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Clinical Trial Results:
A Multicenter Study with a Randomized, Double-Blind, Placebo-Controlled Induction Dosing Period Followed by a Randomized Maintenance Dosing Period and a Long-Term Extension Period to Evaluate the Efficacy and Safety of LY2439821 in Patients with Moderate-to-Severe Plaque Psoriasis

Summary
EudraCT number	2011-002970-22
Trial protocol	DE GB HU PL IT DK
Global end of trial date	20 Sep 2018

Results information
Results version number	v1(current)
This version publication date	04 Oct 2019
First version publication date	04 Oct 2019
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-RHAZ

ISRCTN number

US NCT number

NCT01474512

WHO universal trial number (UTN)

Other trial identifiers

Trial Number: 12972

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

20 Sep 2018

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

20 Sep 2018

Was the trial ended prematurely?

Main objective of the trial

This study will assess the safety and efficacy of LY2439821 compared to 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

16 Nov 2011

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Canada: 212

Country: Number of subjects enrolled

Romania: 13

Country: Number of subjects enrolled

Hungary: 66

Country: Number of subjects enrolled

United States: 461

Country: Number of subjects enrolled

Japan: 33

Country: Number of subjects enrolled

Denmark: 16

Country: Number of subjects enrolled

Poland: 139

Country: Number of subjects enrolled

Italy: 6

Country: Number of subjects enrolled

United Kingdom: 21

Country: Number of subjects enrolled

Australia: 42

Country: Number of subjects enrolled

Germany: 287

Worldwide total number of subjects

1296

EEA total number of subjects

548

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)

1201

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Induction Period (Week 0 to 12), Maintenance Period (Week 12 to 60); Long term Extension (Week 60 to 264) and Post treatment ( last treatment visit (week 264), or Early Termination Visit (ETV) up to a minimum of 12 weeks following that visit.

Screening details

Participants received Ixekizumab (ixe) as responders (Resp, sPGA 0/1) in Induction (IND) re-randomized to receive ixe Q4W, Q12W or placebo (PBO) in Maintenance (MAIN) [Primary Population (Pop)]. In MAIN, non-responders (Non-Resp, sPGA >1) in IND received ixe Q4W, PBO Resp in IND received PBO (Secondary Pop). Ixe or PBO continued to end of study.

Period 1 title

Induction Period

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

Placebo- Induction Period

Arm description

Placebo was administered as 2 subcutaneous (SC) injections at week 0 then 1 PBO (SC) injection every 2 weeks (Q2W) up to Week 10.

Arm type

Experimental

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 2 subcutaneous (SC) injections at week 0 then 1 PBO (SC) injection every 2 weeks (Q2W) up to Week 10.

Ixe Q4W Induction Period

Arm description

160 milligrams (mg) ixe was administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection every 4 weeks (Q4W). Placebo was administered as 1 SC injection at Weeks 2, 6, and 10.

Arm type

Experimental

Investigational medicinal product name

Ixe Q4W

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

160 milligrams (mg) ixe was administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection every 4 weeks (Q4W). Placebo was administered as 1 SC injection at Weeks 2, 6, and 10.

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.

Arm type

Experimental

Investigational medicinal product name

Ixe Q2W

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.

Number of subjects in period 1	Placebo- Induction Period	Ixe Q4W Induction Period	Ixe Q2W - Induction Period
Started	431	432	433
Received Study Drug	431	432	433
Completed	407	408	415
Not completed	24	24	18
Consent withdrawn by subject	6	6	5
Adverse event, non-fatal	6	10	10
Sponsor Decision	1	1	1
Lost to follow-up	1	-	2
Lack of efficacy	7	1	-
Protocol deviation	3	6	-

Period 2 title

Maintenance Period

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 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 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 at Week 12 followed by 80 mg ixe as 1 SC injection every 12 weeks (Q12W) up to and including Week 56. Pbo injection was given in between doses Q4W to maintain blindness.

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

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

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 Non-Resp/Ixe Q4W - Maintenance Period Secondary Pop

Arm description

Participants who received placebo in Induction Period (Weeks 0 to 10) and classified as non-responders 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

Ixe Q4W Non-Resp/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 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

Ixe Q2W Non-Resp/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 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

Ixe Q4W - Maintenance Period Relapsed Population

Arm description

Participants who relapsed during maintenance period prior to long term received, Ixe 80 mg as 1 SC injection Q4W for the remainder of the study to evaluate whether the response observed earlier could be regained on treatment with a higher dose.

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

Number of subjects in period 2	Ixe/Placebo- Maintenance Period Primary Pop	Ixe/Ixe Q12W - Maintenance Period Primary Pop	Ixe/Ixe Q4W - Maintenance Period Primary Pop	Placebo Resp/Placebo - Maintenance Period Secondary Pop	Placebo Non-Resp/Ixe Q4W - Maintenance Period Secondary Pop	Ixe Q4W Non-Resp/Ixe Q4W- Maintenance Period Secondary Pop	Ixe Q2W Non-Resp/Ixe Q4W - Maintenance Period Secondary Pop	Ixe Q4W - Maintenance Period Relapsed Population
Started	226	227	229	16	391	78	62	348
Received Study Drug	226	227	229	16	391	78	62	348
Relapsed Population Received Drug	0 ^[1]	0 ^[2]	0 ^[3]	0 ^[4]	0 ^[5]	0 ^[6]	0 ^[7]	348
Relapsed Population Completers	0 ^[8]	0 ^[9]	0 ^[10]	0 ^[11]	0 ^[12]	0 ^[13]	0 ^[14]	321
Completed	24	108	177	6	350	62	44	321
Not completed	202	119	52	10	41	16	18	27
Adverse event, serious fatal	-	-	2	-	-	-	-	-
Consent withdrawn by subject	6	2	3	1	6	3	1	4
Physician decision	-	-	1	-	-	-	-	1
Clinical Relapse	1	-	-	-	-	-	-	1
Adverse event, non-fatal	4	2	7	-	19	1	3	8
Investigator Decision	-	-	-	-	2	-	-	-
Treated but Discontinued in Induction	-	1	-	-	-	-	-	-
Lost to follow-up	3	3	-	-	2	1	1	5
Relapsed (sPGA ≥3)	186	111	39	9	-	-	-	-
Lack of efficacy	1	-	-	-	11	11	12	6
Protocol deviation	1	-	-	-	1	-	1	2

Notes
[1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: All participants who received at least one dose of study drug are a subset to those who started the period.
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: All participants who received at least one dose of study drug are a subset to those who started the period.
[3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: All participants who received at least one dose of study drug are a subset to those who started the period.
[4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: All participants who received at least one dose of study drug are a subset to those who started the period.
[5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: All participants who received at least one dose of study drug are a subset to those who started the period.
[6] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: All participants who received at least one dose of study drug are a subset to those who started the period.
[7] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: All participants who received at least one dose of study drug are a subset to those who started the period.
[8] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: All participants who received at least one dose of study drug are a subset to those who started the period.
[9] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: All participants who received at least one dose of study drug are a subset to those who started the period.
[10] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: All participants who received at least one dose of study drug are a subset to those who started the period.
[11] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: All participants who received at least one dose of study drug are a subset to those who started the period.
[12] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: All participants who received at least one dose of study drug are a subset to those who started the period.
[13] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: All participants who received at least one dose of study drug are a subset to those who started the period.
[14] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: All participants who received at least one dose of study drug are a subset to those who started the period.

Period 3 title

Long-Term Extension Period

Is this the baseline period?

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Placebo Long-Term Extension

Arm description

Participants who received placebo at the start of the long-term extension period and remained on placebo. Participants who received placebo at the start of long-term extension (Week 60) then switched to Ixe.

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

PBO participants who switched to IXE or discontinued from the study at Week 60.

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 LTE period.

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.

Number of subjects in period 3	Placebo Long-Term Extension	Ixe Long-Term Extension	Total Ixe Long-Term Extension
Started	26	1054	1075
Completed	0	836	855
Not completed	26	218	220
Adverse event, serious fatal	-	9	9
Parent/Caregiver Decision	-	1	1
Consent withdrawn by subject	3	61	61
Physician decision	-	21	21
Clinical Relapse	-	9	9
Adverse event, non-fatal	1	57	58
Sponsor Decision	-	6	6
Lost to follow-up	-	25	25
Switched From PBO to Ixe	21	-	-
Lack of efficacy	1	24	25
Protocol deviation	-	5	5

Period 4 title

Post-Treatment Follow-Up

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 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 injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants who received PBO 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 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 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 Q4W 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 Q4W 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 Q2W 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 Q2W 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 ^[15]	Placebo Post-Treatment Follow-Up	Ixe Q12W Post-Treatment Follow-Up	Ixe Q4W Post-Treatment Follow-Up	Ixe Q2W Post-Treatment Follow-Up
Started	18	25	700	285
Completed	0	17	544	239
Not completed	18	8	156	46
Parent/Caregiver Decision	1	-	-	1
Adverse event, serious fatal	-	-	1	-
Consent withdrawn by subject	3	2	36	17
Physician decision	-	-	4	5
Clinical Relapse	-	-	6	2
Adverse event, non-fatal	8	2	58	11
Sponsor Decision	1	-	4	-
Lost to follow-up	-	-	12	7
Lack of efficacy	3	2	31	3
Protocol deviation	2	2	4	-

Notes
[15] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: All participants who received at least one dose of study drug are a subset to those who started the period.

Baseline characteristics

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Reporting group title

Placebo- Induction Period

Reporting group description

Placebo was administered as 2 subcutaneous (SC) injections at week 0 then 1 PBO (SC) injection every 2 weeks (Q2W) up to Week 10.

Reporting group title

Ixe Q4W Induction Period

Reporting group description

160 milligrams (mg) ixe was administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection every 4 weeks (Q4W). Placebo was administered as 1 SC injection at Weeks 2, 6, and 10.

Reporting group title

Ixe Q2W - Induction Period

Reporting group 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.

Reporting group values	Placebo- Induction Period	Ixe Q4W Induction Period	Ixe Q2W - Induction Period	Total
Number of subjects	431	432	433	1296
Age categorical
Units: Subjects
In utero				0
Preterm newborn infants (gestational age < 37 wks)				0
Newborns (0-27 days)				0
Infants and toddlers (28 days-23 months)				0
Children (2-11 years)				0
Adolescents (12-17 years)				0
Adults (18-64 years)				0
From 65-84 years				0
85 years and over				0
Age continuous
Units: years
arithmetic mean (standard deviation)	46.4 ( 13.40 )	45.6 ( 12.95 )	45.1 ( 12.40 )	-
Gender categorical
Units: Subjects
Female	128	143	142	413
Male	303	289	291	883
Region of Enrollment
Units: Subjects
Canada	77	69	66	212
Romania	8	3	2	13
Hungary	23	17	26	66
United States	146	156	159	461
Japan	13	12	8	33
Denmark	4	4	8	16
Poland	43	41	55	139
Italy	3	2	1	6
United Kingdom	7	7	7	21
Australia	19	15	8	42
Germany	88	106	93	287

End points

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Reporting group title

Placebo- Induction Period

Reporting group description

Placebo was administered as 2 subcutaneous (SC) injections at week 0 then 1 PBO (SC) injection every 2 weeks (Q2W) up to Week 10.

Reporting group title

Ixe Q4W Induction Period

Reporting group description

160 milligrams (mg) ixe was administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection every 4 weeks (Q4W). Placebo was administered as 1 SC injection at Weeks 2, 6, and 10.

Reporting group title

Ixe Q2W - Induction Period

Reporting group 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.

Reporting group title

Ixe/Placebo- Maintenance Period Primary Pop

Reporting group description

Reporting group title

Ixe/Ixe Q12W - Maintenance Period Primary Pop

Reporting group description

Reporting group title

Ixe/Ixe Q4W - Maintenance Period Primary Pop

Reporting group description

Reporting group title

Placebo Resp/Placebo - Maintenance Period Secondary Pop

Reporting group description

Reporting group title

Placebo Non-Resp/Ixe Q4W - Maintenance Period Secondary Pop

Reporting group description

Reporting group title

Ixe Q4W Non-Resp/Ixe Q4W- Maintenance Period Secondary Pop

Reporting group description

Reporting group title

Ixe Q2W Non-Resp/Ixe Q4W - Maintenance Period Secondary Pop

Reporting group description

Reporting group title

Ixe Q4W - Maintenance Period Relapsed Population

Reporting group description

Reporting group title

Placebo Long-Term Extension

Reporting group description

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 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 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 Q4W 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 Q2W prior to entering the Post-Treatment Follow-Up period (a 12-24 week period after their last scheduled treatment visit).

Subject analysis set title

Ixe/Placebo

Subject analysis set type

Per protocol

Subject analysis set description

Participants who received ixe (Q2W or Q4W) in Induction Period who were re-randomized at Week 12 and administered placebo as 2 SC injections at Week 12 followed by placebo as 1 SC injection Q4W up to and including Week 56 (Maintenance Period).

Subject analysis set title

Ixe/Q12W

Subject analysis set type

Per protocol

Subject analysis set description

Participants who received ixe (Q2W or Q4W) in Induction Period who were re-randomized at Week 12 and were administered 80 mg ixe as 1 SC injection at Week 12 followed by 80 mg ixe as 1 SC injection Q12W up to and including Week 56 (Maintenance Period).

Subject analysis set title

Ixe/Q4W

Subject analysis set type

Per protocol

Subject analysis set description

Participants who received ixe (Q2W or Q4W) in Induction Period who were re-randomized at Week 12 and 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 (Maintenance Period).

Subject analysis set title

Ixe Q4W - Maintenance Period

Subject analysis set type

Per protocol

Subject analysis set description

80 mg ixe administered as 1 SC injection Q4W from Week 12 up to Week 60

Subject analysis set title

Ixe Q12W - Maintenance Period

Subject analysis set type

Per protocol

Subject analysis set description

80 mg ixe administered as 1 SC injection Q12W from Week 12 up to Week 60

Subject analysis set title

Ixe Q2W

Subject analysis set type

Sub-group analysis

Subject analysis set description

All randomized participants with Ctrough ss at specified timepoints.

Subject analysis set title

IxeQ4W

Subject analysis set type

Sub-group analysis

Subject analysis set description

All randomized participants with Ctrough ss at specified timepoints

Primary: Percentage of Participants with static Physician Global Assessment (sPGA) of 0 or 1 (Efficacy of Ixekizumab in participants with moderate to severe plaque Ps Measure: sPGA)

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End point title

Percentage of Participants with static Physician Global Assessment (sPGA) of 0 or 1 (Efficacy of Ixekizumab in participants with moderate to severe plaque Ps 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. Participants Ps were 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.

End point type

Primary

End point timeframe

Week 12

End point values	Placebo- Induction Period	Ixe Q4W Induction Period	Ixe Q2W - Induction Period
Number of subjects analysed	431 ^[1]	432 ^[2]	433 ^[3]
Units: percentage of participants
number (not applicable)	3.2	76.4	81.8

Notes
[1] - All randomized participants or non-responders for Non-Responder Imputation (NRI) analysis.
[2] - All randomized participants or non-responders for Non-Responder Imputation (NRI) analysis.
[3] - All randomized participants or non-responders for Non-Responder Imputation (NRI) analysis.

Percentage of Participants with Static Physician

Comparison groups

Placebo- Induction Period v Ixe Q4W Induction Period

Number of subjects included in analysis

863

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[4]

Method

Regression, Logistic

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[4] - Logistic Regression analysis included treatment, geographic region, previous non-biologic systemic therapy and baseline weight category as factors.

Percentage of Participants with Static Physician

Comparison groups

Placebo- Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

864

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[5]

Method

Regression, Logistic

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[5] - Logistic Regression analysis included treatment, geographic region, previous non-biologic systemic therapy and baseline weight category as factors

Primary: Percentage of Participants achieving ≥75% Improvement in Ps Area and Severity Index (PASI75) (Efficacy of Ixekizumab in participants with moderate to severe plaque psoriasis Measure: PASI)

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End point title

Percentage of Participants achieving ≥75% Improvement in Ps Area and Severity Index (PASI75) (Efficacy of Ixekizumab in participants with moderate to severe 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 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.

End point type

Primary

End point timeframe

Week 12

End point values	Placebo- Induction Period	Ixe Q4W Induction Period	Ixe Q2W - Induction Period
Number of subjects analysed	431 ^[6]	432 ^[7]	433 ^[8]
Units: percentage of participants
number (not applicable)	3.9	82.6	89.1

Notes
[6] - All randomized participants and non-responders for NRI analysis.
[7] - All randomized participants and non-responders for NRI analysis.
[8] - All randomized participants and non-responders for NRI analysis.

Percentage of Participants achieving ≥75% Improve

Comparison groups

Placebo- Induction Period v Ixe Q4W Induction Period

Number of subjects included in analysis

863

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[9]

Method

Regression, Logistic

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[9] - Logistic Regression analysis included treatment, geographic region, previous non-biologic systemic therapy and baseline weight category as factors.

Percentage of Participants achieving ≥75% Improve

Comparison groups

Placebo- Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

864

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[10]

Method

Regression, Logistic

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[10] - Logistic Regression analysis included treatment, geographic region, previous non-biologic systemic therapy and baseline weight category as factors.

Secondary: Percentage of Participants Achieving an sPGA of 0 (Efficacy of Ixekizumab in participants with moderate to severe plaque Ps Measure: sPGA)

Top of page

End point title

Percentage of Participants Achieving an sPGA of 0 (Efficacy of Ixekizumab in participants with moderate to severe plaque Ps Measure: sPGA)

End point description

End point type

Secondary

End point timeframe

Week 12

End point values	Placebo- Induction Period	Ixe Q4W Induction Period	Ixe Q2W - Induction Period
Number of subjects analysed	431 ^[11]	432 ^[12]	433 ^[13]
Units: percentage of participants
number (not applicable)	0.0	34.5	37.0

Notes
[11] - All randomized participants and non-responders for NRI analysis.
[12] - All randomized participants and non-responders for NRI analysis.
[13] - All randomized participants and non-responders for NRI analysis.

Percentage of Participants Achieving an sPGA of 0

Comparison groups

Placebo- Induction Period v Ixe Q4W Induction Period

Number of subjects included in analysis

863

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[14]

Method

Fisher exact

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[14] - Due to the zero count in placebo group, p-values from Logistic Regression were not obtainable, therefore the p-value is from Fisher's exact test.

Percentage of Participants Achieving an sPGA of 0

Comparison groups

Placebo- Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

864

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[15]

Method

Fisher exact

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[15] - Due to the zero count in placebo group, p-values from Logistic Regression were not obtainable, therefore the p-value is from Fisher's exact test

Secondary: Percentage of Participants Achieving PASI 90% (PASI90) or 100% (PASI100) (Efficacy of Ixekizumab in participants with moderate to severe plaque Ps Measure: PASI)

Top of page

End point title

Percentage of Participants Achieving PASI 90% (PASI90) or 100% (PASI100) (Efficacy of Ixekizumab in participants with moderate to severe plaque Ps 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 or PASI100 were defined as having an improvement of ≥90% or of 100% respectively in PASI scores compared to baseline.

End point type

Secondary

End point timeframe

Week 12

End point values	Placebo- Induction Period	Ixe Q4W Induction Period	Ixe Q2W - Induction Period
Number of subjects analysed	431 ^[16]	432 ^[17]	433 ^[18]
Units: percentage of participants
number (not applicable)
PASI90	0.5	64.6	70.9
PASI100	0.0	33.6	35.3

Notes
[16] - All randomized participants and non-responders for NRI analysis.
[17] - All randomized participants and non-responders for NRI analysis.
[18] - All randomized participants and non-responders for NRI analysis.

Percentage of Participants Achieving PASI 90%

Comparison groups

Placebo- Induction Period v Ixe Q4W Induction Period

Number of subjects included in analysis

863

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[19]

Method

Regression, Logistic

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[19] - P-value is for PASI90.

Percentage of Participants Achieving PASI 90%

Comparison groups

Placebo- Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

864

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[20]

Method

Regression, Logistic

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[20] - P-value is for PASI90.

Percentage of Participants Achieving PASI 90%

Comparison groups

Placebo- Induction Period v Ixe Q4W Induction Period

Number of subjects included in analysis

863

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[21]

Method

Fisher exact

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[21] - P-value is for PASI100.

Percentage of Participants Achieving PASI 90%

Comparison groups

Placebo- Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

864

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[22]

Method

Fisher exact

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[22] - P-value is for PASI100.

Secondary: Percentage of participants maintaining sPGA 0 or 1 after Re-Randomization at start of maintenance dosing period

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End point title

Percentage of participants maintaining sPGA 0 or 1 after Re-Randomization at start of maintenance dosing period

End point description

End point type

Secondary

End point timeframe

Week 60

End point values	Ixe/Placebo- Maintenance Period Primary Pop	Ixe/Ixe Q12W - Maintenance Period Primary Pop	Ixe/Ixe Q4W - Maintenance Period Primary Pop	Ixe/Placebo	Ixe/Q12W	Ixe/Q4W
Number of subjects analysed	226 ^[23]	227 ^[24]	227 ^[25]	226	227	229
Units: percentage of participants
number (not applicable)	7.5	37.4	72.9	7.5	37.4	72.9

Notes
[23] - All participants who received at least one dose of study drug and non-responders for NRI.
[24] - All participants who received at least one dose of study drug and non-responders for NRI.
[25] - All participants who received at least one dose of study drug and non-responders for NRI.

Percentage of participants maintaining sPGA 0 or 1

Comparison groups

Ixe/Placebo v Ixe/Q12W

Number of subjects included in analysis

453

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[26]

Method

Regression, Logistic

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[26] - Logistic Regression analysis included treatment and baseline weight category as factors.

Percentage of participants maintaining sPGA 0 or 1

Comparison groups

Ixe/Placebo v Ixe/Q4W

Number of subjects included in analysis

455

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[27]

Method

Regression, Logistic

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[27] - Logistic Regression analysis included treatment and baseline weight category as factors.

Secondary: Percentage of Participants with Itch Numeric Rating Scale (Itch NRS) Score ≥4 Point reduction from baseline

Top of page

End point title

Percentage of Participants with Itch Numeric Rating Scale (Itch NRS) Score ≥4 Point reduction from baseline

End point description

The Itch NRS is a participant-administered, 11-point horizontal scale anchored at 0 (no itch) and 10 (worst itch imaginable). Overall severity of a participant's itching from Ps is indicated by circling the number that best describes the worst level of itching in the past 24 hours.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo- Induction Period	Ixe Q4W Induction Period	Ixe Q2W - Induction Period
Number of subjects analysed	374 ^[28]	379 ^[29]	391 ^[30]
Units: percentage of participants
number (not applicable)	15.5	80.5	85.9

Notes
[28] - All randomized participants and non-responders for NRI analysis.
[29] - All randomized participants and non-responders for NRI analysis.
[30] - All randomized participants and non-responders for NRI analysis.

Percentage of Participants with Itch

Comparison groups

Placebo- Induction Period v Ixe Q4W Induction Period

Number of subjects included in analysis

753

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[31]

Method

Regression, Logistic

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[31] - Logistic Regression analysis included treatment, geographic region, previous non-biologic systemic therapy and baseline weight category as factors

Percentage of Participants with Itch

Comparison groups

Placebo- Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

765

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[32]

Method

Regression, Logistic

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[32] - Logistic Regression analysis included treatment, geographic region, previous non-biologic systemic therapy and baseline weight category as factors

Secondary: Change from baseline in Dermatology-Specific Quality of Life Index (DLQI) Score

Top of page

End point title

Change from baseline in Dermatology-Specific Quality of Life Index (DLQI) Score

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 unanswered ("not relevant") responses were scored as "0." Total scores range from 0 to 30, with higher score indicating greater quality of life is 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).

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo- Induction Period	Ixe Q4W Induction Period	Ixe Q2W - Induction Period
Number of subjects analysed	421 ^[33]	421 ^[34]	427 ^[35]
Units: units on a scale
least squares mean (standard error)	-1.0 ( 0.27 )	-10.7 ( 0.27 )	-11.1 ( 0.26 )

Notes
[33] - All randomized participants and those who had at least 1 post baseline measurement.
[34] - All randomized participants and those who had at least 1 post baseline measurement.
[35] - All randomized participants and those who had at least 1 post baseline measurement.

Change from baseline in DLQI Score

Comparison groups

Placebo- Induction Period v Ixe Q4W Induction Period

Number of subjects included in analysis

842

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[36]

Method

Mixed models analysis

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[36] - LS mean and P-value were calculated using MMRM with baseline score as a covariate, treatment, geographic region, previous non-biologic systemic therapy, baseline weight category, visit and treatment-by-visit interaction as fixed effects.

Change from baseline in DLQI Score

Comparison groups

Placebo- Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

848

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[37]

Method

Mixed models analysis

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[37] - LS mean and P-value were calculated using MMRM with baseline score as a covariate, treatment, geographic region, previous non-biologic systemic therapy, baseline weight category, visit and treatment-by-visit interaction as fixed effects.

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 is a numeric, reproducible, objective tool for evaluation of fingernail Ps. This scale is used to evaluate the severity of fingernail bed Ps and fingernail matrix Ps by area of involvement in the fingernail unit. The fingernail is divided with imaginary horizontal and longitudinal lines into quadrants. Each fingernail is given a score for fingernail bed Ps 0 (none) to 4 (Ps in 4 quadrants of the fingernail) and fingernail matrix Ps 0 (none) to 4 (Ps in 4 quadrants of the matrix), depending on the presence (score of 1) or absence (score of 0) of any of the features of fingernail bed or matrix Ps in each quadrant. The NAPSI score of a fingernail is the sum of scores in fingernail bed and fingernail matrix from each quadrant (maximum of 8). Each fingernail is evaluated, then the sum of all fingernails equals the total NAPSI score with a range from 0 to 80 with higher scores indicating more severe psoriasis. LS mean change from baseline was calculated using MMRM.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo- Induction Period	Ixe Q4W Induction Period	Ixe Q2W - Induction Period
Number of subjects analysed	280 ^[38]	276 ^[39]	279 ^[40]
Units: units on a scale
least squares mean (standard error)	2.17 ( 0.672 )	-7.19 ( 0.671 )	-7.24 ( 0.657 )

Notes
[38] - All randomized participants and those who had fingernail Ps at baseline.
[39] - All randomized participants and those who had fingernail Ps at baseline.
[40] - All randomized participants and those who had fingernail Ps at baseline.

Change from baseline in NAPSI

Comparison groups

Placebo- Induction Period v Ixe Q4W Induction Period

Number of subjects included in analysis

556

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[41]

Method

Mixed models analysis

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[41] - LS mean and P-value were calculated using MMRM with baseline score as a covariate, treatment, geographic region, previous non-biologic systemic therapy, baseline weight category, visit and treatment-by-visit interaction as fixed effects.

Change from baseline in NAPSI

Comparison groups

Placebo- Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

559

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[42]

Method

Mixed models analysis

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[42] - LS mean and P-value were calculated using MMRM with baseline score as a covariate, treatment, geographic region, previous non-biologic systemic therapy, baseline weight category, visit and treatment-by-visit interaction as fixed effects.

Secondary: Percent of Body Surface Area (BSA) involvement of Ps

Top of page

End point title

Percent of Body Surface Area (BSA) involvement of Ps

End point description

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 participants hand (includes the palm, fingers and thumb). Total BSA is the sum of handprints from the affected areas. LS mean change from baseline was calculated using MMRM.

End point type

Secondary

End point timeframe

Week 12

End point values	Placebo- Induction Period	Ixe Q4W Induction Period	Ixe Q2W - Induction Period
Number of subjects analysed	426 ^[43]	425 ^[44]	428 ^[45]
Units: percentage of body surface
least squares mean (standard error)	1.3 ( 0.67 )	-21.4 ( 0.67 )	-22.4 ( 0.66 )

Notes
[43] - All randomized participants and those who had at least 1 post-baseline BSA measurement.
[44] - All randomized participants and those who had at least 1 post-baseline BSA measurement.
[45] - All randomized participants and those who had at least 1 post-baseline BSA measurement.

Percent of Body Surface Area (BSA)

Comparison groups

Placebo- Induction Period v Ixe Q4W Induction Period

Number of subjects included in analysis

851

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[46]

Method

Mixed models analysis

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[46] - LS mean and P-value were calculated using MMRM with baseline score as a covariate, treatment, geographic region, previous non-biologic systemic therapy, baseline weight category, visit and treatment-by-visit interaction as fixed effects.

Percent of Body Surface Area (BSA)

Comparison groups

Placebo- Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

854

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[47]

Method

Mixed models analysis

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[47] - LS mean and P-value were calculated using MMRM with baseline score as a covariate, treatment, geographic region, previous non-biologic systemic therapy, baseline weight category, visit and treatment-by-visit interaction as fixed effects.

Secondary: Change from baseline in Psoriasis Scalp Severity Index (PSSI)

Top of page

End point title

Change from baseline in Psoriasis Scalp Severity Index (PSSI)

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 to 72, with lower scores indicating less severity. LS mean change from baseline was calculated using MMRM.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo- Induction Period	Ixe Q4W Induction Period	Ixe Q2W - Induction Period
Number of subjects analysed	393 ^[48]	413 ^[49]	393 ^[50]
Units: units on a scale
least squares mean (standard error)	-1.8 ( 0.53 )	-18.3 ( 0.52 )	-19.2 ( 0.52 )

Notes
[48] - All randomized participants and those who had scalp Ps at baseline.
[49] - All randomized participants and those who had scalp Ps at baseline.
[50] - All randomized participants and those who had scalp Ps at baseline.

Change from baseline in Psoriasis Scalp Severity

Comparison groups

Ixe Q4W Induction Period v Placebo- Induction Period

Number of subjects included in analysis

806

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[51]

Method

Mixed models analysis

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[51] - LS mean and P-value were calculated using MMRM with baseline score as a covariate, treatment, geographic region, previous non-biologic systemic therapy, baseline weight category, visit and treatment-by-visit interaction as fixed effects.

Change from baseline in Psoriasis Scalp Severity

Comparison groups

Placebo- Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

786

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[52]

Method

Mixed models analysis

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[52] - LS mean and P-value were calculated using MMRM with baseline score as a covariate, treatment, geographic region, previous non-biologic systemic therapy, baseline weight category, visit and treatment-by-visit interaction as fixed effects.

Secondary: Change from Baseline in all scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) (Quality of life and outcome assessments. Measures: Participant Reported Outcomes [PRO])

Top of page

End point title

Change from Baseline in all scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) (Quality of life and outcome assessments. Measures: Participant Reported Outcomes [PRO])

End point description

WPAI-PSO is a participant administered, 6-item instrument used to assess the impact of Ps on the productivity impairment within the past 7 days. WPAI-PSO has 4 domains: 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 (reduced productivity while at work), overall work impairment (absenteeism and presenteeism), and impairment in activities performed outside of work. Percentage is calculated as: each score * 100 with greater scores indicating greater impairment. LS mean change from baseline was calculated using analysis of covariance (ANCOVA).

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo- Induction Period	Ixe Q4W Induction Period	Ixe Q2W - Induction Period
Number of subjects analysed	420 ^[53]	417 ^[54]	427 ^[55]
Units: units on a scale
least squares mean (standard error)
Absenteeism	0.2 ( 0.88 )	-3.5 ( 0.87 )	-2.6 ( 0.84 )
Activity Impairment	0.8 ( 1.18 )	-24.5 ( 1.18 )	-25.2 ( 1.15 )
Presenteeism	0.5 ( 1.30 )	-18.8 ( 1.28 )	-18.3 ( 1.24 )
Work Productivity Loss	-0.8 ( 1.40 )	-20.6 ( 1.38 )	-19.8 ( 1.33 )

Notes
[53] - All randomized participants had results at specific timepoints, last observation carried forward.
[54] - All randomized participants had results at specific timepoints, last observation carried forward.
[55] - All randomized participants had results at specific timepoints, last observation carried forward.

Change from Baseline in all scores of the WPAI-PSO

Comparison groups

Placebo- Induction Period v Ixe Q4W Induction Period

Number of subjects included in analysis

837

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[56]

Method

ANCOVA

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[56] - The LS Mean and p-values were calculated using an ANCOVA model and included treatment, geographic region, previous non-biologic systemic therapy, baseline weight category, and baseline WPAI value.

Change from Baseline in all scores of the WPAI-PSO

Comparison groups

Placebo- Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

847

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.003 ^[57]

Method

ANCOVA

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[57] - The LS Mean and p-values were calculated using an ANCOVA model and included treatment, geographic region, previous non-biologic systemic therapy, baseline weight category, and baseline WPAI value.

Change from Baseline in all scores of the WPAI-PSO

Comparison groups

Placebo- Induction Period v Ixe Q4W Induction Period

Number of subjects included in analysis

837

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[58]

Method

ANCOVA

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[58] - The LS Mean and p-values were calculated using an ANCOVA model and included treatment, geographic region, previous non-biologic systemic therapy, baseline weight category, and baseline WPAI value.

Change from Baseline in all scores of the WPAI-PSO

Comparison groups

Placebo- Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

847

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[59]

Method

ANCOVA

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[59] - The LS Mean and p-values were calculated using an ANCOVA model and included treatment, geographic region, previous non-biologic systemic therapy, baseline weight category, and baseline WPAI value.

Change from Baseline in all scores of the WPAI-PSO

Comparison groups

Placebo- Induction Period v Ixe Q4W Induction Period

Number of subjects included in analysis

837

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[60]

Method

ANCOVA

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[60] - The LS Mean and p-values were calculated using an ANCOVA model and included treatment, geographic region, previous non-biologic systemic therapy, baseline weight category, and baseline WPAI value.

Change from Baseline in all scores of the WPAI-PSO

Comparison groups

Placebo- Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

847

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[61]

Method

ANCOVA

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[61] - The LS Mean and p-values were calculated using an ANCOVA model and included treatment, geographic region, previous non-biologic systemic therapy, baseline weight category, and baseline WPAI value.

Change from Baseline in all scores of the WPAI-PSO

Comparison groups

Placebo- Induction Period v Ixe Q4W Induction Period

Number of subjects included in analysis

837

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[62]

Method

ANCOVA

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[62] - The LS Mean and p-values were calculated using an ANCOVA model and included treatment, geographic region, previous non-biologic systemic therapy, baseline weight category, and baseline WPAI value.

Change from Baseline in all scores of the WPAI-PSO

Comparison groups

Placebo- Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

847

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[63]

Method

ANCOVA

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[63] - The LS Mean and p-values were calculated using an ANCOVA model and included treatment, geographic region, previous non-biologic systemic therapy, baseline weight category, and baseline WPAI value.

Secondary: Change from Baseline in Quick Inventory of Depressive Symptomatology-Self Reported 16 Items (QIDS-SR16)

Top of page

End point title

Change from Baseline in Quick Inventory of Depressive Symptomatology-Self Reported 16 Items (QIDS-SR16)

End point description

QIDS-SR16 is a participant-administered, 16-item instrument intended to assess the existence and severity of symptoms of depression. A participant is asked to consider each statement as it relates to the way they have felt for the past 7 days and rate each on a 4-point scale: 0 (best) to 3 (worst). The sum of the 16 items corresponding to 9 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] to give a single total scores range from 0 to 27, with higher scores indicating greater symptom severity. LS mean change from baseline was calculated using ANCOVA.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo- Induction Period	Ixe Q4W Induction Period	Ixe Q2W - Induction Period
Number of subjects analysed	421 ^[64]	417 ^[65]	423 ^[66]
Units: units on a scale
least squares mean (standard error)	-0.1 ( 0.17 )	-1.0 ( 0.17 )	-1.3 ( 0.17 )

Notes
[64] - All randomized participants and those that had results at the specified time points, LOCF.
[65] - All randomized participants and those that had results at the specified time points, LOCF.
[66] - All randomized participants and those that had results at the specified time points, LOCF.

Change from Baseline in QIDS-SR16

Comparison groups

Placebo- Induction Period v Ixe Q4W Induction Period

Number of subjects included in analysis

838

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[67]

Method

ANCOVA

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[67] - LS Mean and p-values were calculated using an ANCOVA model that included treatment, geographic region, previous non-biologic systemic therapy, baseline weight category, and baseline QIDS value in the model.

Change from Baseline in QIDS-SR16

Comparison groups

Placebo- Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

844

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[68]

Method

ANCOVA

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[68] - LS Mean and p-values were calculated using an ANCOVA model that included treatment, geographic region, previous non-biologic systemic therapy, baseline weight category, and baseline QIDS value in the model.

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 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 PCS and MCS scores. Scores range from 0 to 100, with higher scores indicating better levels of function and/or better health. LS mean change from baseline was calculated using ANCOVA.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo- Induction Period	Ixe Q4W Induction Period	Ixe Q2W - Induction Period
Number of subjects analysed	418 ^[69]	415 ^[70]	427 ^[71]
Units: units on a scale
least squares mean (standard error)
PCS	-0.1747 ( 0.4012 )	4.3081 ( 0.3990 )	4.3159 ( 0.3878 )
MCS	0.8729 ( 0.4638 )	3.7386 ( 0.4633 )	4.1293 ( 0.4480 )

Notes
[69] - All randomized participants and those with results at the specified time points, LOCF.
[70] - All randomized participants and those with results at the specified time points, LOCF.
[71] - All randomized participants and those with results at the specified time points, LOCF.

Change from baseline in SF-36

Comparison groups

Ixe Q4W Induction Period v Placebo- Induction Period

Number of subjects included in analysis

833

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[72]

Method

ANCOVA

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[72] - The LS Mean and p-values were calculated using an ANCOVA model and included treatment, geographic region, previous non-biologic systemic therapy, baseline weight category, and baseline SF-36 value in the model.

Change from baseline in SF-36

Comparison groups

Placebo- Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

845

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[73]

Method

ANCOVA

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[73] - The LS Mean and p-values were calculated using an ANCOVA model and included treatment, geographic region, previous non-biologic systemic therapy, baseline weight category, and baseline SF-36 value in the model.

Change from baseline in SF-36

Comparison groups

Placebo- Induction Period v Ixe Q4W Induction Period

Number of subjects included in analysis

833

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[74]

Method

ANCOVA

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[74] - The LS Mean and p-values were calculated using an ANCOVA model and included treatment, geographic region, previous non-biologic systemic therapy, baseline weight category, and baseline SF-36 value in the model.

Change from baseline in SF-36

Comparison groups

Ixe Q2W - Induction Period v Placebo- Induction Period

Number of subjects included in analysis

845

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[75]

Method

ANCOVA

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[75] - The LS Mean and p-values were calculated using an ANCOVA model and included treatment, geographic region, previous non-biologic systemic therapy, baseline weight category, and baseline SF-36 value in the model.

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

Top of page

End point title

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

End point description

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). LS mean change from baseline calculated using MMRM.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo- Induction Period	Ixe Q4W Induction Period	Ixe Q2W - Induction Period
Number of subjects analysed	424 ^[76]	425 ^[77]	427 ^[78]
Units: units on a scale
least squares mean (standard error)	-0.2 ( 0.06 )	-3.1 ( 0.06 )	-3.2 ( 0.06 )

Notes
[76] - All randomized participants and those with at least 1 poste-baseline PatGA.
[77] - All randomized participants and those with at least 1 poste-baseline PatGA.
[78] - All randomized participants and those with at least 1 poste-baseline PatGA.

Change from baseline in PatGA

Comparison groups

Placebo- Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

851

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[79]

Method

Mixed models analysis

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[79] - LS mean and P-value were calculated using MMRM with baseline score as a covariate, treatment, geographic region, previous non-biologic systemic therapy, baseline weight category, visit and treatment-by-visit interaction as fixed effects.

Change from baseline in PatGA

Comparison groups

Placebo- Induction Period v Ixe Q4W Induction Period

Number of subjects included in analysis

849

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[80]

Method

Mixed models analysis

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[80] - LS mean and P-value were calculated using MMRM with baseline score as a covariate, treatment, geographic region, previous non-biologic systemic therapy, baseline weight category, visit and treatment-by-visit interaction as fixed effects.

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

Top of page

End point title

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

End point description

The Palmoplantar PASI is a composite score derived from the sum of scores for erythema, induration, and desquamation [scores range from 0 (none) to 4 (very severe) for each] multiplied by the score for the extent of palm and sole area involvement [scores range from 0 (0%) to 6 (90 to100%)], with a total scores range from 0 to 72. Participants achieving PPASI50, PPASI75 or PASI100 were defined as having an improvement of at least 50%, 90%, or of 100%, respectively, in the PPASI scores compared to baseline.

End point type

Secondary

End point timeframe

Week 12

End point values	Placebo- Induction Period	Ixe Q4W Induction Period	Ixe Q2W - Induction Period
Number of subjects analysed	133 ^[81]	131 ^[82]	140 ^[83]
Units: percentage of participants
number (not applicable)
PPASI50	35.3	84.0	82.9
PPASI75	26.3	74.8	77.1
PPASI100	20.3	65.6	70.0

Notes
[81] - All randomized participants and those who had palmoplantar Ps at baseline.
[82] - All randomized participants and those who had palmoplantar Ps at baseline.
[83] - All randomized participants and those who had palmoplantar Ps at baseline.

Percentage of Participants achieving PPASI

Comparison groups

Ixe Q4W Induction Period v Placebo- Induction Period

Number of subjects included in analysis

264

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[84]

Method

Regression, Logistic

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[84] - P-value is for PPASI50.

Percentage of Participants achieving PPASI

Comparison groups

Placebo- Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

273

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[85]

Method

Regression, Logistic

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[85] - P-value is for PPASI50.

Percentage of Participants achieving PPASI

Comparison groups

Placebo- Induction Period v Ixe Q4W Induction Period

Number of subjects included in analysis

264

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[86]

Method

Regression, Logistic

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[86] - P-value is for PPASI75

Percentage of Participants achieving PPASI

Comparison groups

Placebo- Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

273

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[87]

Method

Regression, Logistic

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[87] - P-value is for PPASI75

Percentage of Participants achieving PPASI

Comparison groups

Placebo- Induction Period v Ixe Q4W Induction Period

Number of subjects included in analysis

264

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[88]

Method

Regression, Logistic

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[88] - P-value is for PPASI100

Percentage of Participants achieving PPASI

Comparison groups

Placebo- Induction Period v Ixe Q2W - Induction Period

Number of subjects included in analysis

273

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[89]

Method

Regression, Logistic

Confidence interval

sides

2-sided

lower limit

upper limit

Notes
[89] - P-value if for PPASI100.

Secondary: Pharmacokinetics (PK): Trough concentration at steady state (Ctrough ss)

Top of page

End point title

Pharmacokinetics (PK): Trough concentration at steady state (Ctrough ss)

End point description

End point type

Secondary

End point timeframe

Weeks 12: Day 84 and Week 24: Day 168

End point values	Ixe Q4W - Maintenance Period	Ixe Q12W - Maintenance Period	Ixe Q2W	IxeQ4W
Number of subjects analysed	223 ^[90]	60 ^[91]	192 ^[92]	215 ^[93]
Units: micrograms/milliliter (µg/mL)
geometric mean (geometric coefficient of variation)
Week 12	0 ( 0 )	0 ( 0 )	7.73 ( 79 )	2.94 ( 89 )
Week 24	2.36 ( 111 )	0.281 ( 175 )	0 ( 0 )	0 ( 0 )

Notes
[90] - Geometric coefficient of variation is presented as a percent.
[91] - Geometric coefficient of variation is presented as a percent.
[92] - Geometric coefficient of variation is presented as a percent.
[93] - Geometric coefficient of variation is presented as a percent.

No statistical analyses for this end point

Secondary: Percentage of Participants with Anti-ixekizumab antibodies

Top of page

End point title

Percentage of Participants with Anti-ixekizumab antibodies

End point description

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

End point type

Secondary

End point timeframe

Baseline through Week 12

End point values	Placebo- Induction Period	Ixe Q4W Induction Period	Ixe Q2W - Induction Period
Number of subjects analysed	431 ^[94]	432 ^[95]	433 ^[96]
Units: percentage of participants
number (not applicable)	0.5	12.5	10.3

Notes
[94] - All randomized participants who received at least 1 dose of study drug and had evaluable data.
[95] - All randomized participants who received at least 1 dose of study drug and had evaluable data.
[96] - All randomized participants who received at least 1 dose of study drug 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-RHAZ

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

21.1

Reporting group title

PBO-induction period

Reporting group description

Reporting group title

IXE80Q4W-induction period

Reporting group description

Reporting group title

IXE80Q2W-induction period

Reporting group description

Reporting group title

IXE/PBO-maintenance primary population

Reporting group description

Reporting group title

IXE/IXE80Q12W-maintenance primary population

Reporting group description

Reporting group title

IXE/IXE80Q4W-maintenance primary population

Reporting group description

Reporting group title

PBOResp/PBO-maintenance secondary population

Reporting group description

Reporting group title

PBONonR/IXE80Q4W-maintenance secondary population

Reporting group description

Reporting group title

IXE80Q4WNonR/IXE80Q4W-maintenance secondary population

Reporting group description

Reporting group title

IXE80Q2WNonR/IXE80Q4W-maintenance secondary population

Reporting group description

Reporting group title

IXE80Q4W-maintenance relapse population

Reporting group description

Reporting group title

PBO-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

PBO-follow-up period

Reporting group description

Reporting group title

IXE80Q2W-follow-up period

Reporting group description

Reporting group title

IXE80Q4W-follow-up period

Reporting group description

Reporting group title

IXE80Q12W-follow-up period

Reporting group description

PBO-induction period

IXE80Q4W-induction period

IXE80Q2W-induction period

IXE/PBO-maintenance primary population

IXE/IXE80Q12W-maintenance primary population

IXE/IXE80Q4W-maintenance primary population

PBOResp/PBO-maintenance secondary population

PBONonR/IXE80Q4W-maintenance secondary population

IXE80Q4WNonR/IXE80Q4W-maintenance secondary population

IXE80Q2WNonR/IXE80Q4W-maintenance secondary population

IXE80Q4W-maintenance relapse population

PBO-long term extension period

IXE-long term extension period

Total IXE-long term extension period

PBO-follow-up period

IXE80Q2W-follow-up period

IXE80Q4W-follow-up period

IXE80Q12W-follow-up period

Total subjects affected by serious adverse events

subjects affected / exposed

5 / 431 (1.16%)

12 / 432 (2.78%)

7 / 433 (1.62%)

7 / 226 (3.10%)

11 / 227 (4.85%)

14 / 229 (6.11%)

0 / 16 (0.00%)

24 / 391 (6.14%)

8 / 78 (10.26%)

3 / 62 (4.84%)

11 / 348 (3.16%)

1 / 26 (3.85%)

134 / 1054 (12.71%)

134 / 1075 (12.47%)

2 / 18 (11.11%)

6 / 285 (2.11%)

13 / 700 (1.86%)

0 / 25 (0.00%)

number of deaths (all causes)

number of deaths resulting from adverse events

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

adrenal adenoma

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

1 / 78 (1.28%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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

b-cell lymphoma

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

1 / 391 (0.26%)

1 / 78 (1.28%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

basal cell carcinoma

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cholangiocarcinoma

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

1 / 700 (0.14%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

colon cancer

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

1 / 391 (0.26%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

1 / 700 (0.14%)

0 / 25 (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

diffuse large b-cell lymphoma

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

hypopharyngeal cancer

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

1 / 431 (0.23%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

intraductal proliferative breast lesion

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

invasive ductal breast carcinoma

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

1 / 432 (0.23%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

2 / 1054 (0.19%)

2 / 1075 (0.19%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

laryngeal squamous cell carcinoma

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

lipoma

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

lung cancer metastatic

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

2 / 1054 (0.19%)

2 / 1075 (0.19%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

2 / 2

0 / 0

lung neoplasm malignant

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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 21.1

subjects affected / exposed ^[1]

0 / 303 (0.00%)

0 / 289 (0.00%)

0 / 291 (0.00%)

0 / 154 (0.00%)

0 / 150 (0.00%)

0 / 156 (0.00%)

0 / 10 (0.00%)

0 / 276 (0.00%)

0 / 54 (0.00%)

0 / 41 (0.00%)

0 / 241 (0.00%)

0 / 15 (0.00%)

1 / 731 (0.14%)

1 / 743 (0.13%)

0 / 13 (0.00%)

0 / 207 (0.00%)

0 / 485 (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

pyogenic granuloma

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

1 / 285 (0.35%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

rectal cancer

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

renal cell carcinoma

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

squamous cell carcinoma of lung

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

1 / 391 (0.26%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

thyroid adenoma

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

circulatory collapse

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

1 / 391 (0.26%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

1 / 227 (0.44%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

femoral artery aneurysm

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

hypertension

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

3 / 1054 (0.28%)

3 / 1075 (0.28%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

3 / 6

0 / 0

deaths causally related to treatment / all

0 / 0

hypotension

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

1 / 285 (0.35%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

peripheral artery occlusion

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

shock

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

subclavian vein thrombosis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

varicose vein

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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

bile duct stent insertion

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

1 / 700 (0.14%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cholecystectomy

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

2 / 700 (0.29%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

duodenal sphincterotomy

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

1 / 700 (0.14%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

hernia hiatus repair

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pancreaticoduodenectomy

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

1 / 700 (0.14%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

tonsillectomy

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ureteral stent insertion

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

varicose vein operation

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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 21.1

subjects affected / exposed ^[2]

0 / 128 (0.00%)

0 / 143 (0.00%)

0 / 142 (0.00%)

0 / 72 (0.00%)

0 / 77 (0.00%)

0 / 73 (0.00%)

0 / 6 (0.00%)

0 / 115 (0.00%)

0 / 24 (0.00%)

0 / 21 (0.00%)

0 / 107 (0.00%)

0 / 11 (0.00%)

1 / 323 (0.31%)

1 / 332 (0.30%)

0 / 5 (0.00%)

0 / 78 (0.00%)

0 / 215 (0.00%)

0 / 15 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

hellp syndrome

alternative dictionary used: MedDRA 21.1

subjects affected / exposed ^[3]

0 / 128 (0.00%)

0 / 143 (0.00%)

0 / 142 (0.00%)

0 / 72 (0.00%)

0 / 77 (0.00%)

0 / 73 (0.00%)

0 / 6 (0.00%)

0 / 115 (0.00%)

0 / 24 (0.00%)

0 / 21 (0.00%)

0 / 107 (0.00%)

0 / 11 (0.00%)

0 / 323 (0.00%)

0 / 332 (0.00%)

0 / 5 (0.00%)

0 / 78 (0.00%)

1 / 215 (0.47%)

0 / 15 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pre-eclampsia

alternative dictionary used: MedDRA 21.1

subjects affected / exposed ^[4]

0 / 128 (0.00%)

0 / 143 (0.00%)

0 / 142 (0.00%)

0 / 72 (0.00%)

0 / 77 (0.00%)

0 / 73 (0.00%)

0 / 6 (0.00%)

0 / 115 (0.00%)

0 / 24 (0.00%)

0 / 21 (0.00%)

0 / 107 (0.00%)

0 / 11 (0.00%)

0 / 323 (0.00%)

0 / 332 (0.00%)

0 / 5 (0.00%)

0 / 78 (0.00%)

1 / 215 (0.47%)

0 / 15 (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

death

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

1 / 229 (0.44%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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

drug withdrawal syndrome

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

fatigue

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

1 / 348 (0.29%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

non-cardiac chest pain

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

1 / 391 (0.26%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Immune system disorders

drug hypersensitivity

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

1 / 433 (0.23%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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

cystocele

alternative dictionary used: MedDRA 21.1

subjects affected / exposed ^[5]

0 / 128 (0.00%)

0 / 143 (0.00%)

0 / 142 (0.00%)

0 / 72 (0.00%)

0 / 77 (0.00%)

0 / 73 (0.00%)

0 / 6 (0.00%)

0 / 115 (0.00%)

0 / 24 (0.00%)

0 / 21 (0.00%)

0 / 107 (0.00%)

0 / 11 (0.00%)

1 / 323 (0.31%)

1 / 332 (0.30%)

0 / 5 (0.00%)

0 / 78 (0.00%)

0 / 215 (0.00%)

0 / 15 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

endometriosis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed ^[6]

0 / 128 (0.00%)

0 / 143 (0.00%)

0 / 142 (0.00%)

0 / 72 (0.00%)

0 / 77 (0.00%)

0 / 73 (0.00%)

0 / 6 (0.00%)

0 / 115 (0.00%)

0 / 24 (0.00%)

0 / 21 (0.00%)

0 / 107 (0.00%)

0 / 11 (0.00%)

1 / 323 (0.31%)

1 / 332 (0.30%)

0 / 5 (0.00%)

0 / 78 (0.00%)

0 / 215 (0.00%)

0 / 15 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ovarian cyst

alternative dictionary used: MedDRA 21.1

subjects affected / exposed ^[7]

0 / 128 (0.00%)

0 / 143 (0.00%)

0 / 142 (0.00%)

0 / 72 (0.00%)

0 / 77 (0.00%)

0 / 73 (0.00%)

0 / 6 (0.00%)

0 / 115 (0.00%)

0 / 24 (0.00%)

0 / 21 (0.00%)

1 / 107 (0.93%)

0 / 11 (0.00%)

2 / 323 (0.62%)

2 / 332 (0.60%)

0 / 5 (0.00%)

0 / 78 (0.00%)

0 / 215 (0.00%)

0 / 15 (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

rectocele

alternative dictionary used: MedDRA 21.1

subjects affected / exposed ^[8]

0 / 128 (0.00%)

0 / 143 (0.00%)

0 / 142 (0.00%)

0 / 72 (0.00%)

0 / 77 (0.00%)

0 / 73 (0.00%)

0 / 6 (0.00%)

0 / 115 (0.00%)

0 / 24 (0.00%)

0 / 21 (0.00%)

0 / 107 (0.00%)

0 / 11 (0.00%)

1 / 323 (0.31%)

1 / 332 (0.30%)

0 / 5 (0.00%)

0 / 78 (0.00%)

0 / 215 (0.00%)

0 / 15 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

asthma

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

1 / 229 (0.44%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

chronic obstructive pulmonary disease

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

1 / 431 (0.23%)

1 / 432 (0.23%)

0 / 433 (0.00%)

1 / 226 (0.44%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

1 / 391 (0.26%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

2 / 1054 (0.19%)

2 / 1075 (0.19%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 2

0 / 1

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

0 / 7

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

dyspnoea

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pleurisy

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

1 / 226 (0.44%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

1 / 227 (0.44%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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

respiratory failure

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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

Psychiatric disorders

alcohol withdrawal syndrome

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

mood swings

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

1 / 348 (0.29%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

2 / 1054 (0.19%)

2 / 1075 (0.19%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

suicide attempt

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

3 / 1054 (0.28%)

3 / 1075 (0.28%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Product issues

device dislocation

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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 stenosis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

1 / 700 (0.14%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cholecystitis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

1 / 433 (0.23%)

0 / 226 (0.00%)

0 / 227 (0.00%)

1 / 229 (0.44%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

2 / 1054 (0.19%)

2 / 1075 (0.19%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

cholecystitis acute

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cholelithiasis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

1 / 431 (0.23%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

1 / 227 (0.44%)

1 / 229 (0.44%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

drug-induced liver injury

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

2 / 1054 (0.19%)

2 / 1075 (0.19%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

hepatitis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Investigations

cardiac electrophysiologic study

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

catheterisation cardiac

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

endoscopic retrograde cholangiopancreatography

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

1 / 700 (0.14%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

alcohol poisoning

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

1 / 229 (0.44%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ankle fracture

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

bone contusion

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

1 / 348 (0.29%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

1 / 226 (0.44%)

0 / 227 (0.00%)

1 / 229 (0.44%)

0 / 16 (0.00%)

1 / 391 (0.26%)

0 / 78 (0.00%)

0 / 62 (0.00%)

1 / 348 (0.29%)

1 / 26 (3.85%)

2 / 1054 (0.19%)

2 / 1075 (0.19%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

fibula fracture

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

1 / 26 (3.85%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

humerus fracture

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

1 / 226 (0.44%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

intentional overdose

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

limb injury

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

muscle rupture

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

post procedural complication

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

radius fracture

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

1 / 229 (0.44%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

spinal compression fracture

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

1 / 391 (0.26%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

tibia fracture

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

upper limb fracture

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

1 / 229 (0.44%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

wrist fracture

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

1 / 229 (0.44%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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

congenital ectopic pancreas

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

1 / 229 (0.44%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

congenital pyelocaliectasis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

1 / 78 (1.28%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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 coronary syndrome

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

2 / 1054 (0.19%)

2 / 1075 (0.19%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

acute myocardial infarction

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

1 / 432 (0.23%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

1 / 229 (0.44%)

0 / 16 (0.00%)

1 / 391 (0.26%)

0 / 78 (0.00%)

0 / 62 (0.00%)

1 / 348 (0.29%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

angina pectoris

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

3 / 391 (0.77%)

0 / 78 (0.00%)

0 / 62 (0.00%)

1 / 348 (0.29%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 4

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

angina unstable

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

arteriospasm coronary

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

1 / 62 (1.61%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

atrial fibrillation

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

1 / 391 (0.26%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

3 / 1054 (0.28%)

3 / 1075 (0.28%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

atrioventricular block first degree

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

1 / 432 (0.23%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

bradycardia

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

1 / 226 (0.44%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cardiac failure congestive

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

2 / 1054 (0.19%)

2 / 1075 (0.19%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

cardiogenic shock

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

1 / 229 (0.44%)

0 / 16 (0.00%)

1 / 391 (0.26%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

3 / 1054 (0.28%)

3 / 1075 (0.28%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

0 / 4

0 / 0

deaths causally related to treatment / all

0 / 0

coronary artery occlusion

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

1 / 227 (0.44%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

coronary artery stenosis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

1 / 227 (0.44%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

mitral valve incompetence

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

1 / 78 (1.28%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

1 / 229 (0.44%)

0 / 16 (0.00%)

1 / 391 (0.26%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

4 / 1054 (0.38%)

4 / 1075 (0.37%)

0 / 18 (0.00%)

1 / 285 (0.35%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

0 / 4

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

palpitations

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

stress cardiomyopathy

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

1 / 391 (0.26%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

supraventricular tachycardia

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

1 / 391 (0.26%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

tachycardia paroxysmal

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ventricular hypokinesia

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

carotid artery stenosis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

1 / 226 (0.44%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cerebral infarction

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

encephalopathy

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

1 / 227 (0.44%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

epilepsy

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

1 / 432 (0.23%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

intracranial aneurysm

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ischaemic stroke

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

1 / 348 (0.29%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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

lacunar infarction

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

1 / 18 (5.56%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

lumbar radiculopathy

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

1 / 433 (0.23%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

meralgia paraesthetica

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

1 / 78 (1.28%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

migraine

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

multiple sclerosis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

1 / 227 (0.44%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

parkinson's disease

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

1 / 226 (0.44%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

1 / 348 (0.29%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

presyncope

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

seizure

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

subarachnoid haemorrhage

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

vascular encephalopathy

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

2 / 1054 (0.19%)

2 / 1075 (0.19%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

leukopenia

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

lymphadenopathy

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ear and labyrinth disorders

tinnitus

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

1 / 62 (1.61%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

vertigo

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

vertigo positional

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Eye disorders

retinal detachment

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

1 / 432 (0.23%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 4

0 / 0

deaths causally related to treatment / all

0 / 0

retinal haemorrhage

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

abdominal adhesions

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

abdominal pain upper

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

1 / 78 (1.28%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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

acute abdomen

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

1 / 700 (0.14%)

0 / 25 (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 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

1 / 391 (0.26%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

chronic gastrointestinal bleeding

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

colitis ischaemic

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

1 / 432 (0.23%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

1 / 391 (0.26%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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

colitis ulcerative

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

1 / 285 (0.35%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

crohn's disease

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

1 / 432 (0.23%)

0 / 433 (0.00%)

1 / 226 (0.44%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

1 / 348 (0.29%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

1 / 700 (0.14%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 0

0 / 3

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

diarrhoea

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

enteritis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

1 / 348 (0.29%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

gastric ulcer

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

1 / 62 (1.61%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

gastrointestinal haemorrhage

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

1 / 78 (1.28%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

gastrooesophageal reflux disease

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

1 / 78 (1.28%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

haemorrhoids

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

2 / 1054 (0.19%)

2 / 1075 (0.19%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

inguinal hernia

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

1 / 227 (0.44%)

1 / 229 (0.44%)

0 / 16 (0.00%)

1 / 391 (0.26%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

3 / 1054 (0.28%)

3 / 1075 (0.28%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 4

0 / 0

deaths causally related to treatment / all

0 / 0

large intestinal obstruction

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pancreatitis relapsing

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

1 / 229 (0.44%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

rectal haemorrhage

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

1 / 285 (0.35%)

0 / 700 (0.00%)

0 / 25 (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 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

umbilical hernia

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

3 / 1054 (0.28%)

3 / 1075 (0.28%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 4

0 / 0

deaths causally related to treatment / all

0 / 0

upper gastrointestinal haemorrhage

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

1 / 226 (0.44%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

1 / 391 (0.26%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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

Skin and subcutaneous tissue disorders

dermatitis contact

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

1 / 391 (0.26%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

drug eruption

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

1 / 431 (0.23%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

drug reaction with eosinophilia and systemic symptoms

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

psoriasis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

1 / 348 (0.29%)

0 / 26 (0.00%)

2 / 1054 (0.19%)

2 / 1075 (0.19%)

0 / 18 (0.00%)

2 / 285 (0.70%)

1 / 700 (0.14%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 2

0 / 0

0 / 2

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pustular psoriasis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

1 / 432 (0.23%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

1 / 700 (0.14%)

0 / 25 (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

urticaria

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

1 / 433 (0.23%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

1 / 391 (0.26%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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

glomerulonephritis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

1 / 391 (0.26%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

nephrolithiasis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

1 / 227 (0.44%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

1 / 348 (0.29%)

0 / 26 (0.00%)

3 / 1054 (0.28%)

3 / 1075 (0.28%)

0 / 18 (0.00%)

0 / 285 (0.00%)

1 / 700 (0.14%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

0 / 4

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

renal colic

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

1 / 348 (0.29%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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

urinary incontinence

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

1 / 226 (0.44%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

1 / 348 (0.29%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Endocrine disorders

hyperparathyroidism

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

thyroid mass

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

1 / 700 (0.14%)

0 / 25 (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

bone pain

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

exostosis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

intervertebral disc degeneration

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

1 / 391 (0.26%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

1 / 227 (0.44%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

1 / 391 (0.26%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

1 / 700 (0.14%)

0 / 25 (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

osteoarthritis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

1 / 229 (0.44%)

0 / 16 (0.00%)

1 / 391 (0.26%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

4 / 1054 (0.38%)

4 / 1075 (0.37%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 5

0 / 0

deaths causally related to treatment / all

0 / 0

pain in extremity

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

rhabdomyolysis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

rotator cuff syndrome

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

1 / 229 (0.44%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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

spinal pain

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

1 / 348 (0.29%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

1 / 229 (0.44%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

appendicitis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

1 / 433 (0.23%)

0 / 226 (0.00%)

1 / 227 (0.44%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 4

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cellulitis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

1 / 432 (0.23%)

1 / 433 (0.23%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

2 / 391 (0.51%)

1 / 78 (1.28%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

4 / 1054 (0.38%)

4 / 1075 (0.37%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 2

0 / 1

0 / 0

2 / 4

0 / 0

deaths causally related to treatment / all

0 / 0

cellulitis pharyngeal

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

cellulitis staphylococcal

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

1 / 700 (0.14%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

chronic sinusitis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

1 / 700 (0.14%)

0 / 25 (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

chronic tonsillitis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

1 / 433 (0.23%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

clostridial sepsis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

1 / 391 (0.26%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

clostridium difficile colitis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

1 / 391 (0.26%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cystitis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cystitis bacterial

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

device related infection

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

1 / 391 (0.26%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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

ear infection

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

endometritis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed ^[9]

0 / 128 (0.00%)

0 / 143 (0.00%)

0 / 142 (0.00%)

0 / 72 (0.00%)

0 / 77 (0.00%)

0 / 73 (0.00%)

0 / 6 (0.00%)

0 / 115 (0.00%)

0 / 24 (0.00%)

0 / 21 (0.00%)

0 / 107 (0.00%)

0 / 11 (0.00%)

0 / 323 (0.00%)

0 / 332 (0.00%)

1 / 5 (20.00%)

0 / 78 (0.00%)

0 / 215 (0.00%)

0 / 15 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

epiglottitis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

gallbladder empyema

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

1 / 700 (0.14%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

gastroenteritis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

1 / 391 (0.26%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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

gastroenteritis viral

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

gastrointestinal bacterial infection

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

herpes zoster

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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 21.1

subjects affected / exposed

1 / 431 (0.23%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

injection site cellulitis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

1 / 432 (0.23%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

laryngitis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

lower respiratory tract infection

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

meningitis aseptic

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

osteomyelitis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

osteomyelitis chronic

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

peritonitis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

1 / 433 (0.23%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

peritonsillar abscess

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pilonidal cyst

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

1 / 226 (0.44%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

pneumonia

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

1 / 432 (0.23%)

0 / 433 (0.00%)

1 / 226 (0.44%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

5 / 1054 (0.47%)

5 / 1075 (0.47%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

1 / 5

0 / 0

deaths causally related to treatment / all

0 / 0

postoperative wound infection

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

1 / 229 (0.44%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

1 / 285 (0.35%)

0 / 700 (0.00%)

0 / 25 (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

pyelonephritis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

2 / 1054 (0.19%)

2 / 1075 (0.19%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

rectal abscess

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

1 / 391 (0.26%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

sinusitis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

1 / 391 (0.26%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

staphylococcal bacteraemia

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

2 / 1054 (0.19%)

2 / 1075 (0.19%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

staphylococcal infection

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

1 / 391 (0.26%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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

staphylococcal osteomyelitis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

1 / 391 (0.26%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

subcutaneous abscess

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

1 / 229 (0.44%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

3 / 1054 (0.28%)

3 / 1075 (0.28%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

tonsillitis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

3 / 1054 (0.28%)

3 / 1075 (0.28%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 5

0 / 0

deaths causally related to treatment / all

0 / 0

tonsillitis bacterial

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

1 / 432 (0.23%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

tooth abscess

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

urinary tract infection

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

2 / 1054 (0.19%)

2 / 1075 (0.19%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

urosepsis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

viral rash

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

0 / 1054 (0.00%)

0 / 1075 (0.00%)

0 / 18 (0.00%)

1 / 285 (0.35%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Metabolism and nutrition disorders

acidosis

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

dehydration

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

3 / 1054 (0.28%)

3 / 1075 (0.28%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

diabetes mellitus

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

hyperkalaemia

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

0 / 227 (0.00%)

0 / 229 (0.00%)

0 / 16 (0.00%)

0 / 391 (0.00%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

type 2 diabetes mellitus

alternative dictionary used: MedDRA 21.1

subjects affected / exposed

0 / 431 (0.00%)

0 / 432 (0.00%)

0 / 433 (0.00%)

0 / 226 (0.00%)

1 / 227 (0.44%)

0 / 229 (0.00%)

0 / 16 (0.00%)

1 / 391 (0.26%)

0 / 78 (0.00%)

0 / 62 (0.00%)

0 / 348 (0.00%)

0 / 26 (0.00%)

1 / 1054 (0.09%)

1 / 1075 (0.09%)

0 / 18 (0.00%)

0 / 285 (0.00%)

0 / 700 (0.00%)

0 / 25 (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

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.

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

Non-serious adverse events	PBO-induction period	IXE80Q4W-induction period	IXE80Q2W-induction period	IXE/PBO-maintenance primary population	IXE/IXE80Q12W-maintenance primary population	IXE/IXE80Q4W-maintenance primary population	PBOResp/PBO-maintenance secondary population	PBONonR/IXE80Q4W-maintenance secondary population	IXE80Q4WNonR/IXE80Q4W-maintenance secondary population	IXE80Q2WNonR/IXE80Q4W-maintenance secondary population	IXE80Q4W-maintenance relapse population	PBO-long term extension period	IXE-long term extension period	Total IXE-long term extension period	PBO-follow-up period	IXE80Q2W-follow-up period	IXE80Q4W-follow-up period	IXE80Q12W-follow-up period
Total subjects affected by non serious adverse events
subjects affected / exposed	128 / 431 (29.70%)	159 / 432 (36.81%)	170 / 433 (39.26%)	83 / 226 (36.73%)	122 / 227 (53.74%)	115 / 229 (50.22%)	8 / 16 (50.00%)	211 / 391 (53.96%)	55 / 78 (70.51%)	34 / 62 (54.84%)	114 / 348 (32.76%)	8 / 26 (30.77%)	414 / 1054 (39.28%)	414 / 1075 (38.51%)	3 / 18 (16.67%)	15 / 285 (5.26%)	33 / 700 (4.71%)	2 / 25 (8.00%)
Investigations
blood glucose increased
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	1 / 431 (0.23%)	0 / 432 (0.00%)	0 / 433 (0.00%)	0 / 226 (0.00%)	0 / 227 (0.00%)	1 / 229 (0.44%)	1 / 16 (6.25%)	2 / 391 (0.51%)	0 / 78 (0.00%)	0 / 62 (0.00%)	0 / 348 (0.00%)	0 / 26 (0.00%)	7 / 1054 (0.66%)	7 / 1075 (0.65%)	0 / 18 (0.00%)	0 / 285 (0.00%)	0 / 700 (0.00%)	0 / 25 (0.00%)
occurrences all number	1	0	0	0	0	1	1	4	0	0	0	0	7	7	0	0	0	0
electrocardiogram qt prolonged
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	0 / 431 (0.00%)	0 / 432 (0.00%)	0 / 433 (0.00%)	0 / 226 (0.00%)	0 / 227 (0.00%)	1 / 229 (0.44%)	1 / 16 (6.25%)	1 / 391 (0.26%)	0 / 78 (0.00%)	0 / 62 (0.00%)	0 / 348 (0.00%)	0 / 26 (0.00%)	1 / 1054 (0.09%)	1 / 1075 (0.09%)	0 / 18 (0.00%)	1 / 285 (0.35%)	0 / 700 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	0	0	0	0	1	1	1	0	0	0	0	1	1	0	1	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
skin papilloma
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	2 / 431 (0.46%)	4 / 432 (0.93%)	1 / 433 (0.23%)	2 / 226 (0.88%)	5 / 227 (2.20%)	2 / 229 (0.87%)	1 / 16 (6.25%)	4 / 391 (1.02%)	1 / 78 (1.28%)	0 / 62 (0.00%)	0 / 348 (0.00%)	0 / 26 (0.00%)	10 / 1054 (0.95%)	10 / 1075 (0.93%)	0 / 18 (0.00%)	0 / 285 (0.00%)	0 / 700 (0.00%)	0 / 25 (0.00%)
occurrences all number	2	4	1	3	6	2	1	6	1	0	0	0	14	14	0	0	0	0
Injury, poisoning and procedural complications
foreign body in eye
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	0 / 431 (0.00%)	0 / 432 (0.00%)	0 / 433 (0.00%)	0 / 226 (0.00%)	0 / 227 (0.00%)	0 / 229 (0.00%)	1 / 16 (6.25%)	0 / 391 (0.00%)	0 / 78 (0.00%)	0 / 62 (0.00%)	0 / 348 (0.00%)	0 / 26 (0.00%)	1 / 1054 (0.09%)	1 / 1075 (0.09%)	0 / 18 (0.00%)	0 / 285 (0.00%)	0 / 700 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	1	1	0	0	0	0
Nervous system disorders
headache
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	15 / 431 (3.48%)	16 / 432 (3.70%)	18 / 433 (4.16%)	5 / 226 (2.21%)	16 / 227 (7.05%)	8 / 229 (3.49%)	0 / 16 (0.00%)	20 / 391 (5.12%)	6 / 78 (7.69%)	2 / 62 (3.23%)	6 / 348 (1.72%)	0 / 26 (0.00%)	30 / 1054 (2.85%)	30 / 1075 (2.79%)	0 / 18 (0.00%)	0 / 285 (0.00%)	1 / 700 (0.14%)	0 / 25 (0.00%)
occurrences all number	18	21	19	7	19	11	0	26	9	2	11	0	39	39	0	0	1	0
General disorders and administration site conditions
injection site erythema
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	0 / 431 (0.00%)	18 / 432 (4.17%)	28 / 433 (6.47%)	0 / 226 (0.00%)	3 / 227 (1.32%)	5 / 229 (2.18%)	0 / 16 (0.00%)	13 / 391 (3.32%)	3 / 78 (3.85%)	0 / 62 (0.00%)	2 / 348 (0.57%)	0 / 26 (0.00%)	3 / 1054 (0.28%)	3 / 1075 (0.28%)	0 / 18 (0.00%)	0 / 285 (0.00%)	0 / 700 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	24	40	0	3	8	0	15	6	0	9	0	6	6	0	0	0	0
injection site reaction
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	5 / 431 (1.16%)	27 / 432 (6.25%)	42 / 433 (9.70%)	2 / 226 (0.88%)	7 / 227 (3.08%)	12 / 229 (5.24%)	0 / 16 (0.00%)	36 / 391 (9.21%)	7 / 78 (8.97%)	2 / 62 (3.23%)	13 / 348 (3.74%)	0 / 26 (0.00%)	27 / 1054 (2.56%)	27 / 1075 (2.51%)	0 / 18 (0.00%)	0 / 285 (0.00%)	0 / 700 (0.00%)	0 / 25 (0.00%)
occurrences all number	5	47	77	2	10	47	0	94	27	10	37	0	302	302	0	0	0	0
Gastrointestinal disorders
diarrhoea
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	4 / 431 (0.93%)	10 / 432 (2.31%)	9 / 433 (2.08%)	8 / 226 (3.54%)	4 / 227 (1.76%)	8 / 229 (3.49%)	0 / 16 (0.00%)	22 / 391 (5.63%)	1 / 78 (1.28%)	2 / 62 (3.23%)	8 / 348 (2.30%)	1 / 26 (3.85%)	21 / 1054 (1.99%)	21 / 1075 (1.95%)	0 / 18 (0.00%)	1 / 285 (0.35%)	2 / 700 (0.29%)	0 / 25 (0.00%)
occurrences all number	5	11	11	8	4	8	0	29	1	2	9	1	24	24	0	1	2	0
pancreatitis
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	0 / 431 (0.00%)	0 / 432 (0.00%)	0 / 433 (0.00%)	0 / 226 (0.00%)	0 / 227 (0.00%)	1 / 229 (0.44%)	1 / 16 (6.25%)	0 / 391 (0.00%)	0 / 78 (0.00%)	0 / 62 (0.00%)	0 / 348 (0.00%)	0 / 26 (0.00%)	0 / 1054 (0.00%)	0 / 1075 (0.00%)	0 / 18 (0.00%)	0 / 285 (0.00%)	0 / 700 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
cough
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	6 / 431 (1.39%)	4 / 432 (0.93%)	7 / 433 (1.62%)	2 / 226 (0.88%)	3 / 227 (1.32%)	3 / 229 (1.31%)	0 / 16 (0.00%)	12 / 391 (3.07%)	5 / 78 (6.41%)	1 / 62 (1.61%)	2 / 348 (0.57%)	0 / 26 (0.00%)	30 / 1054 (2.85%)	30 / 1075 (2.79%)	0 / 18 (0.00%)	0 / 285 (0.00%)	1 / 700 (0.14%)	0 / 25 (0.00%)
occurrences all number	6	4	7	2	4	3	0	12	6	1	2	0	33	33	0	0	1	0
sinus congestion
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	2 / 431 (0.46%)	2 / 432 (0.46%)	2 / 433 (0.46%)	2 / 226 (0.88%)	1 / 227 (0.44%)	5 / 229 (2.18%)	1 / 16 (6.25%)	2 / 391 (0.51%)	0 / 78 (0.00%)	0 / 62 (0.00%)	0 / 348 (0.00%)	1 / 26 (3.85%)	6 / 1054 (0.57%)	6 / 1075 (0.56%)	0 / 18 (0.00%)	0 / 285 (0.00%)	0 / 700 (0.00%)	0 / 25 (0.00%)
occurrences all number	2	2	2	2	1	5	1	2	0	0	0	1	10	10	0	0	0	0
Skin and subcutaneous tissue disorders
nail psoriasis
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	7 / 431 (1.62%)	4 / 432 (0.93%)	3 / 433 (0.69%)	3 / 226 (1.33%)	2 / 227 (0.88%)	0 / 229 (0.00%)	0 / 16 (0.00%)	1 / 391 (0.26%)	2 / 78 (2.56%)	0 / 62 (0.00%)	4 / 348 (1.15%)	0 / 26 (0.00%)	3 / 1054 (0.28%)	3 / 1075 (0.28%)	1 / 18 (5.56%)	0 / 285 (0.00%)	0 / 700 (0.00%)	0 / 25 (0.00%)
occurrences all number	7	4	3	4	4	0	0	1	3	0	5	0	3	3	1	0	0	0
pruritus
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	12 / 431 (2.78%)	10 / 432 (2.31%)	6 / 433 (1.39%)	3 / 226 (1.33%)	4 / 227 (1.76%)	6 / 229 (2.62%)	1 / 16 (6.25%)	9 / 391 (2.30%)	1 / 78 (1.28%)	2 / 62 (3.23%)	4 / 348 (1.15%)	0 / 26 (0.00%)	12 / 1054 (1.14%)	12 / 1075 (1.12%)	0 / 18 (0.00%)	0 / 285 (0.00%)	0 / 700 (0.00%)	0 / 25 (0.00%)
occurrences all number	12	10	6	4	4	6	1	9	1	3	4	0	13	13	0	0	0	0
pruritus generalised
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	2 / 431 (0.46%)	4 / 432 (0.93%)	4 / 433 (0.92%)	0 / 226 (0.00%)	0 / 227 (0.00%)	2 / 229 (0.87%)	1 / 16 (6.25%)	1 / 391 (0.26%)	0 / 78 (0.00%)	0 / 62 (0.00%)	1 / 348 (0.29%)	0 / 26 (0.00%)	0 / 1054 (0.00%)	0 / 1075 (0.00%)	0 / 18 (0.00%)	1 / 285 (0.35%)	0 / 700 (0.00%)	0 / 25 (0.00%)
occurrences all number	2	4	4	0	0	2	1	1	0	0	1	0	0	0	0	1	0	0
psoriasis
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	16 / 431 (3.71%)	2 / 432 (0.46%)	4 / 433 (0.92%)	5 / 226 (2.21%)	6 / 227 (2.64%)	2 / 229 (0.87%)	1 / 16 (6.25%)	4 / 391 (1.02%)	2 / 78 (2.56%)	1 / 62 (1.61%)	4 / 348 (1.15%)	0 / 26 (0.00%)	21 / 1054 (1.99%)	21 / 1075 (1.95%)	0 / 18 (0.00%)	5 / 285 (1.75%)	11 / 700 (1.57%)	2 / 25 (8.00%)
occurrences all number	16	2	4	5	6	2	2	4	2	5	4	0	23	23	0	5	11	2
urticaria
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	0 / 431 (0.00%)	1 / 432 (0.23%)	4 / 433 (0.92%)	0 / 226 (0.00%)	0 / 227 (0.00%)	4 / 229 (1.75%)	1 / 16 (6.25%)	2 / 391 (0.51%)	0 / 78 (0.00%)	0 / 62 (0.00%)	0 / 348 (0.00%)	0 / 26 (0.00%)	7 / 1054 (0.66%)	7 / 1075 (0.65%)	0 / 18 (0.00%)	0 / 285 (0.00%)	0 / 700 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	1	4	0	0	4	1	2	0	0	0	0	8	8	0	0	0	0
Psychiatric disorders
insomnia
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	0 / 431 (0.00%)	1 / 432 (0.23%)	3 / 433 (0.69%)	0 / 226 (0.00%)	1 / 227 (0.44%)	0 / 229 (0.00%)	0 / 16 (0.00%)	0 / 391 (0.00%)	0 / 78 (0.00%)	0 / 62 (0.00%)	3 / 348 (0.86%)	0 / 26 (0.00%)	11 / 1054 (1.04%)	11 / 1075 (1.02%)	1 / 18 (5.56%)	0 / 285 (0.00%)	0 / 700 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	1	3	0	1	0	0	0	0	0	3	0	11	11	1	0	0	0
Musculoskeletal and connective tissue disorders
arthralgia
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	9 / 431 (2.09%)	4 / 432 (0.93%)	9 / 433 (2.08%)	6 / 226 (2.65%)	13 / 227 (5.73%)	13 / 229 (5.68%)	0 / 16 (0.00%)	14 / 391 (3.58%)	8 / 78 (10.26%)	3 / 62 (4.84%)	4 / 348 (1.15%)	1 / 26 (3.85%)	54 / 1054 (5.12%)	54 / 1075 (5.02%)	0 / 18 (0.00%)	1 / 285 (0.35%)	3 / 700 (0.43%)	0 / 25 (0.00%)
occurrences all number	11	4	12	6	15	16	0	16	10	3	4	1	70	70	0	1	4	0
back pain
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	4 / 431 (0.93%)	6 / 432 (1.39%)	4 / 433 (0.92%)	7 / 226 (3.10%)	13 / 227 (5.73%)	6 / 229 (2.62%)	0 / 16 (0.00%)	16 / 391 (4.09%)	1 / 78 (1.28%)	6 / 62 (9.68%)	6 / 348 (1.72%)	0 / 26 (0.00%)	45 / 1054 (4.27%)	45 / 1075 (4.19%)	1 / 18 (5.56%)	0 / 285 (0.00%)	1 / 700 (0.14%)	0 / 25 (0.00%)
occurrences all number	4	6	6	8	15	6	0	16	1	6	6	0	50	50	1	0	1	0
musculoskeletal pain
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	0 / 431 (0.00%)	1 / 432 (0.23%)	2 / 433 (0.46%)	3 / 226 (1.33%)	1 / 227 (0.44%)	3 / 229 (1.31%)	0 / 16 (0.00%)	7 / 391 (1.79%)	4 / 78 (5.13%)	0 / 62 (0.00%)	1 / 348 (0.29%)	0 / 26 (0.00%)	17 / 1054 (1.61%)	17 / 1075 (1.58%)	0 / 18 (0.00%)	0 / 285 (0.00%)	0 / 700 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	1	2	3	1	4	0	11	4	0	1	0	18	18	0	0	0	0
plantar fasciitis
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	0 / 431 (0.00%)	0 / 432 (0.00%)	0 / 433 (0.00%)	1 / 226 (0.44%)	0 / 227 (0.00%)	0 / 229 (0.00%)	1 / 16 (6.25%)	0 / 391 (0.00%)	0 / 78 (0.00%)	0 / 62 (0.00%)	0 / 348 (0.00%)	0 / 26 (0.00%)	5 / 1054 (0.47%)	5 / 1075 (0.47%)	0 / 18 (0.00%)	0 / 285 (0.00%)	0 / 700 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	0	0	1	0	0	1	0	0	0	0	0	5	5	0	0	0	0
Infections and infestations
cellulitis
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	0 / 431 (0.00%)	1 / 432 (0.23%)	0 / 433 (0.00%)	0 / 226 (0.00%)	1 / 227 (0.44%)	2 / 229 (0.87%)	0 / 16 (0.00%)	4 / 391 (1.02%)	5 / 78 (6.41%)	0 / 62 (0.00%)	3 / 348 (0.86%)	0 / 26 (0.00%)	14 / 1054 (1.33%)	14 / 1075 (1.30%)	0 / 18 (0.00%)	1 / 285 (0.35%)	0 / 700 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	1	0	0	1	2	0	4	8	0	3	0	14	14	0	1	0	0
cystitis
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	1 / 431 (0.23%)	2 / 432 (0.46%)	1 / 433 (0.23%)	1 / 226 (0.44%)	6 / 227 (2.64%)	1 / 229 (0.44%)	0 / 16 (0.00%)	3 / 391 (0.77%)	4 / 78 (5.13%)	2 / 62 (3.23%)	4 / 348 (1.15%)	0 / 26 (0.00%)	17 / 1054 (1.61%)	17 / 1075 (1.58%)	0 / 18 (0.00%)	0 / 285 (0.00%)	1 / 700 (0.14%)	0 / 25 (0.00%)
occurrences all number	1	2	1	1	8	1	0	3	5	3	4	0	22	22	0	0	1	0
eye infection
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	1 / 431 (0.23%)	0 / 432 (0.00%)	0 / 433 (0.00%)	0 / 226 (0.00%)	0 / 227 (0.00%)	0 / 229 (0.00%)	1 / 16 (6.25%)	2 / 391 (0.51%)	0 / 78 (0.00%)	1 / 62 (1.61%)	0 / 348 (0.00%)	0 / 26 (0.00%)	1 / 1054 (0.09%)	1 / 1075 (0.09%)	0 / 18 (0.00%)	1 / 285 (0.35%)	0 / 700 (0.00%)	0 / 25 (0.00%)
occurrences all number	1	0	0	0	0	0	1	2	0	1	0	0	1	1	0	1	0	0
influenza
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	0 / 431 (0.00%)	4 / 432 (0.93%)	2 / 433 (0.46%)	4 / 226 (1.77%)	8 / 227 (3.52%)	7 / 229 (3.06%)	0 / 16 (0.00%)	7 / 391 (1.79%)	2 / 78 (2.56%)	2 / 62 (3.23%)	3 / 348 (0.86%)	2 / 26 (7.69%)	28 / 1054 (2.66%)	28 / 1075 (2.60%)	0 / 18 (0.00%)	2 / 285 (0.70%)	3 / 700 (0.43%)	0 / 25 (0.00%)
occurrences all number	0	4	2	5	8	7	0	7	2	2	4	2	31	31	0	2	3	0
nasopharyngitis
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	41 / 431 (9.51%)	45 / 432 (10.42%)	49 / 433 (11.32%)	26 / 226 (11.50%)	41 / 227 (18.06%)	51 / 229 (22.27%)	0 / 16 (0.00%)	77 / 391 (19.69%)	19 / 78 (24.36%)	11 / 62 (17.74%)	37 / 348 (10.63%)	4 / 26 (15.38%)	178 / 1054 (16.89%)	178 / 1075 (16.56%)	0 / 18 (0.00%)	1 / 285 (0.35%)	9 / 700 (1.29%)	0 / 25 (0.00%)
occurrences all number	45	46	57	32	65	71	0	116	25	16	45	7	314	314	0	1	9	0
pharyngitis
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	6 / 431 (1.39%)	3 / 432 (0.69%)	2 / 433 (0.46%)	5 / 226 (2.21%)	8 / 227 (3.52%)	1 / 229 (0.44%)	1 / 16 (6.25%)	13 / 391 (3.32%)	1 / 78 (1.28%)	1 / 62 (1.61%)	6 / 348 (1.72%)	0 / 26 (0.00%)	33 / 1054 (3.13%)	33 / 1075 (3.07%)	0 / 18 (0.00%)	0 / 285 (0.00%)	1 / 700 (0.14%)	0 / 25 (0.00%)
occurrences all number	6	3	2	5	10	1	1	15	1	1	6	0	44	44	0	0	1	0
sinusitis
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	4 / 431 (0.93%)	6 / 432 (1.39%)	5 / 433 (1.15%)	7 / 226 (3.10%)	11 / 227 (4.85%)	8 / 229 (3.49%)	1 / 16 (6.25%)	18 / 391 (4.60%)	3 / 78 (3.85%)	2 / 62 (3.23%)	11 / 348 (3.16%)	0 / 26 (0.00%)	46 / 1054 (4.36%)	46 / 1075 (4.28%)	0 / 18 (0.00%)	2 / 285 (0.70%)	1 / 700 (0.14%)	0 / 25 (0.00%)
occurrences all number	4	6	5	8	13	8	1	20	3	3	11	0	56	56	0	3	1	0
staphylococcal infection
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	1 / 431 (0.23%)	0 / 432 (0.00%)	1 / 433 (0.23%)	1 / 226 (0.44%)	1 / 227 (0.44%)	1 / 229 (0.44%)	0 / 16 (0.00%)	0 / 391 (0.00%)	1 / 78 (1.28%)	0 / 62 (0.00%)	1 / 348 (0.29%)	0 / 26 (0.00%)	5 / 1054 (0.47%)	5 / 1075 (0.47%)	1 / 18 (5.56%)	0 / 285 (0.00%)	0 / 700 (0.00%)	0 / 25 (0.00%)
occurrences all number	1	0	1	1	1	1	0	0	1	0	1	0	5	5	1	0	0	0
upper respiratory tract infection
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	16 / 431 (3.71%)	20 / 432 (4.63%)	24 / 433 (5.54%)	18 / 226 (7.96%)	20 / 227 (8.81%)	18 / 229 (7.86%)	2 / 16 (12.50%)	53 / 391 (13.55%)	8 / 78 (10.26%)	4 / 62 (6.45%)	18 / 348 (5.17%)	2 / 26 (7.69%)	89 / 1054 (8.44%)	89 / 1075 (8.28%)	0 / 18 (0.00%)	0 / 285 (0.00%)	1 / 700 (0.14%)	0 / 25 (0.00%)
occurrences all number	17	20	27	26	22	21	4	76	12	4	21	4	129	129	0	0	1	0
urinary tract infection
alternative dictionary used: MedDRA 21.1
subjects affected / exposed	8 / 431 (1.86%)	6 / 432 (1.39%)	2 / 433 (0.46%)	3 / 226 (1.33%)	2 / 227 (0.88%)	10 / 229 (4.37%)	0 / 16 (0.00%)	11 / 391 (2.81%)	4 / 78 (5.13%)	2 / 62 (3.23%)	11 / 348 (3.16%)	0 / 26 (0.00%)	31 / 1054 (2.94%)	31 / 1075 (2.88%)	0 / 18 (0.00%)	0 / 285 (0.00%)	2 / 700 (0.29%)	0 / 25 (0.00%)
occurrences all number	8	6	2	3	2	10	0	13	5	4	13	0	48	48	0	0	2	0

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Were there any global substantial amendments to the protocol? Yes

28 Mar 2017

The overall changes were to add 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. Thus, 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

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Participants with static Physician Global Assessment (sPGA) of 0 or 1 (Efficacy of Ixekizumab in participants with moderate to severe plaque Ps Measure: sPGA)

Primary: Percentage of Participants with static Physician Global Assessment (sPGA) of 0 or 1 (Efficacy of Ixekizumab in participants with moderate to severe plaque Ps Measure: sPGA)

Primary: Percentage of Participants achieving ≥75% Improvement in Ps Area and Severity Index (PASI75) (Efficacy of Ixekizumab in participants with moderate to severe plaque psoriasis Measure: PASI)

Primary: Percentage of Participants achieving ≥75% Improvement in Ps Area and Severity Index (PASI75) (Efficacy of Ixekizumab in participants with moderate to severe plaque psoriasis Measure: PASI)

Secondary: Percentage of Participants Achieving an sPGA of 0 (Efficacy of Ixekizumab in participants with moderate to severe plaque Ps Measure: sPGA)

Secondary: Percentage of Participants Achieving an sPGA of 0 (Efficacy of Ixekizumab in participants with moderate to severe plaque Ps Measure: sPGA)

Secondary: Percentage of Participants Achieving PASI 90% (PASI90) or 100% (PASI100) (Efficacy of Ixekizumab in participants with moderate to severe plaque Ps Measure: PASI)

Secondary: Percentage of Participants Achieving PASI 90% (PASI90) or 100% (PASI100) (Efficacy of Ixekizumab in participants with moderate to severe plaque Ps Measure: PASI)

Secondary: Percentage of participants maintaining sPGA 0 or 1 after Re-Randomization at start of maintenance dosing period

Secondary: Percentage of participants maintaining sPGA 0 or 1 after Re-Randomization at start of maintenance dosing period

Secondary: Percentage of Participants with Itch Numeric Rating Scale (Itch NRS) Score ≥4 Point reduction from baseline

Secondary: Percentage of Participants with Itch Numeric Rating Scale (Itch NRS) Score ≥4 Point reduction from baseline

Secondary: Change from baseline in Dermatology-Specific Quality of Life Index (DLQI) Score

Secondary: Change from baseline in Dermatology-Specific Quality of Life Index (DLQI) Score

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

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

Secondary: Percent of Body Surface Area (BSA) involvement of Ps

Secondary: Percent of Body Surface Area (BSA) involvement of Ps

Secondary: Change from baseline in Psoriasis Scalp Severity Index (PSSI)

Secondary: Change from baseline in Psoriasis Scalp Severity Index (PSSI)

Secondary: Change from Baseline in all scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) (Quality of life and outcome assessments. Measures: Participant Reported Outcomes [PRO])

Secondary: Change from Baseline in all scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) (Quality of life and outcome assessments. Measures: Participant Reported Outcomes [PRO])

Secondary: Change from Baseline in Quick Inventory of Depressive Symptomatology-Self Reported 16 Items (QIDS-SR16)

Secondary: Change from Baseline in Quick Inventory of Depressive Symptomatology-Self Reported 16 Items (QIDS-SR16)

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 of Disease Severity (PatGA)

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

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

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

Secondary: Pharmacokinetics (PK): Trough concentration at steady state (Ctrough ss)

Secondary: Pharmacokinetics (PK): Trough concentration at steady state (Ctrough ss)

Secondary: Percentage of Participants with Anti-ixekizumab antibodies

Secondary: Percentage of Participants with Anti-ixekizumab antibodies

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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