval

SF-36 Statistical Analysis 3

Statistical analysis description

Physical Summary Score

Comparison groups

Placebo - Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

502

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.01

Method

ANCOVA

Confidence interval

SF-36 Statistical Analysis 4

Statistical analysis description

Mental Summary Score

Comparison groups

Placebo - Induction Period v 50 mg Etanercept (ETN) - Induction Period

Number of subjects included in analysis

494

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Confidence interval

SF-36 Statistical Analysis 5

Statistical analysis description

Mental Summary Score

Comparison groups

Placebo - Induction Period v Ixe Q4W - Induction Period

Number of subjects included in analysis

491

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Confidence interval

SF-36 Statistical Analysis 6

Statistical analysis description

Mental Summary Score

Comparison groups

Placebo - Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

502

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Confidence interval

Secondary: Change from baseline in Patient's Global Assessment (PatGA) of Disease Severity

Top of page

End point title

Change from baseline in Patient's Global Assessment (PatGA) of Disease Severity

End point description

The Patient's Global Assessment of Disease Severity is a single-item patient reported outcome measure on which participants are asked to rate by circling a number on a 0 to 5 NRS the severity of their psoriasis "today" from 0 (Clear) = no psoriasis to 5 (Severe) = the worst their psoriasis has ever been. LS mean change from baseline in patient's global assessment of disease severity score was calculated using (MMRM) with baseline score as a covariate, treatment, pooled center, visit, and treatment-by-visit interaction as fixed effects.

End point type

Secondary

End point timeframe

Baseline, 12 Weeks

End point values	Placebo - Induction Period	50 mg Etanercept (ETN) - Induction Period	Ixe Q4W - Induction Period	Ixe Q2W - Induction Period
Number of subjects analysed	164 ^[71]	348 ^[72]	339 ^[73]	343 ^[74]
Units: units on a scale
least squares mean (standard error)	-0.4 ± 0.09	-2.1 ± 0.06	-3.0 ± 0.06	-3.2 ± 0.06

Notes
[71] - All randomized participants who had baseline and at least 1 post baseline PatGA measurement.
[72] - All randomized participants who had baseline and at least 1 post baseline PatGA measurement.
[73] - All randomized participants who had baseline and at least 1 post baseline PatGA measurement.
[74] - All randomized participants who had baseline and at least 1 post baseline PatGA measurement.

PatGA Statistical Analysis 1

Comparison groups

Placebo - Induction Period v 50 mg Etanercept (ETN) - Induction Period

Number of subjects included in analysis

512

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Confidence interval

PatGA Statistical Analysis 2

Comparison groups

Placebo - Induction Period v Ixe Q4W - Induction Period

Number of subjects included in analysis

503

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Confidence interval

PatGA Statistical Analysis 3

Comparison groups

Placebo - Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

507

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Confidence interval

Secondary: Percentage of Participants achieving Palmoplantar PASI (PPASI) of of ≥50% (PPASI50), ≥75% (PPASI75) or 100% (PPASI100)

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End point title

Percentage of Participants achieving Palmoplantar PASI (PPASI) of of ≥50% (PPASI50), ≥75% (PPASI75) or 100% (PPASI100)

End point description

The Palmoplantar PASI is a composite score derived from the sum scores for erythema, induration, and desquamation multiplied by a score for the extent of palm and sole area involvement, ranging from 0 to 72. The PPASI was only assessed if participants have palmoplantar psoriasis at baseline. Participants achieving PPASI50, PPASI75 or PASI100 were defined as having an improvement of at least 50%, 75%, or of 100%, respectively, in the PPASI scores compared to baseline. Participants who did not meet clinical response criteria or have missing data will be considered non-responders.

End point type

Secondary

End point timeframe

Week 12

End point values	Placebo - Induction Period	50 mg Etanercept (ETN) - Induction Period	Ixe Q4W - Induction Period	Ixe Q2W - Induction Period
Number of subjects analysed	55 ^[75]	95 ^[76]	102 ^[77]	104 ^[78]
Units: percentage of participants
number (not applicable)
PPASI 50	43.6	71.6	85.3	88.5
PPASI 75	30.9	61.1	80.4	79.8
PPASI 100	25.5	50.5	69.6	71.2

Notes
[75] - All randomized participants who had palmoplantar Ps involvement at baseline.
[76] - All randomized participants who had palmoplantar Ps involvement at baseline.
[77] - All randomized participants who had palmoplantar Ps involvement at baseline.
[78] - All randomized participants who had palmoplantar Ps involvement at baseline.

PPASI 50 Statistical Analysis 1

Comparison groups

Placebo - Induction Period v 50 mg Etanercept (ETN) - Induction Period

Number of subjects included in analysis

150

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

PPASI 50 Statistical Analysis 2

Comparison groups

Placebo - Induction Period v Ixe Q4W - Induction Period

Number of subjects included in analysis

157

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

PPASI 50 Statistical Analysis 3

Comparison groups

Placebo - Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

PPASI 75 Statistical Analysis 4

Comparison groups

Placebo - Induction Period v 50 mg Etanercept (ETN) - Induction Period

Number of subjects included in analysis

150

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

PPASI 75 Statistical Analysis 5

Comparison groups

Placebo - Induction Period v Ixe Q4W - Induction Period

Number of subjects included in analysis

157

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

PPASI 75 Statistical Analysis 6

Comparison groups

Placebo - Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

PPASI 100 Statistical Analysis 7

Comparison groups

Placebo - Induction Period v 50 mg Etanercept (ETN) - Induction Period

Number of subjects included in analysis

150

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

Cochran-Mantel-Haenszel

Confidence interval

PPASI 100 Statistical Analysis 8

Comparison groups

Placebo - Induction Period v Ixe Q4W - Induction Period

Number of subjects included in analysis

157

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

PPASI 100 Statistical Analysis 9

Comparison groups

Placebo - Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

Secondary: Percentage of participants with Anti-Ixekizumab Antibodies

Top of page

End point title

Percentage of participants with Anti-Ixekizumab Antibodies

End point description

Percentage of participants with treatment-emergent positive anti-ixekizumab antibodies was summarized by treatment group. Percentage was calculated based on the # of evaluable participants and was calculated by number of participants with treatment-emergent positive anti-ixekizumab antibodies / number of evaluable participants * 100%.

End point type

Secondary

End point timeframe

Baseline to Week 12

End point values	Placebo - Induction Period	50 mg Etanercept (ETN) - Induction Period	Ixe Q4W - Induction Period	Ixe Q2W - Induction Period
Number of subjects analysed	165 ^[79]	347 ^[80]	340 ^[81]	346 ^[82]
Units: Percentage of Participants
number (not applicable)	0	2.9	14.1	10.4

Notes
[79] - All randomized participants who received at least 1 dose of study treatment and had evaluable data.
[80] - All randomized participants who received at least 1 dose of study treatment and had evaluable data.
[81] - All randomized participants who received at least 1 dose of study treatment and had evaluable data.
[82] - All randomized participants who received at least 1 dose of study treatment and had evaluable data.

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Induction, Maintenance Dosing, Long Term Extension and Follow-Up Periods

Adverse event reporting additional description

I1F-MC-RHBA

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

22.0

Reporting group title

Placebo - Induction period

Reporting group description

Reporting group title

50 mg ETN - Induction Period

Reporting group description

Reporting group title

Ixe Q4W - Induction period

Reporting group description

Reporting group title

Ixe Q2W - Induction period

Reporting group description

Reporting group title

Ixe/Placebo - Maintenance Period Primary Population

Reporting group description

Reporting group title

Ixe/Ixe Q4W - Maintenance Period Primary Population

Reporting group description

Reporting group title

Ixe/Ixe Q12W - Maintenance Period Primary Population

Reporting group description

Reporting group title

Placebo Resp/Placebo - Maintenance Period Secondary Population

Reporting group description

Reporting group title

Placebo NonResp/Ixe Q4W - Maintenance Period Secondary Pop

Reporting group description

Reporting group title

ETNResp/Placebo - Maintenance Period Secondary Population

Reporting group description

Reporting group title

ETN NonResp/Ixe Q4W - Maintenance Period Secondary Population

Reporting group description

Reporting group title

Ixe Q4W NonResp/Ixe Q4W - Maintenance Period Secondary Pop

Reporting group description

Reporting group title

Ixe Q2W NonResp/Ixe Q4W - Maintenance Period Secondary Pop

Reporting group description

Reporting group title

Ixe Q4W - Maintenance Relapse Population

Reporting group description

Reporting group title

Placebo Long-Term Extension Period

Reporting group description

Reporting group title

Ixe Long-Term Extension Period

Reporting group description

Reporting group title

Total Ixe Long-Term Extension Period

Reporting group description

Reporting group title

Placebo Post-Treatment Follow-Up

Reporting group description

Reporting group title

ETN Post-Treatment Follow-Up

Reporting group description

Reporting group title

Ixe Q12W Post-Treatment Follow-Up

Reporting group description

Reporting group title

Ixe Q4W Post-Treatment Follow-Up

Reporting group description

Reporting group title

Ixe Q12W Post-Treatment Follow-Up

Reporting group description

Placebo - Induction period

50 mg ETN - Induction Period

Ixe Q4W - Induction period

Ixe Q2W - Induction period

Ixe/Placebo - Maintenance Period Primary Population

Ixe/Ixe Q4W - Maintenance Period Primary Population

Ixe/Ixe Q12W - Maintenance Period Primary Population

Placebo Resp/Placebo - Maintenance Period Secondary Population

Placebo NonResp/Ixe Q4W - Maintenance Period Secondary Pop

ETNResp/Placebo - Maintenance Period Secondary Population

ETN NonResp/Ixe Q4W - Maintenance Period Secondary Population

Ixe Q4W NonResp/Ixe Q4W - Maintenance Period Secondary Pop

Ixe Q2W NonResp/Ixe Q4W - Maintenance Period Secondary Pop

Ixe Q4W - Maintenance Relapse Population

Placebo Long-Term Extension Period

Ixe Long-Term Extension Period

Total Ixe Long-Term Extension Period

Placebo Post-Treatment Follow-Up

ETN Post-Treatment Follow-Up

Ixe Q12W Post-Treatment Follow-Up

Ixe Q4W Post-Treatment Follow-Up

Ixe Q12W Post-Treatment Follow-Up

Total subjects affected by serious adverse events

subjects affected / exposed

3 / 167 (1.80%)

8 / 357 (2.24%)

8 / 347 (2.31%)

5 / 350 (1.43%)

8 / 176 (4.55%)

12 / 187 (6.42%)

14 / 181 (7.73%)

0 / 3 (0.00%)

13 / 155 (8.39%)

2 / 132 (1.52%)

9 / 200 (4.50%)

4 / 75 (5.33%)

2 / 49 (4.08%)

14 / 368 (3.80%)

1 / 26 (3.85%)

107 / 979 (10.93%)

107 / 1002 (10.68%)

1 / 16 (6.25%)

0 / 6 (0.00%)

3 / 248 (1.21%)

12 / 656 (1.83%)

0 / 24 (0.00%)

number of deaths (all causes)

number of deaths resulting from adverse events

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

breast cancer

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

1 / 200 (0.50%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

breast neoplasm

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

1 / 656 (0.15%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cholesteatoma

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

colon adenoma

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

follicular thyroid cancer

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

invasive ductal breast carcinoma

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

1 / 656 (0.15%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

malignant melanoma

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

1 / 357 (0.28%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (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 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

1 / 176 (0.57%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pituitary tumour benign

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

prostate cancer

alternative dictionary used: MedDRA 22.0

subjects affected / exposed ^[1]

0 / 119 (0.00%)

0 / 235 (0.00%)

0 / 244 (0.00%)

0 / 221 (0.00%)

0 / 110 (0.00%)

1 / 131 (0.76%)

1 / 120 (0.83%)

0 / 1 (0.00%)

0 / 112 (0.00%)

0 / 89 (0.00%)

0 / 126 (0.00%)

0 / 53 (0.00%)

0 / 30 (0.00%)

0 / 239 (0.00%)

0 / 14 (0.00%)

3 / 666 (0.45%)

3 / 678 (0.44%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 170 (0.00%)

0 / 453 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

1 / 1

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

pyogenic granuloma

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

1 / 187 (0.53%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

renal cell carcinoma

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

1 / 656 (0.15%)

0 / 24 (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

small intestine adenocarcinoma

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

1 / 181 (0.55%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

transitional cell carcinoma

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

tumour embolism

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

1 / 656 (0.15%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

uterine leiomyoma

alternative dictionary used: MedDRA 22.0

subjects affected / exposed ^[2]

0 / 48 (0.00%)

0 / 122 (0.00%)

0 / 103 (0.00%)

0 / 129 (0.00%)

1 / 66 (1.52%)

0 / 56 (0.00%)

0 / 61 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 74 (0.00%)

0 / 22 (0.00%)

0 / 19 (0.00%)

0 / 129 (0.00%)

0 / 12 (0.00%)

0 / 313 (0.00%)

0 / 324 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 78 (0.00%)

0 / 203 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

aortic aneurysm

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

aortic dilatation

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

aortic stenosis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

1 / 181 (0.55%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

2 / 979 (0.20%)

2 / 1002 (0.20%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

circulatory collapse

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

1 / 656 (0.15%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

deep vein thrombosis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

1 / 368 (0.27%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

malignant hypertension

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

peripheral arterial occlusive disease

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

1 / 357 (0.28%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

peripheral artery stenosis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Surgical and medical procedures

coronary revascularisation

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

gallbladder operation

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

gastrectomy

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

uterine dilation and curettage

alternative dictionary used: MedDRA 22.0

subjects affected / exposed ^[3]

0 / 48 (0.00%)

0 / 122 (0.00%)

0 / 103 (0.00%)

0 / 129 (0.00%)

0 / 66 (0.00%)

0 / 56 (0.00%)

0 / 61 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 74 (0.00%)

0 / 22 (0.00%)

0 / 19 (0.00%)

0 / 129 (0.00%)

0 / 12 (0.00%)

0 / 313 (0.00%)

0 / 324 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

1 / 78 (1.28%)

0 / 203 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pregnancy, puerperium and perinatal conditions

abortion spontaneous

alternative dictionary used: MedDRA 22.0

subjects affected / exposed ^[4]

0 / 48 (0.00%)

0 / 122 (0.00%)

0 / 103 (0.00%)

0 / 129 (0.00%)

0 / 66 (0.00%)

0 / 56 (0.00%)

0 / 61 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 74 (0.00%)

0 / 22 (0.00%)

0 / 19 (0.00%)

1 / 129 (0.78%)

0 / 12 (0.00%)

1 / 313 (0.32%)

1 / 324 (0.31%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 78 (0.00%)

1 / 203 (0.49%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

imminent abortion

alternative dictionary used: MedDRA 22.0

subjects affected / exposed ^[5]

0 / 48 (0.00%)

0 / 122 (0.00%)

0 / 103 (0.00%)

0 / 129 (0.00%)

0 / 66 (0.00%)

0 / 56 (0.00%)

0 / 61 (0.00%)

0 / 2 (0.00%)

1 / 43 (2.33%)

0 / 43 (0.00%)

0 / 74 (0.00%)

0 / 22 (0.00%)

0 / 19 (0.00%)

0 / 129 (0.00%)

0 / 12 (0.00%)

0 / 313 (0.00%)

0 / 324 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 78 (0.00%)

0 / 203 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General disorders and administration site conditions

asthenia

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

death

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

2 / 979 (0.20%)

2 / 1002 (0.20%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 2

0 / 0

injection site reaction

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

1 / 357 (0.28%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

non-cardiac chest pain

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

1 / 187 (0.53%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

polyp

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pyrexia

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

1 / 368 (0.27%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Immune system disorders

anaphylactic reaction

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

1 / 155 (0.65%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

hypersensitivity

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

1 / 155 (0.65%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Reproductive system and breast disorders

acquired hydrocele

alternative dictionary used: MedDRA 22.0

subjects affected / exposed ^[6]

0 / 119 (0.00%)

0 / 235 (0.00%)

0 / 244 (0.00%)

0 / 221 (0.00%)

0 / 110 (0.00%)

0 / 131 (0.00%)

0 / 120 (0.00%)

0 / 1 (0.00%)

0 / 112 (0.00%)

0 / 89 (0.00%)

0 / 126 (0.00%)

0 / 53 (0.00%)

0 / 30 (0.00%)

0 / 239 (0.00%)

0 / 14 (0.00%)

1 / 666 (0.15%)

1 / 678 (0.15%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 170 (0.00%)

0 / 453 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

benign prostatic hyperplasia

alternative dictionary used: MedDRA 22.0

subjects affected / exposed ^[7]

0 / 119 (0.00%)

0 / 235 (0.00%)

0 / 244 (0.00%)

0 / 221 (0.00%)

0 / 110 (0.00%)

0 / 131 (0.00%)

0 / 120 (0.00%)

0 / 1 (0.00%)

0 / 112 (0.00%)

0 / 89 (0.00%)

0 / 126 (0.00%)

0 / 53 (0.00%)

0 / 30 (0.00%)

0 / 239 (0.00%)

0 / 14 (0.00%)

2 / 666 (0.30%)

2 / 678 (0.29%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 170 (0.00%)

0 / 453 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

penile dysplasia

alternative dictionary used: MedDRA 22.0

subjects affected / exposed ^[8]

0 / 119 (0.00%)

0 / 235 (0.00%)

0 / 244 (0.00%)

0 / 221 (0.00%)

0 / 110 (0.00%)

0 / 131 (0.00%)

0 / 120 (0.00%)

0 / 1 (0.00%)

0 / 112 (0.00%)

0 / 89 (0.00%)

0 / 126 (0.00%)

0 / 53 (0.00%)

0 / 30 (0.00%)

0 / 239 (0.00%)

0 / 14 (0.00%)

1 / 666 (0.15%)

1 / 678 (0.15%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 170 (0.00%)

0 / 453 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

acute respiratory failure

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

1 / 167 (0.60%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

asthma

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

chronic obstructive pulmonary disease

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

1 / 350 (0.29%)

0 / 176 (0.00%)

0 / 187 (0.00%)

1 / 181 (0.55%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

2 / 979 (0.20%)

2 / 1002 (0.20%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

dyspnoea

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

1 / 187 (0.53%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pleural effusion

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

2 / 979 (0.20%)

2 / 1002 (0.20%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

pneumothorax

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pulmonary embolism

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

1 / 368 (0.27%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (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

sinus disorder

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

1 / 26 (3.85%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

sleep apnoea syndrome

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

1 / 368 (0.27%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

tonsillar hypertrophy

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Psychiatric disorders

anxiety

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

depression

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

psychotic disorder

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

schizophrenia

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

suicide attempt

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

1 / 347 (0.29%)

1 / 350 (0.29%)

0 / 176 (0.00%)

0 / 187 (0.00%)

1 / 181 (0.55%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (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

Investigations

electrocardiogram abnormal

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

mycobacterium tuberculosis complex test positive

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

1 / 368 (0.27%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

weight increased

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

alcohol poisoning

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

1 / 155 (0.65%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cervical vertebral fracture

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (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 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

exposure via father

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

facial bones fracture

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

fall

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

1 / 176 (0.57%)

1 / 187 (0.53%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

1 / 368 (0.27%)

0 / 26 (0.00%)

3 / 979 (0.31%)

3 / 1002 (0.30%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

femur fracture

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

fibula fracture

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

1 / 176 (0.57%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

hand fracture

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

1 / 155 (0.65%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

head injury

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

1 / 155 (0.65%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

2 / 979 (0.20%)

2 / 1002 (0.20%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

joint dislocation

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

1 / 187 (0.53%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (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

joint injury

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

1 / 187 (0.53%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ligament rupture

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

2 / 979 (0.20%)

2 / 1002 (0.20%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

maternal exposure during pregnancy

alternative dictionary used: MedDRA 22.0

subjects affected / exposed ^[9]

0 / 48 (0.00%)

0 / 122 (0.00%)

0 / 103 (0.00%)

0 / 129 (0.00%)

0 / 66 (0.00%)

0 / 56 (0.00%)

0 / 61 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 74 (0.00%)

0 / 22 (0.00%)

0 / 19 (0.00%)

0 / 129 (0.00%)

0 / 12 (0.00%)

1 / 313 (0.32%)

1 / 324 (0.31%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 78 (0.00%)

0 / 203 (0.00%)

0 / 10 (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 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

multiple fractures

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

1 / 656 (0.15%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

post procedural haemorrhage

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

postoperative wound complication

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (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 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

road traffic accident

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

1 / 155 (0.65%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

2 / 979 (0.20%)

2 / 1002 (0.20%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

skin laceration

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

1 / 368 (0.27%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (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

sternal fracture

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

tendon rupture

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

1 / 187 (0.53%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

thoracic vertebral fracture

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

1 / 347 (0.29%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (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

tibia fracture

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Congenital, familial and genetic disorders

frenulum breve

alternative dictionary used: MedDRA 22.0

subjects affected / exposed ^[10]

0 / 119 (0.00%)

0 / 235 (0.00%)

0 / 244 (0.00%)

0 / 221 (0.00%)

0 / 110 (0.00%)

0 / 131 (0.00%)

0 / 120 (0.00%)

0 / 1 (0.00%)

0 / 112 (0.00%)

0 / 89 (0.00%)

0 / 126 (0.00%)

0 / 53 (0.00%)

0 / 30 (0.00%)

0 / 239 (0.00%)

0 / 14 (0.00%)

1 / 666 (0.15%)

1 / 678 (0.15%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 170 (0.00%)

0 / 453 (0.00%)

0 / 14 (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 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

3 / 979 (0.31%)

3 / 1002 (0.30%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

angina unstable

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

1 / 155 (0.65%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

1 / 656 (0.15%)

0 / 24 (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

aortic valve disease

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

atrial fibrillation

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

1 / 347 (0.29%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cardiac arrest

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (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

coronary artery disease

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

1 / 181 (0.55%)

0 / 3 (0.00%)

1 / 155 (0.65%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

2 / 979 (0.20%)

2 / 1002 (0.20%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

coronary artery stenosis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (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 22.0

subjects affected / exposed

0 / 167 (0.00%)

1 / 357 (0.28%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

1 / 155 (0.65%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

3 / 979 (0.31%)

3 / 1002 (0.30%)

1 / 16 (6.25%)

0 / 6 (0.00%)

1 / 248 (0.40%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

0 / 3

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

myocardial ischaemia

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pericardial effusion

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

1 / 181 (0.55%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

1 / 368 (0.27%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

right ventricular failure

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

sinus node dysfunction

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

1 / 200 (0.50%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

carpal tunnel syndrome

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

3 / 979 (0.31%)

3 / 1002 (0.30%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 4

0 / 0

deaths causally related to treatment / all

0 / 0

cerebrovascular accident

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cognitive disorder

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

generalised tonic-clonic seizure

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

1 / 75 (1.33%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

headache

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

1 / 26 (3.85%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ischaemic stroke

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

1 / 176 (0.57%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

loss of consciousness

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

1 / 357 (0.28%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

multiple sclerosis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

myelopathy

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

sciatica

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

2 / 979 (0.20%)

2 / 1002 (0.20%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

syncope

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

1 / 187 (0.53%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (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

transient ischaemic attack

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

1 / 347 (0.29%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (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

anaemia

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

1 / 167 (0.60%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ear and labyrinth disorders

vertigo

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Eye disorders

optic ischaemic neuropathy

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

1 / 200 (0.50%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

photophobia

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

1 / 26 (3.85%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

abdominal discomfort

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

1 / 368 (0.27%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

abdominal pain

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

1 / 155 (0.65%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

2 / 979 (0.20%)

2 / 1002 (0.20%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

abdominal pain upper

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

1 / 155 (0.65%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

anal fissure

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

1 / 187 (0.53%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

anal fistula

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

1 / 187 (0.53%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

colitis ulcerative

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

1 / 181 (0.55%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

crohn's disease

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

1 / 176 (0.57%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

1 / 656 (0.15%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

diarrhoea

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

diverticular perforation

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

duodenitis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

1 / 350 (0.29%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

gastric perforation

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

gastritis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

1 / 350 (0.29%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

hypertrophic anal papilla

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (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 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

1 / 347 (0.29%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

1 / 181 (0.55%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

lumbar hernia

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

noninfective sialoadenitis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

1 / 75 (1.33%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

oesophageal achalasia

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

2 / 979 (0.20%)

2 / 1002 (0.20%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

oesophagitis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

1 / 350 (0.29%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

small intestinal obstruction

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

bile duct obstruction

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

1 / 187 (0.53%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

bile duct stone

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

1 / 155 (0.65%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

2 / 979 (0.20%)

2 / 1002 (0.20%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 4

0 / 0

deaths causally related to treatment / all

0 / 0

biliary colic

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

2 / 979 (0.20%)

2 / 1002 (0.20%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

cholangitis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

1 / 187 (0.53%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

1 / 368 (0.27%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (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

cholecystitis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

1 / 132 (0.76%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cholestasis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

1 / 181 (0.55%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

hepatic mass

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

1 / 176 (0.57%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Skin and subcutaneous tissue disorders

angioedema

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

1 / 347 (0.29%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

dermatitis allergic

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

erythrodermic psoriasis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

1 / 167 (0.60%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

psoriasis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

3 / 656 (0.46%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

2 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

pustular psoriasis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

1 / 181 (0.55%)

0 / 3 (0.00%)

1 / 155 (0.65%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (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

rash

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (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 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

1 / 200 (0.50%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

acute kidney injury

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

1 / 357 (0.28%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (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 22.0

subjects affected / exposed

0 / 167 (0.00%)

1 / 357 (0.28%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

1 / 49 (2.04%)

1 / 368 (0.27%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

stress urinary incontinence

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

arthralgia

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

1 / 176 (0.57%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

1 / 155 (0.65%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

arthritis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

bursitis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

1 / 187 (0.53%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

intervertebral disc disorder

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

1 / 187 (0.53%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

intervertebral disc protrusion

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

1 / 181 (0.55%)

0 / 3 (0.00%)

1 / 155 (0.65%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (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

musculoskeletal chest pain

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

osteoarthritis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

1 / 357 (0.28%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

1 / 187 (0.53%)

1 / 181 (0.55%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

1 / 200 (0.50%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

4 / 979 (0.41%)

4 / 1002 (0.40%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 1

0 / 0

0 / 1

0 / 0

0 / 5

0 / 0

deaths causally related to treatment / all

0 / 0

psoriatic arthropathy

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

1 / 75 (1.33%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

spinal pain

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

1 / 368 (0.27%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

synovial cyst

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

1 / 368 (0.27%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

synovitis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

abscess intestinal

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

1 / 357 (0.28%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

abscess limb

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

1 / 176 (0.57%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

1 / 368 (0.27%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

abscess oral

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

1 / 350 (0.29%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

appendicitis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

bartholin's abscess

alternative dictionary used: MedDRA 22.0

subjects affected / exposed ^[11]

0 / 48 (0.00%)

0 / 122 (0.00%)

0 / 103 (0.00%)

0 / 129 (0.00%)

0 / 66 (0.00%)

0 / 56 (0.00%)

0 / 61 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 74 (0.00%)

0 / 22 (0.00%)

0 / 19 (0.00%)

1 / 129 (0.78%)

0 / 12 (0.00%)

0 / 313 (0.00%)

0 / 324 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 78 (0.00%)

0 / 203 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

biliary sepsis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

bursitis infective

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cellulitis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

1 / 357 (0.28%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

1 / 187 (0.53%)

0 / 181 (0.00%)

0 / 3 (0.00%)

1 / 155 (0.65%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

1 / 368 (0.27%)

0 / 26 (0.00%)

6 / 979 (0.61%)

6 / 1002 (0.60%)

0 / 16 (0.00%)

0 / 6 (0.00%)

1 / 248 (0.40%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

6 / 8

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cellulitis staphylococcal

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

1 / 132 (0.76%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cholecystitis infective

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

1 / 187 (0.53%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 6

0 / 0

deaths causally related to treatment / all

0 / 0

clostridium difficile infection

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

1 / 176 (0.57%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

diverticulitis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ear infection

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

1 / 200 (0.50%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

eczema infected

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

encephalitis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

erysipelas

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

1 / 347 (0.29%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

3 / 979 (0.31%)

3 / 1002 (0.30%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

2 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

gastroenteritis viral

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

groin abscess

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

haematoma infection

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

infectious mononucleosis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

1 / 181 (0.55%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

necrotising fasciitis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

oesophageal candidiasis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

3 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

otitis media chronic

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

peritonsillar abscess

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

1 / 49 (2.04%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pilonidal cyst

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

1 / 187 (0.53%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (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

pneumonia

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

1 / 200 (0.50%)

1 / 75 (1.33%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

5 / 979 (0.51%)

5 / 1002 (0.50%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

1 / 656 (0.15%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

2 / 2

0 / 0

4 / 5

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pneumonia pseudomonal

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

1 / 181 (0.55%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

postoperative wound infection

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

2 / 979 (0.20%)

2 / 1002 (0.20%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

renal abscess

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

rhinitis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

1 / 656 (0.15%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

sepsis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

1 / 187 (0.53%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

tonsillitis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

2 / 979 (0.20%)

2 / 1002 (0.20%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

tubo-ovarian abscess

alternative dictionary used: MedDRA 22.0

subjects affected / exposed ^[12]

0 / 48 (0.00%)

0 / 122 (0.00%)

0 / 103 (0.00%)

0 / 129 (0.00%)

0 / 66 (0.00%)

0 / 56 (0.00%)

0 / 61 (0.00%)

0 / 2 (0.00%)

0 / 43 (0.00%)

0 / 74 (0.00%)

0 / 22 (0.00%)

0 / 19 (0.00%)

0 / 129 (0.00%)

0 / 12 (0.00%)

1 / 313 (0.32%)

1 / 324 (0.31%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 78 (0.00%)

0 / 203 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

urinary tract infection

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

1 / 347 (0.29%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

wound infection

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (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

diabetes mellitus

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

1 / 350 (0.29%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

1 / 200 (0.50%)

0 / 75 (0.00%)

0 / 49 (0.00%)

1 / 368 (0.27%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (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

hyponatraemia

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

obesity

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

0 / 347 (0.00%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

1 / 200 (0.50%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

1 / 979 (0.10%)

1 / 1002 (0.10%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (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

type 2 diabetes mellitus

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 167 (0.00%)

0 / 357 (0.00%)

1 / 347 (0.29%)

0 / 350 (0.00%)

0 / 176 (0.00%)

0 / 187 (0.00%)

0 / 181 (0.00%)

0 / 3 (0.00%)

0 / 155 (0.00%)

0 / 132 (0.00%)

0 / 200 (0.00%)

0 / 75 (0.00%)

0 / 49 (0.00%)

0 / 368 (0.00%)

0 / 26 (0.00%)

0 / 979 (0.00%)

0 / 1002 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 248 (0.00%)

0 / 656 (0.00%)

0 / 24 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male and 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 and 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 and 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 and female subjects. The number of subjects exposed has been adjusted accordingly.
[5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male and 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 to this adverse event. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male and female subjects. The number of subjects exposed has been adjusted accordingly.
[7] - 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 and female subjects. The number of subjects exposed has been adjusted accordingly.
[8] - 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 and female subjects. The number of subjects exposed has been adjusted accordingly.
[9] - 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 and female subjects. The number of subjects exposed has been adjusted accordingly.
[10] - 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 and female subjects. The number of subjects exposed has been adjusted accordingly.
[11] - 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 and female subjects. The number of subjects exposed has been adjusted accordingly.
[12] - 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 and female subjects. The number of subjects exposed has been adjusted accordingly.

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

Non-serious adverse events	Placebo - Induction period	50 mg ETN - Induction Period	Ixe Q4W - Induction period	Ixe Q2W - Induction period	Ixe/Placebo - Maintenance Period Primary Population	Ixe/Ixe Q4W - Maintenance Period Primary Population	Ixe/Ixe Q12W - Maintenance Period Primary Population	Placebo Resp/Placebo - Maintenance Period Secondary Population	Placebo NonResp/Ixe Q4W - Maintenance Period Secondary Pop	ETNResp/Placebo - Maintenance Period Secondary Population	ETN NonResp/Ixe Q4W - Maintenance Period Secondary Population	Ixe Q4W NonResp/Ixe Q4W - Maintenance Period Secondary Pop	Ixe Q2W NonResp/Ixe Q4W - Maintenance Period Secondary Pop	Ixe Q4W - Maintenance Relapse Population	Placebo Long-Term Extension Period	Ixe Long-Term Extension Period	Total Ixe Long-Term Extension Period	Placebo Post-Treatment Follow-Up	ETN Post-Treatment Follow-Up	Ixe Q12W Post-Treatment Follow-Up	Ixe Q4W Post-Treatment Follow-Up	Ixe Q12W Post-Treatment Follow-Up
Total subjects affected by non serious adverse events
subjects affected / exposed	48 / 167 (28.74%)	141 / 357 (39.50%)	116 / 347 (33.43%)	140 / 350 (40.00%)	56 / 176 (31.82%)	100 / 187 (53.48%)	87 / 181 (48.07%)	2 / 3 (66.67%)	77 / 155 (49.68%)	42 / 132 (31.82%)	106 / 200 (53.00%)	27 / 75 (36.00%)	26 / 49 (53.06%)	136 / 368 (36.96%)	7 / 26 (26.92%)	345 / 979 (35.24%)	345 / 1002 (34.43%)	2 / 16 (12.50%)	3 / 6 (50.00%)	21 / 248 (8.47%)	34 / 656 (5.18%)	0 / 24 (0.00%)
Investigations
mycobacterium tuberculosis complex test positive
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 167 (0.00%)	0 / 357 (0.00%)	0 / 347 (0.00%)	0 / 350 (0.00%)	0 / 176 (0.00%)	3 / 187 (1.60%)	2 / 181 (1.10%)	1 / 3 (33.33%)	1 / 155 (0.65%)	0 / 132 (0.00%)	1 / 200 (0.50%)	0 / 75 (0.00%)	0 / 49 (0.00%)	2 / 368 (0.54%)	0 / 26 (0.00%)	5 / 979 (0.51%)	5 / 1002 (0.50%)	0 / 16 (0.00%)	0 / 6 (0.00%)	0 / 248 (0.00%)	2 / 656 (0.30%)	0 / 24 (0.00%)
occurrences all number	0	0	0	0	0	3	2	1	1	0	1	0	0	2	0	5	5	0	0	0	2	0
Injury, poisoning and procedural complications
muscle strain
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 167 (0.60%)	0 / 357 (0.00%)	2 / 347 (0.58%)	3 / 350 (0.86%)	1 / 176 (0.57%)	2 / 187 (1.07%)	1 / 181 (0.55%)	0 / 3 (0.00%)	0 / 155 (0.00%)	1 / 132 (0.76%)	1 / 200 (0.50%)	2 / 75 (2.67%)	0 / 49 (0.00%)	1 / 368 (0.27%)	2 / 26 (7.69%)	16 / 979 (1.63%)	16 / 1002 (1.60%)	0 / 16 (0.00%)	0 / 6 (0.00%)	1 / 248 (0.40%)	0 / 656 (0.00%)	0 / 24 (0.00%)
occurrences all number	1	0	2	3	1	2	1	0	0	1	1	2	0	1	2	17	17	0	0	1	0	0
Nervous system disorders
headache
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	2 / 167 (1.20%)	21 / 357 (5.88%)	17 / 347 (4.90%)	17 / 350 (4.86%)	7 / 176 (3.98%)	12 / 187 (6.42%)	8 / 181 (4.42%)	0 / 3 (0.00%)	8 / 155 (5.16%)	5 / 132 (3.79%)	4 / 200 (2.00%)	4 / 75 (5.33%)	4 / 49 (8.16%)	12 / 368 (3.26%)	0 / 26 (0.00%)	30 / 979 (3.06%)	30 / 1002 (2.99%)	0 / 16 (0.00%)	1 / 6 (16.67%)	1 / 248 (0.40%)	1 / 656 (0.15%)	0 / 24 (0.00%)
occurrences all number	3	22	21	23	9	14	10	0	14	6	17	4	7	19	0	46	46	0	1	2	1	0
vocal cord paresis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 167 (0.00%)	0 / 357 (0.00%)	0 / 347 (0.00%)	0 / 350 (0.00%)	0 / 176 (0.00%)	0 / 187 (0.00%)	0 / 181 (0.00%)	0 / 3 (0.00%)	0 / 155 (0.00%)	0 / 132 (0.00%)	0 / 200 (0.00%)	0 / 75 (0.00%)	0 / 49 (0.00%)	0 / 368 (0.00%)	0 / 26 (0.00%)	0 / 979 (0.00%)	0 / 1002 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)	0 / 248 (0.00%)	0 / 656 (0.00%)	0 / 24 (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
General disorders and administration site conditions
asthenia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 167 (0.00%)	2 / 357 (0.56%)	3 / 347 (0.86%)	0 / 350 (0.00%)	0 / 176 (0.00%)	1 / 187 (0.53%)	2 / 181 (1.10%)	0 / 3 (0.00%)	1 / 155 (0.65%)	1 / 132 (0.76%)	0 / 200 (0.00%)	0 / 75 (0.00%)	0 / 49 (0.00%)	0 / 368 (0.00%)	0 / 26 (0.00%)	3 / 979 (0.31%)	3 / 1002 (0.30%)	0 / 16 (0.00%)	1 / 6 (16.67%)	0 / 248 (0.00%)	0 / 656 (0.00%)	0 / 24 (0.00%)
occurrences all number	0	2	3	0	0	1	3	0	1	1	0	0	0	0	0	3	3	0	1	0	0	0
injection site erythema
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	2 / 167 (1.20%)	18 / 357 (5.04%)	9 / 347 (2.59%)	12 / 350 (3.43%)	2 / 176 (1.14%)	3 / 187 (1.60%)	4 / 181 (2.21%)	0 / 3 (0.00%)	5 / 155 (3.23%)	1 / 132 (0.76%)	0 / 200 (0.00%)	0 / 75 (0.00%)	0 / 49 (0.00%)	5 / 368 (1.36%)	0 / 26 (0.00%)	5 / 979 (0.51%)	5 / 1002 (0.50%)	0 / 16 (0.00%)	0 / 6 (0.00%)	0 / 248 (0.00%)	0 / 656 (0.00%)	0 / 24 (0.00%)
occurrences all number	2	64	10	20	3	6	4	0	14	3	0	0	0	6	0	19	19	0	0	0	0	0
injection site pain
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	2 / 167 (1.20%)	4 / 357 (1.12%)	5 / 347 (1.44%)	13 / 350 (3.71%)	4 / 176 (2.27%)	1 / 187 (0.53%)	1 / 181 (0.55%)	0 / 3 (0.00%)	1 / 155 (0.65%)	1 / 132 (0.76%)	2 / 200 (1.00%)	0 / 75 (0.00%)	1 / 49 (2.04%)	1 / 368 (0.27%)	1 / 26 (3.85%)	1 / 979 (0.10%)	1 / 1002 (0.10%)	0 / 16 (0.00%)	1 / 6 (16.67%)	0 / 248 (0.00%)	0 / 656 (0.00%)	0 / 24 (0.00%)
occurrences all number	33	5	33	79	22	3	13	0	5	1	4	0	2	1	18	21	21	0	1	0	0	0
injection site reaction
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 167 (0.60%)	38 / 357 (10.64%)	19 / 347 (5.48%)	40 / 350 (11.43%)	0 / 176 (0.00%)	15 / 187 (8.02%)	4 / 181 (2.21%)	0 / 3 (0.00%)	10 / 155 (6.45%)	1 / 132 (0.76%)	20 / 200 (10.00%)	3 / 75 (4.00%)	2 / 49 (4.08%)	19 / 368 (5.16%)	0 / 26 (0.00%)	21 / 979 (2.15%)	21 / 1002 (2.10%)	0 / 16 (0.00%)	0 / 6 (0.00%)	0 / 248 (0.00%)	0 / 656 (0.00%)	0 / 24 (0.00%)
occurrences all number	1	192	30	76	0	69	8	0	42	3	80	21	2	62	0	404	404	0	0	0	0	0
Reproductive system and breast disorders
amenorrhoea
alternative dictionary used: MedDRA 22.0
subjects affected / exposed ^[13]	0 / 48 (0.00%)	0 / 122 (0.00%)	0 / 103 (0.00%)	0 / 129 (0.00%)	0 / 66 (0.00%)	1 / 56 (1.79%)	0 / 61 (0.00%)	0 / 2 (0.00%)	0 / 43 (0.00%)	0 / 43 (0.00%)	0 / 74 (0.00%)	0 / 22 (0.00%)	0 / 19 (0.00%)	0 / 129 (0.00%)	1 / 12 (8.33%)	2 / 313 (0.64%)	2 / 324 (0.62%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 78 (0.00%)	0 / 203 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1	2	2	0	0	0	0	0
Gastrointestinal disorders
diarrhoea
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 167 (0.60%)	2 / 357 (0.56%)	4 / 347 (1.15%)	6 / 350 (1.71%)	4 / 176 (2.27%)	4 / 187 (2.14%)	6 / 181 (3.31%)	0 / 3 (0.00%)	6 / 155 (3.87%)	1 / 132 (0.76%)	5 / 200 (2.50%)	1 / 75 (1.33%)	3 / 49 (6.12%)	5 / 368 (1.36%)	1 / 26 (3.85%)	20 / 979 (2.04%)	20 / 1002 (2.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)	1 / 248 (0.40%)	0 / 656 (0.00%)	0 / 24 (0.00%)
occurrences all number	1	2	4	7	5	4	8	0	6	1	5	1	4	5	1	21	21	0	0	1	0	0
nausea
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	3 / 167 (1.80%)	1 / 357 (0.28%)	5 / 347 (1.44%)	7 / 350 (2.00%)	2 / 176 (1.14%)	2 / 187 (1.07%)	4 / 181 (2.21%)	0 / 3 (0.00%)	6 / 155 (3.87%)	2 / 132 (1.52%)	4 / 200 (2.00%)	1 / 75 (1.33%)	2 / 49 (4.08%)	4 / 368 (1.09%)	0 / 26 (0.00%)	11 / 979 (1.12%)	11 / 1002 (1.10%)	0 / 16 (0.00%)	1 / 6 (16.67%)	1 / 248 (0.40%)	2 / 656 (0.30%)	0 / 24 (0.00%)
occurrences all number	6	2	6	7	3	2	4	0	7	2	6	1	2	4	0	11	11	0	1	1	2	0
Respiratory, thoracic and mediastinal disorders
oropharyngeal pain
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 167 (0.00%)	5 / 357 (1.40%)	5 / 347 (1.44%)	5 / 350 (1.43%)	1 / 176 (0.57%)	3 / 187 (1.60%)	5 / 181 (2.76%)	0 / 3 (0.00%)	2 / 155 (1.29%)	1 / 132 (0.76%)	4 / 200 (2.00%)	1 / 75 (1.33%)	3 / 49 (6.12%)	7 / 368 (1.90%)	0 / 26 (0.00%)	12 / 979 (1.23%)	12 / 1002 (1.20%)	0 / 16 (0.00%)	0 / 6 (0.00%)	0 / 248 (0.00%)	1 / 656 (0.15%)	0 / 24 (0.00%)
occurrences all number	0	7	5	5	2	3	5	0	2	1	4	1	4	7	0	15	15	0	0	0	1	0
Skin and subcutaneous tissue disorders
psoriasis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	5 / 167 (2.99%)	7 / 357 (1.96%)	6 / 347 (1.73%)	5 / 350 (1.43%)	4 / 176 (2.27%)	3 / 187 (1.60%)	5 / 181 (2.76%)	0 / 3 (0.00%)	6 / 155 (3.87%)	2 / 132 (1.52%)	8 / 200 (4.00%)	3 / 75 (4.00%)	3 / 49 (6.12%)	12 / 368 (3.26%)	1 / 26 (3.85%)	28 / 979 (2.86%)	28 / 1002 (2.79%)	0 / 16 (0.00%)	0 / 6 (0.00%)	3 / 248 (1.21%)	6 / 656 (0.91%)	0 / 24 (0.00%)
occurrences all number	5	7	6	5	4	4	6	0	8	3	10	5	3	18	1	31	31	0	0	3	6	0
Musculoskeletal and connective tissue disorders
arthralgia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	5 / 167 (2.99%)	9 / 357 (2.52%)	8 / 347 (2.31%)	6 / 350 (1.71%)	5 / 176 (2.84%)	8 / 187 (4.28%)	10 / 181 (5.52%)	0 / 3 (0.00%)	6 / 155 (3.87%)	8 / 132 (6.06%)	10 / 200 (5.00%)	1 / 75 (1.33%)	1 / 49 (2.04%)	13 / 368 (3.53%)	0 / 26 (0.00%)	48 / 979 (4.90%)	48 / 1002 (4.79%)	0 / 16 (0.00%)	0 / 6 (0.00%)	3 / 248 (1.21%)	5 / 656 (0.76%)	0 / 24 (0.00%)
occurrences all number	6	10	10	6	6	10	11	0	7	10	11	1	1	14	0	60	60	0	0	3	5	0
arthritis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 167 (0.00%)	0 / 357 (0.00%)	0 / 347 (0.00%)	0 / 350 (0.00%)	0 / 176 (0.00%)	0 / 187 (0.00%)	0 / 181 (0.00%)	0 / 3 (0.00%)	0 / 155 (0.00%)	1 / 132 (0.76%)	2 / 200 (1.00%)	0 / 75 (0.00%)	0 / 49 (0.00%)	1 / 368 (0.27%)	0 / 26 (0.00%)	4 / 979 (0.41%)	4 / 1002 (0.40%)	0 / 16 (0.00%)	1 / 6 (16.67%)	1 / 248 (0.40%)	0 / 656 (0.00%)	0 / 24 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	2	0	0	1	0	4	4	0	1	1	0	0
back pain
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	3 / 167 (1.80%)	5 / 357 (1.40%)	2 / 347 (0.58%)	4 / 350 (1.14%)	1 / 176 (0.57%)	9 / 187 (4.81%)	6 / 181 (3.31%)	0 / 3 (0.00%)	9 / 155 (5.81%)	2 / 132 (1.52%)	6 / 200 (3.00%)	3 / 75 (4.00%)	3 / 49 (6.12%)	12 / 368 (3.26%)	1 / 26 (3.85%)	40 / 979 (4.09%)	40 / 1002 (3.99%)	0 / 16 (0.00%)	0 / 6 (0.00%)	1 / 248 (0.40%)	0 / 656 (0.00%)	0 / 24 (0.00%)
occurrences all number	3	7	2	4	2	10	8	0	9	7	6	3	3	15	1	50	50	0	0	1	0	0
musculoskeletal chest pain
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 167 (0.00%)	1 / 357 (0.28%)	0 / 347 (0.00%)	2 / 350 (0.57%)	1 / 176 (0.57%)	0 / 187 (0.00%)	0 / 181 (0.00%)	1 / 3 (33.33%)	0 / 155 (0.00%)	0 / 132 (0.00%)	2 / 200 (1.00%)	0 / 75 (0.00%)	1 / 49 (2.04%)	0 / 368 (0.00%)	0 / 26 (0.00%)	3 / 979 (0.31%)	3 / 1002 (0.30%)	0 / 16 (0.00%)	0 / 6 (0.00%)	0 / 248 (0.00%)	0 / 656 (0.00%)	0 / 24 (0.00%)
occurrences all number	0	1	0	2	1	0	0	1	0	0	2	0	1	0	0	3	3	0	0	0	0	0
psoriatic arthropathy
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	2 / 167 (1.20%)	1 / 357 (0.28%)	2 / 347 (0.58%)	0 / 350 (0.00%)	1 / 176 (0.57%)	1 / 187 (0.53%)	0 / 181 (0.00%)	0 / 3 (0.00%)	1 / 155 (0.65%)	3 / 132 (2.27%)	1 / 200 (0.50%)	1 / 75 (1.33%)	3 / 49 (6.12%)	0 / 368 (0.00%)	0 / 26 (0.00%)	5 / 979 (0.51%)	5 / 1002 (0.50%)	0 / 16 (0.00%)	0 / 6 (0.00%)	0 / 248 (0.00%)	4 / 656 (0.61%)	0 / 24 (0.00%)
occurrences all number	2	1	2	0	1	1	0	0	1	4	1	1	4	0	0	6	6	0	0	0	4	0
Infections and infestations
bronchitis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	3 / 167 (1.80%)	5 / 357 (1.40%)	4 / 347 (1.15%)	5 / 350 (1.43%)	3 / 176 (1.70%)	7 / 187 (3.74%)	10 / 181 (5.52%)	0 / 3 (0.00%)	2 / 155 (1.29%)	0 / 132 (0.00%)	10 / 200 (5.00%)	1 / 75 (1.33%)	2 / 49 (4.08%)	11 / 368 (2.99%)	1 / 26 (3.85%)	38 / 979 (3.88%)	38 / 1002 (3.79%)	0 / 16 (0.00%)	0 / 6 (0.00%)	3 / 248 (1.21%)	3 / 656 (0.46%)	0 / 24 (0.00%)
occurrences all number	3	5	4	5	3	8	12	0	2	0	11	1	3	11	1	52	52	0	0	3	3	0
ear infection
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 167 (0.60%)	0 / 357 (0.00%)	2 / 347 (0.58%)	3 / 350 (0.86%)	0 / 176 (0.00%)	2 / 187 (1.07%)	1 / 181 (0.55%)	0 / 3 (0.00%)	1 / 155 (0.65%)	1 / 132 (0.76%)	3 / 200 (1.50%)	1 / 75 (1.33%)	1 / 49 (2.04%)	1 / 368 (0.27%)	0 / 26 (0.00%)	12 / 979 (1.23%)	12 / 1002 (1.20%)	1 / 16 (6.25%)	0 / 6 (0.00%)	0 / 248 (0.00%)	1 / 656 (0.15%)	0 / 24 (0.00%)
occurrences all number	1	0	2	3	0	3	1	0	1	1	3	1	1	1	0	15	15	1	0	0	1	0
nasopharyngitis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	17 / 167 (10.18%)	37 / 357 (10.36%)	28 / 347 (8.07%)	34 / 350 (9.71%)	19 / 176 (10.80%)	32 / 187 (17.11%)	24 / 181 (13.26%)	0 / 3 (0.00%)	29 / 155 (18.71%)	19 / 132 (14.39%)	35 / 200 (17.50%)	12 / 75 (16.00%)	8 / 49 (16.33%)	41 / 368 (11.14%)	0 / 26 (0.00%)	125 / 979 (12.77%)	125 / 1002 (12.48%)	0 / 16 (0.00%)	1 / 6 (16.67%)	3 / 248 (1.21%)	4 / 656 (0.61%)	0 / 24 (0.00%)
occurrences all number	21	41	40	34	22	42	31	0	42	24	47	13	11	61	0	195	195	0	1	3	4	0
pharyngitis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 167 (0.00%)	5 / 357 (1.40%)	5 / 347 (1.44%)	4 / 350 (1.14%)	1 / 176 (0.57%)	11 / 187 (5.88%)	3 / 181 (1.66%)	0 / 3 (0.00%)	3 / 155 (1.94%)	1 / 132 (0.76%)	7 / 200 (3.50%)	2 / 75 (2.67%)	4 / 49 (8.16%)	11 / 368 (2.99%)	0 / 26 (0.00%)	19 / 979 (1.94%)	19 / 1002 (1.90%)	0 / 16 (0.00%)	0 / 6 (0.00%)	3 / 248 (1.21%)	2 / 656 (0.30%)	0 / 24 (0.00%)
occurrences all number	0	5	5	4	1	12	3	0	7	1	7	2	5	13	0	26	26	0	0	4	2	0
sinusitis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 167 (0.00%)	4 / 357 (1.12%)	6 / 347 (1.73%)	2 / 350 (0.57%)	3 / 176 (1.70%)	10 / 187 (5.35%)	6 / 181 (3.31%)	0 / 3 (0.00%)	7 / 155 (4.52%)	1 / 132 (0.76%)	7 / 200 (3.50%)	1 / 75 (1.33%)	0 / 49 (0.00%)	12 / 368 (3.26%)	0 / 26 (0.00%)	38 / 979 (3.88%)	38 / 1002 (3.79%)	0 / 16 (0.00%)	0 / 6 (0.00%)	1 / 248 (0.40%)	3 / 656 (0.46%)	0 / 24 (0.00%)
occurrences all number	0	4	6	2	3	10	6	0	7	1	7	1	0	12	0	56	56	0	0	1	3	0
upper respiratory tract infection
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	7 / 167 (4.19%)	27 / 357 (7.56%)	16 / 347 (4.61%)	20 / 350 (5.71%)	14 / 176 (7.95%)	25 / 187 (13.37%)	21 / 181 (11.60%)	0 / 3 (0.00%)	20 / 155 (12.90%)	8 / 132 (6.06%)	21 / 200 (10.50%)	7 / 75 (9.33%)	7 / 49 (14.29%)	21 / 368 (5.71%)	2 / 26 (7.69%)	108 / 979 (11.03%)	108 / 1002 (10.78%)	0 / 16 (0.00%)	0 / 6 (0.00%)	2 / 248 (0.81%)	4 / 656 (0.61%)	0 / 24 (0.00%)
occurrences all number	8	27	19	21	19	30	23	0	23	9	28	10	9	32	4	166	166	0	0	2	4	0
urinary tract infection
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	2 / 167 (1.20%)	2 / 357 (0.56%)	7 / 347 (2.02%)	5 / 350 (1.43%)	3 / 176 (1.70%)	5 / 187 (2.67%)	7 / 181 (3.87%)	1 / 3 (33.33%)	8 / 155 (5.16%)	0 / 132 (0.00%)	8 / 200 (4.00%)	1 / 75 (1.33%)	3 / 49 (6.12%)	4 / 368 (1.09%)	1 / 26 (3.85%)	27 / 979 (2.76%)	27 / 1002 (2.69%)	0 / 16 (0.00%)	0 / 6 (0.00%)	0 / 248 (0.00%)	1 / 656 (0.15%)	0 / 24 (0.00%)
occurrences all number	2	2	7	5	3	9	9	1	8	0	14	1	3	5	1	30	30	0	0	0	1	0
vulvovaginal candidiasis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed ^[14]	0 / 48 (0.00%)	1 / 122 (0.82%)	0 / 103 (0.00%)	0 / 129 (0.00%)	1 / 66 (1.52%)	0 / 56 (0.00%)	0 / 61 (0.00%)	0 / 2 (0.00%)	1 / 43 (2.33%)	0 / 43 (0.00%)	2 / 74 (2.70%)	2 / 22 (9.09%)	0 / 19 (0.00%)	1 / 129 (0.78%)	0 / 12 (0.00%)	3 / 313 (0.96%)	3 / 324 (0.93%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 78 (0.00%)	0 / 203 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0	1	0	0	0	1	0	2	2	0	1	0	3	3	0	0	0	0	0

Notes
[13] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male and female subjects. The number of subjects exposed has been adjusted accordingly.
[14] - 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 and female subjects. The number of subjects exposed has been adjusted accordingly.

More information

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Were there any global substantial amendments to the protocol? Yes

15 Mar 2012

Changes to protocol (a) are as follows: o Including monthly urine pregnancy testing for women of childbearing potential o Clarifying under “Treatment Assignment for Non-Responders” that patients who have no response. o Removing evaluation of joint pain as a secondary objective o Added a definition of concomitant topical products o Changing the definition of “rebound” to add an evaluation of PASI so that rebound is now defined o Stratifying randomization by center, changing the primary analyses for categorical efficacy outcomes to a Cochran-Mantel-Haenszel (CMH) test stratified by center, specifying the pooling strategy o Using a MMRM approach for the primary analysis of continuous variables o Revised enrollment criteria to exclude participants who are positive for hepatitis B surface antigent or positive for anti- hepatitis B core antibody o Added new exclusion criterion and discontinuation criteria, revised hepatic safety monitoring rules and lab tests, and a discontinuation rule for participants who develop symptoms of lupus-like syndrome

31 Oct 2012

Changes to protocol (b) are as follows: o Modified exclusion criterion to allow enrollment of patients who have had previous infection with hepatitis B virus (HBV) o Added discontinuation requirement for positive HBV DNA test results o Added section of hepatitis B monitoring o Corrected inclusion criterion to require use of spermicide in conjunction with a diaphragm o Clarified exclusion criterion to define participants with serious cardiac conditions o Clarified descriptions of premedication to indicate that acceptable medications are not restricted to the examples given o Updated the PASI 75 assumption for etanercept at Week 12 to 53%

04 Feb 2015

Changes to protocol (c) are as follows: o Modified treatment administered in the Long-Term Extension Period o Modified existing text regarding the discontinuation of placebo injections after the study is unblinded o Modified the requirements for discontinuation of inadvertently enrolled participants o Modified permitted concomitant medications o Modified concomitant medications o Modified language on permitted concomitant medication and the permitted drug delivery devices

28 Mar 2017

Changes to protocol (d) are as follows: Added IBD adjudication consistent with compound-level decision as IBD, specifically Crohn’s Disease and ulcerative colitis, has been demonstrated to occur more frequently in people with psoriasis. IBD is a reasonably anticipated event  Added clarity on dosing windows for Long-Term Extension Period

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, Randomized, Double-Blind, Placebo-Controlled Study Comparing the Efficacy and Safety of LY2439821 to Etanercept and Placebo in Patients with Moderate-to-Severe Plaque Psoriasis

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Participants with a Static Physician Global Assessment (sPGA) of (0,1) (Efficacy of ixekizumab in participants with moderate to severe chronic plaque psoriasis. Measure: Static Physician Global Assessment [sPGA])

Primary: Percentage of Participants with a Static Physician Global Assessment (sPGA) of (0,1) (Efficacy of ixekizumab in participants with moderate to severe chronic plaque psoriasis. Measure: Static Physician Global Assessment [sPGA])

Primary: Percentage of Participants achieving Psoriasis Area and Severity Index (PASI) ≥75% (PASI75) Improvement (Efficacy of ixekizumab in participants with moderate to severe chronic plaque psoriasis. Measure: Psoriasis Area and Severity Index [PASI])

Primary: Percentage of Participants achieving Psoriasis Area and Severity Index (PASI) ≥75% (PASI75) Improvement (Efficacy of ixekizumab in participants with moderate to severe chronic plaque psoriasis. Measure: Psoriasis Area and Severity Index [PASI])

Secondary: Percentage of Participants Achieving an sPGA (0) (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: [sPGA])

Secondary: Percentage of Participants Achieving an sPGA (0) (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: [sPGA])

Secondary: Percentage of Participants Achieving PASI 90% (PASI90) (Efficacy of ixekizumab in participants with moderate to severe chronic plaque psoriasis. Measure: [PASI])

Secondary: Percentage of Participants Achieving PASI 90% (PASI90) (Efficacy of ixekizumab in participants with moderate to severe chronic plaque psoriasis. Measure: [PASI])

Secondary: Percentage of Participants Achieving PASI 100% (PASI100)

Secondary: Percentage of Participants Achieving PASI 100% (PASI100)

Secondary: Percentage of Participants Maintaining an sPGA (0,1) from Week 12 after Re-randomization at start of Maintenance Dosing Period to Week 60

Secondary: Percentage of Participants Maintaining an sPGA (0,1) from Week 12 after Re-randomization at start of Maintenance Dosing Period to Week 60

Secondary: Percentage of Participants with Itching Severity (Itch Numeric Rating Scale [NRI]) Score ≥4 Point Reduction from Baseline

Secondary: Percentage of Participants with Itching Severity (Itch Numeric Rating Scale [NRI]) Score ≥4 Point Reduction from Baseline

Secondary: Change from baseline in Dermatology-Specific Quality of Life Index (DLQI) Total Score (Quality of Life and Outcome Assessments. Measures: Participant Reported Outcomes [PRO])

Secondary: Change from baseline in Dermatology-Specific Quality of Life Index (DLQI) Total Score (Quality of Life and Outcome Assessments. Measures: Participant Reported Outcomes [PRO])

Secondary: Change from Baseline in Nail Psoriasis Severity Index (NAPSI)

Secondary: Change from Baseline in Nail Psoriasis Severity Index (NAPSI)

Secondary: Change from Baseline Psoriasis Scalp Severity Index (PSSI) Score

Secondary: Change from Baseline Psoriasis Scalp Severity Index (PSSI) Score

Secondary: Change from Baseline in Percent of Body Surface Area (BSA) involvement of psoriasis

Secondary: Change from Baseline in Percent of Body Surface Area (BSA) involvement of psoriasis

Secondary: Change from baseline in Quick Inventory of Depressive Symptomatology-Self Report 16 items (QIDS-SR16) Total Score

Secondary: Change from baseline in Quick Inventory of Depressive Symptomatology-Self Report 16 items (QIDS-SR16) Total Score

Secondary: Change from Baseline in Absenteeism of Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO)

Secondary: Change from Baseline in Absenteeism of Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO)

Secondary: Change From Baseline in Activity Impairment Score of WPAI-PSO

Secondary: Change From Baseline in Activity Impairment Score of WPAI-PSO

Secondary: Change From Baseline in Presenteeism Score of WPAI-PSO

Secondary: Change From Baseline in Presenteeism Score of WPAI-PSO

Secondary: Change From Baseline in Work Productivity Loss Score of WPAI-PSO

Secondary: Change From Baseline in Work Productivity Loss Score of WPAI-PSO

Secondary: Change from baseline in Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) and Physical Component Summary (PCS) and Mental Component Summary (MCS

Secondary: Change from baseline in Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) and Physical Component Summary (PCS) and Mental Component Summary (MCS

Secondary: Change from baseline in Patient's Global Assessment (PatGA) of Disease Severity

Secondary: Change from baseline in Patient's Global Assessment (PatGA) of Disease Severity

Secondary: Percentage of Participants achieving Palmoplantar PASI (PPASI) of of ≥50% (PPASI50), ≥75% (PPASI75) or 100% (PPASI100)

Secondary: Percentage of Participants achieving Palmoplantar PASI (PPASI) of of ≥50% (PPASI50), ≥75% (PPASI75) or 100% (PPASI100)

Secondary: Percentage of participants with Anti-Ixekizumab Antibodies

Secondary: Percentage of participants with Anti-Ixekizumab Antibodies

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Comparing the Efficacy and Safety of LY2439821 to Etanercept and Placebo in Patients with Moderate-to-Severe Plaque Psoriasis