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Clinical Trial Results:
A 12-Week Multicenter, Randomized, Double-Blind, Placebo Controlled Study Comparing the Efficacy and Safety of LY2439821 to Etanercept and Placebo in Patients with Moderate to Severe Plaque Psoriasis with a Long-Term Extension Period

Summary
EudraCT number	2011-004368-31
Trial protocol	HU DE BG PL
Global end of trial date	22 Jul 2019

Results information
Results version number	v1(current)
This version publication date	02 Aug 2020
First version publication date	02 Aug 2020
Other versions

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

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Trial information

Top of page

Sponsor protocol code

I1F-MC-RHBC

ISRCTN number

US NCT number

NCT01646177

WHO universal trial number (UTN)

Other trial identifiers

Trial Number: 13685

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

22 Jul 2019

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

22 Jul 2019

Was the trial ended prematurely?

Main objective of the trial

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

Protection of trial subjects

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

Background therapy

Evidence for comparator

Actual start date of recruitment

28 Jul 2012

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 21

Country: Number of subjects enrolled

Chile: 76

Country: Number of subjects enrolled

Mexico: 5

Country: Number of subjects enrolled

Bulgaria: 48

Country: Number of subjects enrolled

Germany: 312

Country: Number of subjects enrolled

Hungary: 113

Country: Number of subjects enrolled

Poland: 39

Country: Number of subjects enrolled

Russian Federation: 77

Country: Number of subjects enrolled

Canada: 152

Country: Number of subjects enrolled

United States: 503

Worldwide total number of subjects

1346

EEA total number of subjects

512

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)

1238

From 65 to 84 years

107

85 years and over

Subject disposition

Top of page

Recruitment details

No Text Available

Screening details

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

Period 1 title

Blinded Induction Dosing (Week 0-12)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

Placebo

Arm description

Placebo (PBO) for ixekizumab (Week 0) given as 2 subcutaneous (SC) injections followed by placebo for ixekizumab Q2W (Weeks 2, 4, 6, 8, and 10). Placebo for etanercept (1 SC injection) given twice weekly (every 3-4 days) starting at Week 0 up to Week 12.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Administered SC

50 mg Etanercept (ETN)

Arm description

Etanercept 50 mg (1 SC injection) given twice weekly (every 3-4 days) starting at Week 0 and up to Week 12. Placebo for ixekizumab given as 2 SC injections (Week 0) followed by placebo for ixekizumab Q2W given as 1 SC injection (Weeks 2, 4, 6, 8, and 10).

Arm type

Active comparator

Investigational medicinal product name

Etanercept

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Etanercept 50 mg (1 SC injection) given twice weekly (every 3-4 days) starting at Week 0 and up to Week 12

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Placebo for ixekizumab given as 2 SC injections (Week 0) followed by placebo for ixekizumab Q2W given as 1 SC injection (Weeks 2, 4, 6, 8, and 10).

80 mg ixekizumab Dosing Regimen 2 (Q4W)

Arm description

A starting dose of 160 mg (Week 0) given as 2 SC injections followed by 80 mg given as 1 SC injection Q4W (Weeks 4 and 8). Placebo for ixekizumab given as 1 SC injection at Weeks 2, 6, and 10. Placebo for etanercept (1 SC injection) given twice weekly starting at Week 0 up to Week 12.

Arm type

Experimental

Investigational medicinal product name

Ixekizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

A starting dose of 160 mg (Week 0) given as 2 SC injections followed by 80 mg given as 1 SC injection Q4W (Weeks 4 and 8).

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Subcutaneous use

Dosage and administration details

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

80 mg ixekizumab Dosing Regimen 1 (Q2W)

Arm description

A starting dose of 160 mg (Week 0) given as 2 SC injections followed by 80 mg given as 1 SC injection Q2W (Weeks 2, 4, 6, 8, and 10). Placebo for etanercept (1 SC injection) given twice weekly starting at Week 0 up to Week 12.

Arm type

Experimental

Investigational medicinal product name

Ixekizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

A starting dose of 160 mg (Week 0) given as 2 SC injections followed by 80 mg given as 1 SC injection Q2W (Weeks 2, 4, 6, 8, and 10).

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Placebo for etanercept (1 SC injection) given twice weekly starting at Week 0 up to Week 12.

Number of subjects in period 1	Placebo	50 mg Etanercept (ETN)	80 mg ixekizumab Dosing Regimen 2 (Q4W)	80 mg ixekizumab Dosing Regimen 1 (Q2W)
Started	193	382	386	385
Received at least one dose of study drug	193	382	382	384
Completed	183	369	360	363
Not completed	10	13	26	22
Consent withdrawn by subject	3	2	4	4
Physician decision	1	2	1	2
Adverse event, non-fatal	2	4	9	8
Lost to follow-up	3	2	2	-
Protocol deviation	1	3	8	7
Lack of efficacy	-	-	2	1

Period 2 title

Long-Term Extension Period (Week 12-264)

Is this the baseline period?

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

PBO/IXE80Q4W

Arm description

Participants who received placebo during the induction period and received 80 mg ixekizumab SC injection every four weeks (IXE80Q4W) in the Long-term extension 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 received a starting dose of 160 mg of ixekizumab as 2 SC injections at Week 12 and 80 mg ixekizumab as 1 SC injection Q4W thereafter.

ETN/IXE80Q4W

Arm description

Participants who received Etanercept during the induction period and received IXE80Q4W in the long-term extension 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 received placebo as 2 SC injections at Week 12 and 80 mg ixekizumab as 1 SC injection Q4W thereafter.

IXE80Q4W/IXE80Q4W

Arm description

Participants who received 80 mg ixe Q4W during the induction period and received IXE80Q4W in the long-term extension 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 received 80 mg ixekizumab as 1 SC injection + a placebo injection at Week 12 and 80 mg ixekizumab as 1 SC injection Q4W thereafter.

IXE80Q2W/IXE80Q4W

Arm description

Participants who received 80 mg ixe Q2W (IXE80Q2W) during the induction period and received IXE80Q4W in the long-term extension 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 received 80 mg ixekizumab as 1 SC injection + a placebo injection at Week 12 and 80 mg ixekizumab as 1 SC injection Q4W thereafter.

Number of subjects in period 2	PBO/IXE80Q4W	ETN/IXE80Q4W	IXE80Q4W/IXE80Q4W	IXE80Q2W/IXE80Q4W
Started	183	369	360	362
Received at least one dose of study drug	183	369	360	362
Completed	135	256	244	255
Not completed	48	113	116	107
Adverse event, serious fatal	1	3	1	3
Parent/Caregiver Decision	-	-	-	1
Consent withdrawn by subject	11	30	29	27
Physician decision	3	5	5	5
Clinical Relapse	1	1	1	4
Adverse event, non-fatal	16	34	43	30
Sponsor Decision	3	2	2	2
Lost to follow-up	6	17	23	18
Missing Disposition Form	-	3	2	1
Lack of efficacy	6	14	10	11
Protocol deviation	1	4	-	5

Period 3 title

Follow-Up Period (Minimum of 12 Weeks)

Is this the baseline period?

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

PBO Follow-Up Period

Arm description

Participants who received PBO in the Induction Period and entered the Post-Treatment Follow-up Period.

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 in the Induction Period and entered the Post-Treatment Follow-up Period.

ETN Follow-Up Period

Arm description

Participants who received etanercept (ETN) in the Induction Period and entered the Post-Treatment Follow-up Period.

Arm type

Active comparator

Investigational medicinal product name

Etanercept

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants who received etanercept (ETN) in the Induction Period and entered the Post-Treatment Follow-up Period.

IXE80Q4W Follow-Up Period

Arm description

Participants who received 80 mg ixe Q4W in the Induction Period and entered the Post-Treatment Follow-up 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 Q4W in the Induction Period and entered the Post-Treatment Follow-up Period.

IXE80Q2W Follow-Up Period

Arm description

Participants who received 80 mg ixe Q2W in the Induction Period and entered the Post-Treatment Follow-up 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 Q2W in the Induction Period and entered the Post-Treatment Follow-up Period.

Number of subjects in period 3	PBO Follow-Up Period	ETN Follow-Up Period	IXE80Q4W Follow-Up Period	IXE80Q2W Follow-Up Period
Started	157	309	305	313
Received at least one dose of study drug	157	309	305	313
Completed	126	233	225	230
Not completed	31	76	80	83
Adverse event, serious fatal	1	-	1	1
Consent withdrawn by subject	7	21	19	19
Physician decision	1	2	2	3
Clinical Relapse	-	1	1	3
Adverse event, non-fatal	13	28	34	30
Sponsor Decision	-	1	1	1
Lost to follow-up	4	8	9	9
Entry Criteria Not Met	-	-	1	1
Lack of efficacy	4	9	8	9
Protocol deviation	1	6	4	7

Baseline characteristics

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Reporting group title

Placebo

Reporting group description

Reporting group title

50 mg Etanercept (ETN)

Reporting group description

Reporting group title

80 mg ixekizumab Dosing Regimen 2 (Q4W)

Reporting group description

Reporting group title

80 mg ixekizumab Dosing Regimen 1 (Q2W)

Reporting group description

Reporting group values	Placebo	50 mg Etanercept (ETN)	80 mg ixekizumab Dosing Regimen 2 (Q4W)	80 mg ixekizumab Dosing Regimen 1 (Q2W)	Total
Number of subjects	193	382	386	385	1346
Age categorical
Units: Subjects
<=18 years	0	0	0	0	0
Between 18 and 65 years	180	349	358	351	1238
>=65 years	13	33	28	34	108
Gender categorical
Units: Subjects
Female	56	113	128	131	428
Male	137	269	258	254	918
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	25	52	50	57	184
Not Hispanic or Latino	133	263	269	259	924
Unknown or Not Reported	35	67	67	69	238
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	1	4	4	1	10
Asian	7	11	11	12	41
Native Hawaiian or Other Pacific Islander	0	1	1	4	6
Black or African American	8	10	9	5	32
White	176	351	360	361	1248
More than one race	1	5	1	2	9
Unknown or Not Reported	0	0	0	0	0
Region of Enrollment
Units: Subjects
Argentina	2	7	6	6	21
Chile	11	21	22	22	76
Mexico	1	2	1	1	5
Bulgaria	9	12	14	13	48
Germany	45	87	90	90	312
Hungary	18	31	31	33	113
Poland	5	10	11	13	39
Russia	11	22	20	24	77
Canada	22	44	44	42	152
United States	69	146	147	141	503

End points

Top of page

Reporting group title

Placebo

Reporting group description

Reporting group title

50 mg Etanercept (ETN)

Reporting group description

Reporting group title

80 mg ixekizumab Dosing Regimen 2 (Q4W)

Reporting group description

Reporting group title

80 mg ixekizumab Dosing Regimen 1 (Q2W)

Reporting group description

Reporting group title

PBO/IXE80Q4W

Reporting group description

Participants who received placebo during the induction period and received 80 mg ixekizumab SC injection every four weeks (IXE80Q4W) in the Long-term extension period.

Reporting group title

ETN/IXE80Q4W

Reporting group description

Participants who received Etanercept during the induction period and received IXE80Q4W in the long-term extension period.

Reporting group title

IXE80Q4W/IXE80Q4W

Reporting group description

Participants who received 80 mg ixe Q4W during the induction period and received IXE80Q4W in the long-term extension period.

Reporting group title

IXE80Q2W/IXE80Q4W

Reporting group description

Participants who received 80 mg ixe Q2W (IXE80Q2W) during the induction period and received IXE80Q4W in the long-term extension period.

Reporting group title

PBO Follow-Up Period

Reporting group description

Participants who received PBO in the Induction Period and entered the Post-Treatment Follow-up Period.

Reporting group title

ETN Follow-Up Period

Reporting group description

Participants who received etanercept (ETN) in the Induction Period and entered the Post-Treatment Follow-up Period.

Reporting group title

IXE80Q4W Follow-Up Period

Reporting group description

Participants who received 80 mg ixe Q4W in the Induction Period and entered the Post-Treatment Follow-up Period.

Reporting group title

IXE80Q2W Follow-Up Period

Reporting group description

Participants who received 80 mg ixe Q2W in the Induction Period and entered the Post-Treatment Follow-up Period.

Primary: Number of participants achieving a static Physician Global Assessment (sPGA) of (0, 1) (Efficacy of ixekizumab in participants with moderate to severe chronic plaque psoriasis. Measure: sPGA)

Top of page

End point title

Number of participants achieving a static Physician Global Assessment (sPGA) of (0, 1) (Efficacy of ixekizumab in participants with moderate to severe chronic plaque psoriasis. Measure: sPGA)

End point description

The sPGA is a physician’s determination of the participant’s psoriasis lesions overall at a given time point categorized by descriptions for induration, erythema, and scaling. For the analysis of responses, the participant’s psoriasis is assessed as clear (0), minimal (1), mild (2), moderate (3), severe (4), or very severe (5). An sPGA (0,1) response was defined as a post-baseline sPGA score of 0 or 1. Participants who did not meet clinical response criteria or have missing data at Week 12 will be considered non-responders for the Non-Responder Imputation (NRI) analysis.

End point type

Primary

End point timeframe

Week 12

End point values	Placebo	50 mg Etanercept (ETN)	80 mg ixekizumab Dosing Regimen 2 (Q4W)	80 mg ixekizumab Dosing Regimen 1 (Q2W)
Number of subjects analysed	193 ^[1]	382 ^[2]	386 ^[3]	385 ^[4]
Units: participants	13	159	291	310

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

sPGA Statistical Analysis 1

Comparison groups

Placebo v 50 mg Etanercept (ETN)

Number of subjects included in analysis

575

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

sPGA Statistical Analysis 2

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 2 (Q4W)

Number of subjects included in analysis

579

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

sPGA Statistical Analysis 3

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 1 (Q2W)

Number of subjects included in analysis

578

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

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

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End point title

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

End point description

The PASI combines assessments of the extent of body-surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of desquamation (scaling), erythema, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis to 72 for the most severe disease. Participants achieving PASI 75 was defined as having an improvement of at least 75% in the PASI scores compared to baseline. Participants who did not meet clinical response criteria or have missing data at Week 12 will be considered non-responders for the Non-Responder Imputation (NRI) analysis.

End point type

Primary

End point timeframe

Week 12

End point values	Placebo	50 mg Etanercept (ETN)	80 mg ixekizumab Dosing Regimen 2 (Q4W)	80 mg ixekizumab Dosing Regimen 1 (Q2W)
Number of subjects analysed	193 ^[5]	382 ^[6]	386 ^[7]	385 ^[8]
Units: participants	14	204	325	336

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

PASI 75 Statistical Analysis 1

Comparison groups

Placebo v 50 mg Etanercept (ETN)

Number of subjects included in analysis

575

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

PASI 75 Statistical Analysis 2

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 2 (Q4W)

Number of subjects included in analysis

579

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

PASI 75 Statistical Analysis 3

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 1 (Q2W)

Number of subjects included in analysis

578

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

Secondary: Number of participants achieving an sPGA (0) (Efficacy of ixekizumab in participants with moderate to severe chronic plaque psoriasis. Measure: sPGA)

Top of page

End point title

Number of participants achieving an sPGA (0) (Efficacy of ixekizumab in participants with moderate to severe chronic plaque psoriasis. Measure: sPGA)

End point description

The sPGA is a physician’s determination of the participant’s psoriasis lesions overall at a given time point categorized by descriptions for induration, erythema, and scaling. For the analysis of responses, the participant’s psoriasis is assessed as clear (0), minimal (1), mild (2), moderate (3), severe (4), or very severe (5). An sPGA (0) response was defined as a post-baseline sPGA score of 0. Participants who did not meet clinical response criteria or have missing data at Week 12 will be considered non-responders for the Non-Responder Imputation (NRI) analysis.

End point type

Secondary

End point timeframe

Week 12

End point values	Placebo	50 mg Etanercept (ETN)	80 mg ixekizumab Dosing Regimen 2 (Q4W)	80 mg ixekizumab Dosing Regimen 1 (Q2W)
Number of subjects analysed	193 ^[9]	382 ^[10]	386 ^[11]	385 ^[12]
Units: participants	0	33	139	155

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

sPGA (0) Statistical Analysis 1

Comparison groups

50 mg Etanercept (ETN) v Placebo

Number of subjects included in analysis

575

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

sPGA (0) Statistical Analysis 2

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 2 (Q4W)

Number of subjects included in analysis

579

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

sPGA (0) Statistical Analysis 3

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 1 (Q2W)

Number of subjects included in analysis

578

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

Secondary: Number of Participants Achieving ≥90% (PASI 90) Improvement (Efficacy of ixekizumab in participants with moderate to severe chronic plaque psoriasis. Measure: PASI)

Top of page

End point title

Number of Participants Achieving ≥90% (PASI 90) Improvement (Efficacy of ixekizumab in participants with moderate to severe chronic plaque psoriasis. Measure: PASI)

End point description

The PASI combines assessments of the extent of body-surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of desquamation (scaling), erythema, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis to 72 for the most severe disease. Participants achieving PASI 90 were defined as having an improvement of at least 90% in the PASI scores compared to baseline. Participants who did not meet clinical response criteria or have missing data at Week 12 will be considered non-responders for the Non-Responder Imputation (NRI) analysis.

End point type

Secondary

End point timeframe

Week 12

End point values	Placebo	50 mg Etanercept (ETN)	80 mg ixekizumab Dosing Regimen 2 (Q4W)	80 mg ixekizumab Dosing Regimen 1 (Q2W)
Number of subjects analysed	193 ^[13]	382 ^[14]	386 ^[15]	385 ^[16]
Units: participants	6	98	252	262

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

PASI 90 Statisitical Analysis 1

Comparison groups

Placebo v 50 mg Etanercept (ETN)

Number of subjects included in analysis

575

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

PASI 90 Statistical Analysis 2

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 2 (Q4W)

Number of subjects included in analysis

579

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

PASI 90 Statistical Analysis 3

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 1 (Q2W)

Number of subjects included in analysis

578

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

Secondary: Number of Participants Achieving 100% (PASI 100) Improvement (Efficacy of ixekizumab in participants with moderate to severe chronic plaque psoriasis. Measure: PASI)

Top of page

End point title

Number of Participants Achieving 100% (PASI 100) Improvement (Efficacy of ixekizumab in participants with moderate to severe chronic plaque psoriasis. Measure: PASI)

End point description

The PASI combines assessments of the extent of body-surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of desquamation (scaling), erythema, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis to 72 for the most severe disease. Participants achieving PASI 100 were defined as having an improvement of at least 100% in the PASI scores compared to baseline. Participants who did not meet clinical response criteria or have missing data at Week 12 will be considered non-responders for the Non-Responder Imputation (NRI) analysis.

End point type

Secondary

End point timeframe

Week 12

End point values	Placebo	50 mg Etanercept (ETN)	80 mg ixekizumab Dosing Regimen 2 (Q4W)	80 mg ixekizumab Dosing Regimen 1 (Q2W)
Number of subjects analysed	193 ^[17]	382 ^[18]	386 ^[19]	385 ^[20]
Units: participants	0	28	135	145

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

PASI 100 Statistical Analysis 1

Comparison groups

Placebo v 50 mg Etanercept (ETN)

Number of subjects included in analysis

575

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

PASI 100 Statistical Analysis 2

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 2 (Q4W)

Number of subjects included in analysis

579

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

PASI 100 Statistical Analysis 3

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 1 (Q2W)

Number of subjects included in analysis

578

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

Secondary: Number of Participants Achieving an Itch Numeric Rating Scale (NRS) ≥4 Point Reduction [Quality of Life and Outcome Assessments. Measures: Patient Reported Outcomes (PRO)]

Top of page

End point title

Number of Participants Achieving an Itch Numeric Rating Scale (NRS) ≥4 Point Reduction [Quality of Life and Outcome Assessments. Measures: Patient Reported Outcomes (PRO)]

End point description

The Itch NRS is a participant-administered single-item 11-point horizontal scale anchored at 0 and 10, with 0 representing “no itch” and 10 representing “worst itch imaginable.” Participants indicate their overall severity of itching from Psoriasis by circling the number that best describes the worst level of itching in the past 24 hours. Participants who did not meet clinical response criteria or have missing data at Week 12 will be considered non-responders for the NRI analysis.

End point type

Secondary

End point timeframe

Week 12

End point values	Placebo	50 mg Etanercept (ETN)	80 mg ixekizumab Dosing Regimen 2 (Q4W)	80 mg ixekizumab Dosing Regimen 1 (Q2W)
Number of subjects analysed	158 ^[21]	312 ^[22]	313 ^[23]	320 ^[24]
Units: participants	33	200	250	264

Notes
[21] - All randomized participants and had an Itch NRS score >=4 at baseline.
[22] - All randomized participants and had an Itch NRS score >=4 at baseline.
[23] - All randomized participants and had an Itch NRS score >=4 at baseline.
[24] - All randomized participants and had an Itch NRS score >=4 at baseline.

Itch NRS Statistical Analysis 1

Comparison groups

Placebo v 50 mg Etanercept (ETN)

Number of subjects included in analysis

470

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

Itch NRS Statistical Analysis 2

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 2 (Q4W)

Number of subjects included in analysis

471

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

Itch NRS Statistical Analysis 3

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 1 (Q2W)

Number of subjects included in analysis

478

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

Secondary: Change from Baseline in Dermatology Life Quality Index (DLQI) Total Score

Top of page

End point title

Change from Baseline in Dermatology Life Quality Index (DLQI) Total Score

End point description

The DLQI is a simple, participant-administered, 10 question, validated, quality-of-life questionnaire that covers 6 domains: symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories include “not at all,” “a lot,” and “very much,” with corresponding scores of 1, 2, and 3, respectively, and unanswered (“not relevant”) responses scored as “0.” Totals range from 0 to 30 (less to more impairment), and a 5 point change from baseline is considered clinically relevant. Least Square (LS) Means in total DLQI score were calculated using Mixed Model Repeated Measures (MMRM) with baseline score as covariate, treatment, pooled center, visit and treatment-by-visit interaction as fixed effects.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo	50 mg Etanercept (ETN)	80 mg ixekizumab Dosing Regimen 2 (Q4W)	80 mg ixekizumab Dosing Regimen 1 (Q2W)
Number of subjects analysed	191 ^[25]	376 ^[26]	375 ^[27]	377 ^[28]
Units: Units on a Scale
least squares mean (standard error)	-1.7 ( 0.32 )	-8.0 ( 0.23 )	-9.6 ( 0.23 )	-10.2 ( 0.23 )

Notes
[25] - All randomized participants who had at least one post-dose measurement of DLQI.
[26] - All randomized participants who had at least one post-dose measurement of DLQI.
[27] - All randomized participants who had at least one post-dose measurement of DLQI.
[28] - All randomized participants who had at least one post-dose measurement of DLQI.

DLQI Statistical Analysis 1

Comparison groups

50 mg Etanercept (ETN) v Placebo

Number of subjects included in analysis

567

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Confidence interval

DLQI Statistical Analysis 2

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 2 (Q4W)

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Confidence interval

DLQI Statistical Analysis 3

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 1 (Q2W)

Number of subjects included in analysis

568

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Confidence interval

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

Top of page

End point title

Change from Baseline in Nail Psoriasis Severity Index (NAPSI) Score

End point description

The NAPSI is a numeric, reproducible, objective tool used to evaluate the severity of fingernail bed psoriasis and fingernail matrix psoriasis 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 psoriasis: 0 (none) to 4 (psoriasis in 4 quadrants of the nail) and fingernail matrix psoriasis (0 to 4) depending on the presence (score of 1) or absence (score of 0) of any of the features of fingernail bed and fingernail matrix psoriasis 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, and the sum of all the fingernails is the total NAPSI score (range, 0 to 80). LS Means in NAPSI score were calculated using MMRM with baseline score as covariate, treatment, pooled center, visit and treatment-by-visit interaction as fixed effects.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo	50 mg Etanercept (ETN)	80 mg ixekizumab Dosing Regimen 2 (Q4W)	80 mg ixekizumab Dosing Regimen 1 (Q2W)
Number of subjects analysed	115 ^[29]	233 ^[30]	226 ^[31]	228 ^[32]
Units: Units on a Scale
least squares mean (standard error)	1.6362 ( 1.0991 )	-6.4015 ( 0.7716 )	-9.9793 ( 0.7838 )	-10.4145 ( 0.7820 )

Notes
[29] - All randomized participants with fingernail involvement at baseline and had ≥1 post baseline.
[30] - All randomized participants with fingernail involvement at baseline and had ≥1 post baseline.
[31] - All randomized participants with fingernail involvement at baseline and had ≥1 post baseline.
[32] - All randomized participants with fingernail involvement at baseline and had ≥1 post baseline.

NAPSI Statistical Analysis 1

Comparison groups

50 mg Etanercept (ETN) v Placebo

Number of subjects included in analysis

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Confidence interval

NAPSI Statistical Analysis 2

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 2 (Q4W)

Number of subjects included in analysis

341

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Confidence interval

NAPSI Statistical Analysis 3

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 1 (Q2W)

Number of subjects included in analysis

343

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Confidence interval

Secondary: Percent of Body Surface Area (BSA) Involvement of Psoriasis

Top of page

End point title

Percent of Body Surface Area (BSA) Involvement of Psoriasis

End point description

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

End point type

Secondary

End point timeframe

Week 12

End point values	Placebo	50 mg Etanercept (ETN)	80 mg ixekizumab Dosing Regimen 2 (Q4W)	80 mg ixekizumab Dosing Regimen 1 (Q2W)
Number of subjects analysed	192 ^[33]	378 ^[34]	377 ^[35]	380 ^[36]
Units: Percent
least squares mean (standard error)	-0.7 ( 1.03 )	-16.4 ( 0.73 )	-23.2 ( 0.73 )	-23.2 ( 0.73 )

Notes
[33] - All randomized participants and had at least one post-dose measurement of BSA.
[34] - All randomized participants and had at least one post-dose measurement of BSA.
[35] - All randomized participants and had at least one post-dose measurement of BSA.
[36] - All randomized participants and had at least one post-dose measurement of BSA.

BSA Statistical Analysis 1

Comparison groups

Placebo v 50 mg Etanercept (ETN)

Number of subjects included in analysis

570

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Confidence interval

BSA Statistical Analysis 2

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 2 (Q4W)

Number of subjects included in analysis

569

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Confidence interval

BSA Statistical Analysis 3

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 1 (Q2W)

Number of subjects included in analysis

572

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Confidence interval

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

Top of page

End point title

Change from Baseline in Psoriasis Scalp Severity Index (PSSI) Score

End point description

PSSI is a composite score ranging from 0 (best) to 72 (worst), derived from the sum scores for erythema, induration, and desquamation multiplied by a score for the extent of scalp area involved. LS Means in PSSI score were calculated using MMRM with baseline score as covariate, treatment, pooled center, visit and treatment-by-visit interaction as fixed effects.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo	50 mg Etanercept (ETN)	80 mg ixekizumab Dosing Regimen 2 (Q4W)	80 mg ixekizumab Dosing Regimen 1 (Q2W)
Number of subjects analysed	175 ^[37]	345 ^[38]	344 ^[39]	344 ^[40]
Units: Units on a Scale
least squares mean (standard error)	-5.0 ( 0.53 )	-15.9 ( 0.38 )	-18.2 ( 0.38 )	-18.8 ( 0.38 )

Notes
[37] - All randomized participants and had scalp psoriasis at baseline and had at least one post-dose.
[38] - All randomized participants and had scalp psoriasis at baseline and had at least one post-dose.
[39] - All randomized participants and had scalp psoriasis at baseline and had at least one post-dose.
[40] - All randomized participants and had scalp psoriasis at baseline and had at least one post-dose.

PSSI Statistical Analysis 1

Comparison groups

Placebo v 50 mg Etanercept (ETN)

Number of subjects included in analysis

520

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Confidence interval

PSSI Statistical Analysis 2

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 2 (Q4W)

Number of subjects included in analysis

519

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Confidence interval

PSSI Statistical Analysis 3

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 1 (Q2W)

Number of subjects included in analysis

519

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Confidence interval

Secondary: Change from Baseline in Quick Inventory of Depressive Symptomatology-Self Report 16 Items (QIDS-SR16) Total Score [Quality of Life and Outcome Assessments. Measures: Patient Reported Outcomes (PRO)]

Top of page

End point title

Change from Baseline in Quick Inventory of Depressive Symptomatology-Self Report 16 Items (QIDS-SR16) Total Score [Quality of Life and Outcome Assessments. Measures: Patient Reported Outcomes (PRO)]

End point description

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

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo	50 mg Etanercept (ETN)	80 mg ixekizumab Dosing Regimen 2 (Q4W)	80 mg ixekizumab Dosing Regimen 1 (Q2W)
Number of subjects analysed	184 ^[41]	379 ^[42]	373 ^[43]	373 ^[44]
Units: Units on a Scale
least squares mean (standard error)	-0.3 ( 0.20 )	-0.5 ( 0.14 )	-0.9 ( 0.14 )	-1.3 ( 0.14 )

Notes
[41] - All randomized participants and had at least one post-dose measurement of QIDS-SR16.
[42] - All randomized participants and had at least one post-dose measurement of QIDS-SR16.
[43] - All randomized participants and had at least one post-dose measurement of QIDS-SR16.
[44] - All randomized participants and had at least one post-dose measurement of QIDS-SR16.

QIDS-SR16 Statistical Analysis 1

Comparison groups

50 mg Etanercept (ETN) v Placebo

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.473

Method

ANCOVA

Confidence interval

QIDS-SR16 Statistical Analysis 2

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 2 (Q4W)

Number of subjects included in analysis

557

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.015

Method

ANCOVA

Confidence interval

QIDS-SR16 Statistical Analysis 3

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 1 (Q2W)

Number of subjects included in analysis

557

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Confidence interval

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

Top of page

End point title

Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey, Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores

End point description

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

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo	50 mg Etanercept (ETN)	80 mg ixekizumab Dosing Regimen 2 (Q4W)	80 mg ixekizumab Dosing Regimen 1 (Q2W)
Number of subjects analysed	179 ^[45]	365 ^[46]	362 ^[47]	357 ^[48]
Units: Units on a Scale
least squares mean (standard error)
PCS	-0.2 ( 0.51 )	3.1 ( 0.36 )	4.1 ( 0.36 )	4.0 ( 0.36 )
MCS	1.2 ( 0.58 )	2.7 ( 0.40 )	3.8 ( 0.41 )	4.28 ( 0.41 )

Notes
[45] - All randomized participants and had at least one post-dose measurement of SF-36.
[46] - All randomized participants and had at least one post-dose measurement of SF-36.
[47] - All randomized participants and had at least one post-dose measurement of SF-36.
[48] - All randomized participants and had at least one post-dose measurement of SF-36.

SF-36 Statistical Analysis 1

Comparison groups

Placebo v 50 mg Etanercept (ETN)

Number of subjects included in analysis

544

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Confidence interval

SF-36 Statistical Analysis 2

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 2 (Q4W)

Number of subjects included in analysis

541

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Confidence interval

SF-36 Statistical Analysis 3

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 2 (Q4W)

Number of subjects included in analysis

541

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Confidence interval

SF-36 Statistical Analysis 4

Comparison groups

Placebo v 50 mg Etanercept (ETN)

Number of subjects included in analysis

544

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.031

Method

ANCOVA

Confidence interval

SF-36 Statistical Analysis 5

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 2 (Q4W)

Number of subjects included in analysis

541

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Confidence interval

SF-36 Statistical Analysis 6

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 1 (Q2W)

Number of subjects included in analysis

536

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.01

Method

ANCOVA

Confidence interval

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

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo	50 mg Etanercept (ETN)	80 mg ixekizumab Dosing Regimen 2 (Q4W)	80 mg ixekizumab Dosing Regimen 1 (Q2W)
Number of subjects analysed	192 ^[49]	377 ^[50]	375 ^[51]	376 ^[52]
Units: Units on a Scale
least squares mean (standard error)	-0.5 ( 0.08 )	-2.3 ( 0.06 )	-3.1 ( 0.06 )	-3.1 ( 0.06 )

Notes
[49] - All randomized participants and had at least one post-dose measurement of PatGA.
[50] - All randomized participants and had at least one post-dose measurement of PatGA.
[51] - All randomized participants and had at least one post-dose measurement of PatGA.
[52] - All randomized participants and had at least one post-dose measurement of PatGA.

PatGA Statistical Analysis 1

Comparison groups

Placebo v 50 mg Etanercept (ETN)

Number of subjects included in analysis

569

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Confidence interval

PatGA Statistical Analysis 2

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 2 (Q4W)

Number of subjects included in analysis

567

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Confidence interval

PatGA Statistical Analysis 3

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 1 (Q2W)

Number of subjects included in analysis

568

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Confidence interval

Secondary: Number of Participants Achieving Palmoplantar PASI ≥50% (PPASI 50) Improvement

Top of page

End point title

Number of Participants Achieving Palmoplantar PASI ≥50% (PPASI 50) Improvement

End point description

Palmoplantar PASI is a composite score derived from the sum scores for erythema, induration, and desquamation multiplied by a score for the extent of palm and sole area involvement, ranging from 0 to 72. Participants achieving PPASI 50 were defined as having an improvement of at least 50% in the PPASI scores compared to baseline. Participants who did not meet clinical response criteria or have missing data at Week 12 will be considered non-responders for the NRI analysis.

End point type

Secondary

End point timeframe

Week 12

End point values	Placebo	50 mg Etanercept (ETN)	80 mg ixekizumab Dosing Regimen 2 (Q4W)	80 mg ixekizumab Dosing Regimen 1 (Q2W)
Number of subjects analysed	54 ^[53]	95 ^[54]	87 ^[55]	96 ^[56]
Units: Participants	26	77	75	78

Notes
[53] - All randomized participants and had a diagnosis of palmoplantar psoriasis at baseline.
[54] - All randomized participants and had a diagnosis of palmoplantar psoriasis at baseline.
[55] - All randomized participants and had a diagnosis of palmoplantar psoriasis at baseline.
[56] - All randomized participants and had a diagnosis of palmoplantar psoriasis at baseline.

Statistical Analysis 1 (PPASI 50)

Comparison groups

Placebo v 50 mg Etanercept (ETN)

Number of subjects included in analysis

149

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

Statistical Analysis 2 (PPASI 50)

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 2 (Q4W)

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

Statistical Analysis 3 (PPASI 50)

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 1 (Q2W)

Number of subjects included in analysis

150

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

Secondary: Number of Participants Achieving Palmoplantar PASI of ≥75% (PPASI 75) Improvement

Top of page

End point title

Number of Participants Achieving Palmoplantar PASI of ≥75% (PPASI 75) Improvement

End point description

Palmoplantar PASI is a composite score derived from the sum scores for erythema, induration, and desquamation multiplied by a score for the extent of palm and sole area involvement, ranging from 0 to 72. Participants achieving PPASI 75 were defined as having an improvement of at least 75% in the PPASI scores compared to baseline. Participants who did not meet clinical response criteria or have missing data at Week 12 will be considered non-responders for the NRI analysis.

End point type

Secondary

End point timeframe

Week 12

End point values	Placebo	50 mg Etanercept (ETN)	80 mg ixekizumab Dosing Regimen 2 (Q4W)	80 mg ixekizumab Dosing Regimen 1 (Q2W)
Number of subjects analysed	54 ^[57]	95 ^[58]	87 ^[59]	96 ^[60]
Units: Participants	19	63	69	72

Notes
[57] - All randomized participants and had a diagnosis of palmoplantar psoriasis at baseline.
[58] - All randomized participants and had a diagnosis of palmoplantar psoriasis at baseline.
[59] - All randomized participants and had a diagnosis of palmoplantar psoriasis at baseline.
[60] - All randomized participants and had a diagnosis of palmoplantar psoriasis at baseline.

Statistical Analysis 1 (PPASI 75)

Comparison groups

Placebo v 50 mg Etanercept (ETN)

Number of subjects included in analysis

149

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

Statistical Analysis 2 (PPASI 75)

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 2 (Q4W)

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

Statistical Analysis 3 (PPASI 75)

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 1 (Q2W)

Number of subjects included in analysis

150

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

Secondary: Number of Participants Achieving Palmoplantar PASI of 100% (PPASI 100) Improvement

Top of page

End point title

Number of Participants Achieving Palmoplantar PASI of 100% (PPASI 100) Improvement

End point description

Palmoplantar PASI is a composite score derived from the sum scores for erythema, induration, and desquamation multiplied by a score for the extent of palm and sole area involvement, ranging from 0 to 72. Participants achieving PPASI 100 were defined as having an improvement of 100% in the PPASI scores compared to baseline. Participants who did not meet clinical response criteria or have missing data at Week 12 will be considered non-responders for the NRI analysis.

End point type

Secondary

End point timeframe

Week 12

End point values	Placebo	50 mg Etanercept (ETN)	80 mg ixekizumab Dosing Regimen 2 (Q4W)	80 mg ixekizumab Dosing Regimen 1 (Q2W)
Number of subjects analysed	54 ^[61]	95 ^[62]	87 ^[63]	96 ^[64]
Units: Participants	15	57	54	61

Notes
[61] - All randomized participants and had a diagnosis of palmoplantar psoriasis at baseline.
[62] - All randomized participants and had a diagnosis of palmoplantar psoriasis at baseline.
[63] - All randomized participants and had a diagnosis of palmoplantar psoriasis at baseline.
[64] - All randomized participants and had a diagnosis of palmoplantar psoriasis at baseline.

Statistical Analysis 1 (PPASI 100)

Comparison groups

Placebo v 50 mg Etanercept (ETN)

Number of subjects included in analysis

149

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

Statistical Analysis 2 (PPASI 100)

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 2 (Q4W)

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

Statistical Analysis 3 (PPASI 100)

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 1 (Q2W)

Number of subjects included in analysis

150

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Confidence interval

Secondary: Number of Participants With Treatment-Emergent Anti-Ixekizumab Antibodies

Top of page

End point title

Number of Participants With Treatment-Emergent Anti-Ixekizumab Antibodies

End point description

The percentage of participants with treatment-emergent positive anti-ixekizumab antibodies at any time post-baseline were summarized by treatment group. Percentage of participants with treatment-emergent positive anti-ixekizumab antibodies were calculated as: number of participants with an evaluable baseline sample and ≥1 evaluable post-baseline sample/number of participants in the analysis population * 100.

End point type

Secondary

End point timeframe

Week 12

End point values	Placebo	50 mg Etanercept (ETN)	80 mg ixekizumab Dosing Regimen 2 (Q4W)	80 mg ixekizumab Dosing Regimen 1 (Q2W)
Number of subjects analysed	191 ^[65]	378 ^[66]	378 ^[67]	378 ^[68]
Units: Participants	2	8	52	23

Notes
[65] - All randomized participants who received at least one dose of study treatment and had evaluable data
[66] - All randomized participants who received at least one dose of study treatment and had evaluable data
[67] - All randomized participants who received at least one dose of study treatment and had evaluable data
[68] - All randomized participants who received at least one dose of study treatment and had evaluable data

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

The WPAI-PSO is a 6-item instrument used to assess the impact of psoriasis on productivity impairment within the past 7 days. It has four 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, overall work impairment (absenteeism and presenteeism), and impairment in activities performed outside of work. Percentage is calculated as: each score * 100 and ranged from 0 to 100. Higher scores indicate greater impairment in productivity. LS Means in each WPAI-PSO score were calculated using the ANCOVA model with treatment, pooled center and baseline WPAI-PSO score. Missing data was imputed by last observation carried forward (LOCF).

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo	50 mg Etanercept (ETN)	80 mg ixekizumab Dosing Regimen 2 (Q4W)	80 mg ixekizumab Dosing Regimen 1 (Q2W)
Number of subjects analysed	120 ^[69]	217 ^[70]	230 ^[71]	218 ^[72]
Units: Units on a Scale
least squares mean (standard error)	0.0 ( 0.82 )	-2.8 ( 0.62 )	-2.0 ( 0.60 )	-2.5 ( 0.61 )

Notes
[69] - All randomized participants and had a least one post-dose measurement of WPAI-PSO.
[70] - All randomized participants and had a least one post-dose measurement of WPAI-PSO.
[71] - All randomized participants and had a least one post-dose measurement of WPAI-PSO.
[72] - All randomized participants and had a least one post-dose measurement of WPAI-PSO.

WPAI-PSO Statistical Analysis 1

Statistical analysis description

Absenteeism Score

Comparison groups

Placebo v 50 mg Etanercept (ETN)

Number of subjects included in analysis

337

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006

Method

ANCOVA

Confidence interval

WPAI-PSO Statistical Analysis 2

Statistical analysis description

Absenteeism Score

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 2 (Q4W)

Number of subjects included in analysis

350

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.045

Method

ANCOVA

Confidence interval

WPAI-PSO Statistical Analysis 3

Statistical analysis description

Absenteeism Score

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 1 (Q2W)

Number of subjects included in analysis

338

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.012

Method

ANCOVA

Confidence interval

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

Top of page

End point title

Change From Baseline in Activity Impairment Score of WPAI-PSO

End point description

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo	50 mg Etanercept (ETN)	80 mg ixekizumab Dosing Regimen 2 (Q4W)	80 mg ixekizumab Dosing Regimen 1 (Q2W)
Number of subjects analysed	184 ^[73]	376 ^[74]	375 ^[75]	373 ^[76]
Units: Units on a Scale
least squares mean (standard error)	-2.5 ( 1.30 )	-21.1 ( 0.91 )	-23.3 ( 0.92 )	-24.5 ( 0.92 )

Notes
[73] - All randomized participants and had at least one post-dose measurement of WPAI-PSO.
[74] - All randomized participants and had at least one post-dose measurement of WPAI-PSO.
[75] - All randomized participants and had at least one post-dose measurement of WPAI-PSO.
[76] - All randomized participants and had at least one post-dose measurement of WPAI-PSO.

WPAI-PSO Statistical Analysis 4

Statistical analysis description

Activity Impairment Score

Comparison groups

50 mg Etanercept (ETN) v Placebo

Number of subjects included in analysis

560

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Confidence interval

WPAI-PSO Statistical Analysis 5

Statistical analysis description

Activity Impairment Score

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 2 (Q4W)

Number of subjects included in analysis

559

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Confidence interval

WPAI-PSO Statistical Analysis 6

Statistical analysis description

Activity Impairment Score

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 1 (Q2W)

Number of subjects included in analysis

557

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Confidence interval

Secondary: Change From Baseline in Presenteeism of WPAI-PSO

Top of page

End point title

Change From Baseline in Presenteeism of WPAI-PSO

End point description

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo	50 mg Etanercept (ETN)	80 mg ixekizumab Dosing Regimen 2 (Q4W)	80 mg ixekizumab Dosing Regimen 1 (Q2W)
Number of subjects analysed	137 ^[77]	243 ^[78]	256 ^[79]	242 ^[80]
Units: Units on a Scale
least squares mean (standard error)	-0.8 ( 1.37 )	-16.4 ( 1.04 )	-16.0 ( 1.01 )	-18.1 ( 1.04 )

Notes
[77] - All randomized participants and had at least one post-dose measurement of WPAI-PSO.
[78] - All randomized participants and had at least one post-dose measurement of WPAI-PSO.
[79] - All randomized participants and had at least one post-dose measurement of WPAI-PSO.
[80] - All randomized participants and had at least one post-dose measurement of WPAI-PSO.

WPAI-PSO Statistical Analysis 7

Statistical analysis description

Presenteeism Score

Comparison groups

Placebo v 50 mg Etanercept (ETN)

Number of subjects included in analysis

380

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.01

Method

ANCOVA

Confidence interval

WPAI-PSO Statistical Analysis 8

Statistical analysis description

Presenteeism

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 2 (Q4W)

Number of subjects included in analysis

393

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Confidence interval

WPAI-PSO Statistical Analysis 9

Statistical analysis description

Presenteeism Score

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 1 (Q2W)

Number of subjects included in analysis

379

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Confidence interval

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

Top of page

End point title

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

End point description

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo	50 mg Etanercept (ETN)	80 mg ixekizumab Dosing Regimen 2 (Q4W)	80 mg ixekizumab Dosing Regimen 1 (Q2W)
Number of subjects analysed	120 ^[81]	216 ^[82]	228 ^[83]	216 ^[84]
Units: Units on a Scale
least squares mean (standard error)	0.6 ( 1.59 )	-17.4 ( 1.20 )	-16.7 ( 1.16 )	-19.3 ( 1.19 )

Notes
[81] - All randomized participants and had at least one post-dose measurement of WPAI-PSO.
[82] - All randomized participants and had at least one post-dose measurement of WPAI-PSO.
[83] - All randomized participants and had at least one post-dose measurement of WPAI-PSO.
[84] - All randomized participants and had at least one post-dose measurement of WPAI-PSO.

WPAI-PSO Statistical Analysis 10

Statistical analysis description

Work Productively Loss Score

Comparison groups

Placebo v 50 mg Etanercept (ETN)

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Confidence interval

WPAI-PSO Statistical Analysis 11

Statistical analysis description

Work Productively Loss Score

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 2 (Q4W)

Number of subjects included in analysis

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Confidence interval

WPAI-PSO Statistical Analysis 12

Statistical analysis description

Work Productively Loss Score

Comparison groups

Placebo v 80 mg ixekizumab Dosing Regimen 1 (Q2W)

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Confidence interval

Adverse events

Top of page

Timeframe for reporting adverse events

Induction, Long Term Extension and Follow-Up Periods

Adverse event reporting additional description

I1F-MC-RHBC

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

22.0

Reporting group title

Placebo

Reporting group description

Reporting group title

50 mg Etanercept

Reporting group description

Reporting group title

80 mg Ixekizumab Dosing Regimen 2 (Q4W)

Reporting group description

Reporting group title

80 mg Ixekizumab Dosing Regimen 1 (Q2W)

Reporting group description

Reporting group title

PBO/IXE80Q4W Long term extension

Reporting group description

Reporting group title

ETN/IXE80Q4W Long term extension

Reporting group description

Reporting group title

IXE80Q4W/IXE80Q4W Long term extension

Reporting group description

Reporting group title

IXE80Q2W/IXE80Q4W Long term extension

Reporting group description

Reporting group title

PBO follow-up period

Reporting group description

Reporting group title

ETN follow-up period

Reporting group description

Reporting group title

IXE80Q4W follow-up period

Reporting group description

Reporting group title

IXE80Q2W follow-up period

Reporting group description

Placebo

50 mg Etanercept

80 mg Ixekizumab Dosing Regimen 2 (Q4W)

80 mg Ixekizumab Dosing Regimen 1 (Q2W)

PBO/IXE80Q4W Long term extension

ETN/IXE80Q4W Long term extension

IXE80Q4W/IXE80Q4W Long term extension

IXE80Q2W/IXE80Q4W Long term extension

PBO follow-up period

ETN follow-up period

IXE80Q4W follow-up period

IXE80Q2W follow-up period

Total subjects affected by serious adverse events

subjects affected / exposed

5 / 193 (2.59%)

8 / 382 (2.09%)

6 / 382 (1.57%)

9 / 384 (2.34%)

45 / 183 (24.59%)

71 / 369 (19.24%)

82 / 360 (22.78%)

55 / 362 (15.19%)

5 / 157 (3.18%)

5 / 309 (1.62%)

2 / 305 (0.66%)

6 / 313 (1.92%)

number of deaths (all causes)

number of deaths resulting from adverse events

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

basal cell carcinoma

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

2 / 360 (0.56%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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

benign lung neoplasm

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

benign neoplasm of thyroid gland

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

bone cancer metastatic

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

breast cancer

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

carcinoid tumour of the duodenum

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cholesteatoma

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ewing's sarcoma metastatic

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

gallbladder cancer

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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

hepatic adenoma

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

1 / 382 (0.26%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

hodgkin's disease

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

hodgkin's disease mixed cellularity stage unspecified

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

invasive breast carcinoma

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

lung neoplasm

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

metastases to central nervous system

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

metastases to liver

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

metastases to lung

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

2 / 369 (0.54%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

myelodysplastic syndrome

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

non-hodgkin's lymphoma

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

oesophageal adenocarcinoma

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ovarian germ cell teratoma benign

alternative dictionary used: MedDRA 22.0

subjects affected / exposed ^[1]

0 / 56 (0.00%)

0 / 113 (0.00%)

0 / 128 (0.00%)

0 / 130 (0.00%)

0 / 54 (0.00%)

1 / 109 (0.92%)

0 / 119 (0.00%)

0 / 121 (0.00%)

0 / 49 (0.00%)

0 / 92 (0.00%)

0 / 100 (0.00%)

0 / 104 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pituitary tumour benign

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

prostate cancer

alternative dictionary used: MedDRA 22.0

subjects affected / exposed ^[2]

0 / 137 (0.00%)

0 / 269 (0.00%)

0 / 254 (0.00%)

0 / 129 (0.00%)

1 / 260 (0.38%)

2 / 241 (0.83%)

0 / 108 (0.00%)

0 / 217 (0.00%)

0 / 205 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 2

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

prostate cancer metastatic

alternative dictionary used: MedDRA 22.0

subjects affected / exposed ^[3]

0 / 137 (0.00%)

0 / 269 (0.00%)

0 / 254 (0.00%)

0 / 129 (0.00%)

0 / 260 (0.00%)

1 / 241 (0.41%)

0 / 241 (0.00%)

0 / 108 (0.00%)

0 / 217 (0.00%)

0 / 205 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

rectal adenocarcinoma

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

rectal adenoma

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

1 / 313 (0.32%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

renal cell carcinoma stage ii

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

synovial sarcoma

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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

uterine leiomyoma

alternative dictionary used: MedDRA 22.0

subjects affected / exposed ^[4]

0 / 56 (0.00%)

1 / 113 (0.88%)

0 / 128 (0.00%)

0 / 130 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 119 (0.00%)

1 / 121 (0.83%)

0 / 49 (0.00%)

0 / 92 (0.00%)

0 / 100 (0.00%)

0 / 104 (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

vulval cancer metastatic

alternative dictionary used: MedDRA 22.0

subjects affected / exposed ^[5]

0 / 56 (0.00%)

0 / 113 (0.00%)

0 / 128 (0.00%)

0 / 130 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

1 / 119 (0.84%)

0 / 121 (0.00%)

0 / 49 (0.00%)

0 / 92 (0.00%)

0 / 100 (0.00%)

0 / 104 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

air embolism

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

aortic aneurysm

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

deep vein thrombosis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

2 / 362 (0.55%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

diabetic vascular disorder

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

hypertension

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

hypertensive crisis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

peripheral arterial occlusive disease

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Surgical and medical procedures

coronary artery bypass

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

fracture treatment

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

gastric bypass

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

hernia repair

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

hysterectomy

alternative dictionary used: MedDRA 22.0

subjects affected / exposed ^[6]

0 / 56 (0.00%)

0 / 113 (0.00%)

0 / 128 (0.00%)

0 / 130 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

1 / 119 (0.84%)

0 / 121 (0.00%)

0 / 49 (0.00%)

0 / 92 (0.00%)

0 / 100 (0.00%)

0 / 104 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

implantable cardiac monitor insertion

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

1 / 157 (0.64%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

perineal operation

alternative dictionary used: MedDRA 22.0

subjects affected / exposed ^[7]

0 / 56 (0.00%)

0 / 113 (0.00%)

0 / 128 (0.00%)

0 / 130 (0.00%)

0 / 54 (0.00%)

1 / 109 (0.92%)

0 / 119 (0.00%)

0 / 121 (0.00%)

0 / 49 (0.00%)

0 / 92 (0.00%)

0 / 100 (0.00%)

0 / 104 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pregnancy, puerperium and perinatal conditions

abortion spontaneous

alternative dictionary used: MedDRA 22.0

subjects affected / exposed ^[8]

0 / 56 (0.00%)

0 / 113 (0.00%)

0 / 128 (0.00%)

0 / 130 (0.00%)

0 / 54 (0.00%)

1 / 109 (0.92%)

2 / 119 (1.68%)

0 / 121 (0.00%)

0 / 49 (0.00%)

1 / 92 (1.09%)

0 / 100 (0.00%)

0 / 104 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

polyhydramnios

alternative dictionary used: MedDRA 22.0

subjects affected / exposed ^[9]

0 / 56 (0.00%)

0 / 113 (0.00%)

0 / 128 (0.00%)

0 / 130 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 119 (0.00%)

0 / 121 (0.00%)

0 / 49 (0.00%)

0 / 92 (0.00%)

1 / 100 (1.00%)

0 / 104 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

premature baby

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

1 / 305 (0.33%)

0 / 313 (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

accidental death

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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

chest discomfort

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

chest pain

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 4

0 / 0

deaths causally related to treatment / all

0 / 0

death

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

hernia

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

non-cardiac chest pain

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Immune system disorders

hypersensitivity

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

sarcoidosis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Reproductive system and breast disorders

benign prostatic hyperplasia

alternative dictionary used: MedDRA 22.0

subjects affected / exposed ^[10]

0 / 137 (0.00%)

0 / 269 (0.00%)

0 / 254 (0.00%)

0 / 129 (0.00%)

1 / 260 (0.38%)

0 / 241 (0.00%)

0 / 108 (0.00%)

0 / 217 (0.00%)

0 / 205 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

breast disorder

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

genital haemorrhage

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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 22.0

subjects affected / exposed ^[11]

0 / 56 (0.00%)

1 / 113 (0.88%)

0 / 128 (0.00%)

0 / 130 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 119 (0.00%)

0 / 121 (0.00%)

0 / 49 (0.00%)

0 / 92 (0.00%)

0 / 100 (0.00%)

0 / 104 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

prostatitis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed ^[12]

0 / 137 (0.00%)

0 / 269 (0.00%)

1 / 254 (0.39%)

0 / 254 (0.00%)

0 / 129 (0.00%)

0 / 260 (0.00%)

0 / 241 (0.00%)

0 / 108 (0.00%)

0 / 217 (0.00%)

0 / 205 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

uterine scar

alternative dictionary used: MedDRA 22.0

subjects affected / exposed ^[13]

0 / 56 (0.00%)

0 / 113 (0.00%)

0 / 128 (0.00%)

0 / 130 (0.00%)

0 / 54 (0.00%)

0 / 109 (0.00%)

0 / 119 (0.00%)

1 / 121 (0.83%)

0 / 49 (0.00%)

0 / 92 (0.00%)

0 / 100 (0.00%)

0 / 104 (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

acute respiratory failure

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

chronic obstructive pulmonary disease

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

2 / 369 (0.54%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 3

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

hypoxia

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

lung consolidation

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

nasal polyps

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

nasal septum deviation

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

2 / 183 (1.09%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

nasal turbinate hypertrophy

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pleural effusion

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pulmonary embolism

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

1 / 305 (0.33%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pulmonary oedema

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

respiratory failure

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

sleep apnoea syndrome

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Psychiatric disorders

acute stress disorder

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

alcohol abuse

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

anxiety

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

1 / 384 (0.26%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

bipolar i disorder

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

bipolar disorder

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

1 / 193 (0.52%)

0 / 382 (0.00%)

1 / 384 (0.26%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

1 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

burnout syndrome

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

confusional state

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

depression

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

1 / 384 (0.26%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

2 / 362 (0.55%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 1

0 / 0

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

hallucination

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

major depression

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

1 / 157 (0.64%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

psychotic disorder

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

suicidal ideation

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

suicide attempt

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

1 / 157 (0.64%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Investigations

alanine aminotransferase increased

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

aspartate aminotransferase increased

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

biopsy liver

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

blood alkaline phosphatase increased

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

blood bilirubin increased

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

gamma-glutamyltransferase increased

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

glomerular filtration rate decreased

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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

accident

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

accident at work

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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

alcohol poisoning

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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

avulsion fracture

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

carotid artery restenosis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

chemical burn of skin

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

clavicle fracture

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

3 / 362 (0.83%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 4

0 / 0

deaths causally related to treatment / all

0 / 0

concussion

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

contusion

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

fall

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

1 / 193 (0.52%)

1 / 382 (0.26%)

0 / 382 (0.00%)

1 / 384 (0.26%)

2 / 183 (1.09%)

2 / 369 (0.54%)

2 / 360 (0.56%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

1 / 313 (0.32%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 2

0 / 3

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

femoral neck fracture

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

femur fracture

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

hand fracture

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

incision site haemorrhage

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

incisional hernia

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

joint dislocation

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

lower limb fracture

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

1 / 313 (0.32%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

meniscus injury

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

1 / 382 (0.26%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

3 / 360 (0.83%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 4

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

patella fracture

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pelvic fracture

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

post procedural bile leak

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

procedural pain

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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

rib fracture

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

2 / 362 (0.55%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

seroma

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

skull fracture

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

subdural haematoma

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

1 / 384 (0.26%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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 22.0

subjects affected / exposed

1 / 193 (0.52%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

upper limb fracture

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

wound

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

wound dehiscence

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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

Congenital, familial and genetic disorders

laryngocele

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

acute myocardial infarction

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

1 / 193 (0.52%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

2 / 369 (0.54%)

2 / 360 (0.56%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

angina pectoris

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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

angina unstable

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

2 / 369 (0.54%)

0 / 360 (0.00%)

2 / 362 (0.55%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

arteriosclerosis coronary artery

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

1 / 313 (0.32%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

atrial fibrillation

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

2 / 183 (1.09%)

3 / 369 (0.81%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 11

0 / 0

deaths causally related to treatment / all

0 / 0

atrial flutter

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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

bradycardia

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cardiac arrest

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cardiac failure acute

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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

cardiac failure congestive

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cardio-respiratory arrest

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

coronary artery disease

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

2 / 360 (0.56%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

coronary artery stenosis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

left ventricular failure

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

myocardial infarction

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

2 / 183 (1.09%)

2 / 369 (0.54%)

3 / 360 (0.83%)

2 / 362 (0.55%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

1 / 2

1 / 4

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

myocardial ischaemia

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

2 / 360 (0.56%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

myocarditis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

palpitations

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

2 / 369 (0.54%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

pericarditis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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

cerebral artery embolism

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

1 / 382 (0.26%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

1 / 309 (0.32%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cerebral haemorrhage

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

1 / 157 (0.64%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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

0 / 1

0 / 0

cerebrovascular accident

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

2 / 369 (0.54%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

1 / 309 (0.32%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cervicobrachial syndrome

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 4

0 / 0

deaths causally related to treatment / all

0 / 0

dizziness

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

embolic stroke

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

epilepsy

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

facial paralysis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

haemorrhagic cerebral infarction

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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

headache

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

hemiparesis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

1 / 157 (0.64%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

hepatic encephalopathy

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

lacunar infarction

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

loss of consciousness

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

miller fisher syndrome

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

paraesthesia

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

reversible ischaemic neurological deficit

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

sciatica

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

senile dementia

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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

syncope

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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

iron deficiency anaemia

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Ear and labyrinth disorders

vertigo

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

1 / 369 (0.27%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Eye disorders

cataract

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

1 / 382 (0.26%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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

conjunctivitis allergic

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

diplopia

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

optic ischaemic neuropathy

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

retinal vein thrombosis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

anal fissure

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

colitis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

2 / 360 (0.56%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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

colitis microscopic

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

1 / 305 (0.33%)

0 / 313 (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

1 / 1

0 / 0

crohn's disease

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

1 / 384 (0.26%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

1 / 313 (0.32%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

diarrhoea

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

2 / 362 (0.55%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

diverticulum oesophageal

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

gastric polyps

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

gastritis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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

gastrooesophageal reflux disease

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

2 / 360 (0.56%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 4

0 / 0

deaths causally related to treatment / all

0 / 0

haematemesis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

1 / 157 (0.64%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

haematochezia

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

haemorrhoidal haemorrhage

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

haemorrhoids

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

inguinal hernia

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

1 / 193 (0.52%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

intussusception

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

large intestinal haemorrhage

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

large intestine polyp

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

lower gastrointestinal haemorrhage

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

nausea

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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

pancreatitis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pancreatitis acute

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

1 / 382 (0.26%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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

pancreatitis necrotising

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

rectal haemorrhage

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

upper gastrointestinal haemorrhage

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

vomiting

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

bile duct obstruction

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

biliary colic

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

2 / 183 (1.09%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

1 / 313 (0.32%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

cholecystitis acute

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

2 / 369 (0.54%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

cholelithiasis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

1 / 384 (0.26%)

0 / 183 (0.00%)

2 / 369 (0.54%)

4 / 360 (1.11%)

4 / 362 (1.10%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

1 / 313 (0.32%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 4

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

hepatic function abnormal

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

1 / 384 (0.26%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

hepatic steatosis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

jaundice cholestatic

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

non-alcoholic steatohepatitis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Skin and subcutaneous tissue disorders

diabetic ulcer

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

hypersensitivity vasculitis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

1 / 384 (0.26%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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

palmoplantar keratoderma

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

1 / 193 (0.52%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

psoriasis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

1 / 193 (0.52%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

2 / 309 (0.65%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

skin lesion

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

1 / 384 (0.26%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

skin ulcer

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

urticaria

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

acute kidney injury

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

1 / 382 (0.26%)

0 / 384 (0.00%)

1 / 183 (0.55%)

2 / 369 (0.54%)

2 / 360 (0.56%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

1 / 2

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

calculus urinary

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

nephrolithiasis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

1 / 382 (0.26%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

2 / 369 (0.54%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

1 / 313 (0.32%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 3

0 / 0

2 / 2

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

nephrotic syndrome

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

renal artery arteriosclerosis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

renal cyst haemorrhage

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

renal impairment

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

1 / 384 (0.26%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ureterolithiasis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

urinary incontinence

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

arthralgia

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

arthritis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

1 / 384 (0.26%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

3 / 3

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

back pain

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

2 / 183 (1.09%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 11

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

chondrocalcinosis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

intervertebral disc protrusion

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

2 / 183 (1.09%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

knee deformity

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

neck pain

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

osteoarthritis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

1 / 382 (0.26%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

4 / 369 (1.08%)

4 / 360 (1.11%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 8

0 / 7

0 / 6

0 / 7

0 / 0

deaths causally related to treatment / all

0 / 0

osteonecrosis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

plica syndrome

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

psoriatic arthropathy

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

1 / 157 (0.64%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 5

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

rheumatic disorder

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

spinal pain

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

spondylolisthesis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

synovial cyst

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

2 / 360 (0.56%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

synovitis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

3 / 360 (0.83%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 4

0 / 0

deaths causally related to treatment / all

0 / 0

vertebral foraminal stenosis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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 limb

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

anal abscess

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

appendicitis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

1 / 384 (0.26%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

appendicitis perforated

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

breast abscess

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 5

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

bronchitis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

campylobacter infection

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cellulitis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

1 / 193 (0.52%)

0 / 382 (0.00%)

0 / 384 (0.00%)

3 / 183 (1.64%)

4 / 369 (1.08%)

3 / 360 (0.83%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

3 / 3

2 / 4

1 / 3

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cellulitis staphylococcal

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cholecystitis infective

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

chronic sinusitis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

chronic tonsillitis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

1 / 382 (0.26%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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

clostridium difficile colitis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

colonic abscess

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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

cystitis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

device related infection

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

diabetic foot infection

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

diverticulitis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

3 / 183 (1.64%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

erysipelas

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

1 / 382 (0.26%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

2 / 360 (0.56%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

escherichia sepsis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

gas gangrene

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

gastroenteritis escherichia coli

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

groin abscess

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

infection

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

influenza

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

liver abscess

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

mastoiditis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

orchitis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed ^[14]

0 / 137 (0.00%)

0 / 269 (0.00%)

0 / 254 (0.00%)

0 / 129 (0.00%)

0 / 260 (0.00%)

1 / 241 (0.41%)

0 / 241 (0.00%)

0 / 108 (0.00%)

0 / 217 (0.00%)

0 / 205 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

osteomyelitis acute

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pneumonia

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

3 / 360 (0.83%)

1 / 362 (0.28%)

1 / 157 (0.64%)

0 / 309 (0.00%)

1 / 305 (0.33%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

1 / 3

1 / 1

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pneumonia chlamydial

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pulmonary tuberculosis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pyelonephritis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pyelonephritis acute

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

1 / 382 (0.26%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pyonephrosis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

sepsis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

sinusitis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

2 / 360 (0.56%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

skin bacterial infection

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

1 / 193 (0.52%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

soft tissue infection

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

spinal cord abscess

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

staphylococcal infection

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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

streptococcal sepsis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

tonsillitis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

tooth abscess

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

1 / 309 (0.32%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

urinary tract infection

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

3 / 369 (0.81%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 3

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

urinary tract infection bacterial

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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 pseudomonal

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

urosepsis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

1 / 382 (0.26%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Metabolism and nutrition disorders

dehydration

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

1 / 384 (0.26%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

1 / 313 (0.32%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

diabetic ketoacidosis

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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

diabetic metabolic decompensation

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

hyperinsulinaemia

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

hypoglycaemia

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

1 / 360 (0.28%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

obesity

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

1 / 369 (0.27%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

type 1 diabetes mellitus

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

1 / 183 (0.55%)

0 / 369 (0.00%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (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 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

2 / 369 (0.54%)

0 / 360 (0.00%)

0 / 362 (0.00%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

vitamin b12 deficiency

alternative dictionary used: MedDRA 22.0

subjects affected / exposed

0 / 193 (0.00%)

0 / 382 (0.00%)

0 / 384 (0.00%)

0 / 183 (0.00%)

0 / 369 (0.00%)

0 / 360 (0.00%)

1 / 362 (0.28%)

0 / 157 (0.00%)

0 / 309 (0.00%)

0 / 305 (0.00%)

0 / 313 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male and female subjects. The number of subjects exposed has been adjusted accordingly.
[2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male and female subjects. The number of subjects exposed has been adjusted accordingly.
[3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male and female subjects. The number of subjects exposed has been adjusted accordingly.
[4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male and female subjects. The number of subjects exposed has been adjusted accordingly.
[5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male and female subjects. The number of subjects exposed has been adjusted accordingly.
[6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male and female subjects. The number of subjects exposed has been adjusted accordingly.
[7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male and female subjects. The number of subjects exposed has been adjusted accordingly.
[8] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male and female subjects. The number of subjects exposed has been adjusted accordingly.
[9] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male and female subjects. The number of subjects exposed has been adjusted accordingly.
[10] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male and female subjects. The number of subjects exposed has been adjusted accordingly.
[11] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male and female subjects. The number of subjects exposed has been adjusted accordingly.
[12] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male and female subjects. The number of subjects exposed has been adjusted accordingly.
[13] - 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.
[14] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male and female subjects. The number of subjects exposed has been adjusted accordingly.

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

Non-serious adverse events	Placebo	50 mg Etanercept	80 mg Ixekizumab Dosing Regimen 2 (Q4W)	80 mg Ixekizumab Dosing Regimen 1 (Q2W)	PBO/IXE80Q4W Long term extension	ETN/IXE80Q4W Long term extension	IXE80Q4W/IXE80Q4W Long term extension	IXE80Q2W/IXE80Q4W Long term extension	PBO follow-up period	ETN follow-up period	IXE80Q4W follow-up period	IXE80Q2W follow-up period
Total subjects affected by non serious adverse events
subjects affected / exposed	40 / 193 (20.73%)	90 / 382 (23.56%)	115 / 382 (30.10%)	123 / 384 (32.03%)	117 / 183 (63.93%)	240 / 369 (65.04%)	236 / 360 (65.56%)	249 / 362 (68.78%)	9 / 157 (5.73%)	23 / 309 (7.44%)	14 / 305 (4.59%)	15 / 313 (4.79%)
Vascular disorders
hypertension
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	2 / 193 (1.04%)	9 / 382 (2.36%)	3 / 382 (0.79%)	5 / 384 (1.30%)	20 / 183 (10.93%)	30 / 369 (8.13%)	30 / 360 (8.33%)	26 / 362 (7.18%)	1 / 157 (0.64%)	2 / 309 (0.65%)	0 / 305 (0.00%)	0 / 313 (0.00%)
occurrences all number	2	9	3	6	24	42	31	31	1	2	0	0
Nervous system disorders
headache
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	5 / 193 (2.59%)	11 / 382 (2.88%)	16 / 382 (4.19%)	16 / 384 (4.17%)	9 / 183 (4.92%)	30 / 369 (8.13%)	23 / 360 (6.39%)	27 / 362 (7.46%)	0 / 157 (0.00%)	2 / 309 (0.65%)	1 / 305 (0.33%)	2 / 313 (0.64%)
occurrences all number	10	15	23	20	15	47	27	39	0	2	1	2
General disorders and administration site conditions
injection site reaction
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	3 / 193 (1.55%)	42 / 382 (10.99%)	43 / 382 (11.26%)	37 / 384 (9.64%)	18 / 183 (9.84%)	24 / 369 (6.50%)	34 / 360 (9.44%)	24 / 362 (6.63%)	0 / 157 (0.00%)	0 / 309 (0.00%)	0 / 305 (0.00%)	0 / 313 (0.00%)
occurrences all number	21	207	99	111	102	186	291	169	0	0	0	0
Gastrointestinal disorders
diarrhoea
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	2 / 193 (1.04%)	6 / 382 (1.57%)	3 / 382 (0.79%)	11 / 384 (2.86%)	10 / 183 (5.46%)	27 / 369 (7.32%)	14 / 360 (3.89%)	25 / 362 (6.91%)	0 / 157 (0.00%)	0 / 309 (0.00%)	0 / 305 (0.00%)	0 / 313 (0.00%)
occurrences all number	2	6	7	12	12	29	18	32	0	0	0	0
Respiratory, thoracic and mediastinal disorders
cough
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 193 (0.00%)	4 / 382 (1.05%)	9 / 382 (2.36%)	6 / 384 (1.56%)	11 / 183 (6.01%)	23 / 369 (6.23%)	14 / 360 (3.89%)	26 / 362 (7.18%)	0 / 157 (0.00%)	0 / 309 (0.00%)	1 / 305 (0.33%)	0 / 313 (0.00%)
occurrences all number	0	4	10	6	17	29	18	29	0	0	1	0
oropharyngeal pain
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	3 / 193 (1.55%)	2 / 382 (0.52%)	6 / 382 (1.57%)	4 / 384 (1.04%)	10 / 183 (5.46%)	16 / 369 (4.34%)	14 / 360 (3.89%)	16 / 362 (4.42%)	0 / 157 (0.00%)	0 / 309 (0.00%)	0 / 305 (0.00%)	0 / 313 (0.00%)
occurrences all number	3	2	8	4	16	16	18	20	0	0	0	0
Skin and subcutaneous tissue disorders
pruritus
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 193 (0.52%)	4 / 382 (1.05%)	8 / 382 (2.09%)	7 / 384 (1.82%)	2 / 183 (1.09%)	20 / 369 (5.42%)	17 / 360 (4.72%)	10 / 362 (2.76%)	0 / 157 (0.00%)	0 / 309 (0.00%)	0 / 305 (0.00%)	0 / 313 (0.00%)
occurrences all number	1	4	9	9	2	25	22	10	0	0	0	0
psoriasis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	3 / 193 (1.55%)	0 / 382 (0.00%)	5 / 382 (1.31%)	5 / 384 (1.30%)	12 / 183 (6.56%)	17 / 369 (4.61%)	17 / 360 (4.72%)	15 / 362 (4.14%)	3 / 157 (1.91%)	10 / 309 (3.24%)	1 / 305 (0.33%)	4 / 313 (1.28%)
occurrences all number	3	0	6	5	14	22	28	17	3	10	1	4
Musculoskeletal and connective tissue disorders
arthralgia
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	4 / 193 (2.07%)	7 / 382 (1.83%)	9 / 382 (2.36%)	13 / 384 (3.39%)	17 / 183 (9.29%)	20 / 369 (5.42%)	29 / 360 (8.06%)	41 / 362 (11.33%)	0 / 157 (0.00%)	1 / 309 (0.32%)	1 / 305 (0.33%)	1 / 313 (0.32%)
occurrences all number	5	7	9	14	17	24	38	60	0	1	1	1
back pain
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	2 / 193 (1.04%)	2 / 382 (0.52%)	8 / 382 (2.09%)	7 / 384 (1.82%)	16 / 183 (8.74%)	28 / 369 (7.59%)	23 / 360 (6.39%)	30 / 362 (8.29%)	1 / 157 (0.64%)	1 / 309 (0.32%)	0 / 305 (0.00%)	0 / 313 (0.00%)
occurrences all number	2	3	8	8	19	32	33	34	1	1	0	0
Infections and infestations
bronchitis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 193 (0.00%)	4 / 382 (1.05%)	6 / 382 (1.57%)	1 / 384 (0.26%)	17 / 183 (9.29%)	20 / 369 (5.42%)	24 / 360 (6.67%)	36 / 362 (9.94%)	0 / 157 (0.00%)	0 / 309 (0.00%)	1 / 305 (0.33%)	3 / 313 (0.96%)
occurrences all number	0	4	6	1	24	23	32	47	0	0	1	3
gastroenteritis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 193 (0.00%)	2 / 382 (0.52%)	2 / 382 (0.52%)	3 / 384 (0.78%)	12 / 183 (6.56%)	12 / 369 (3.25%)	5 / 360 (1.39%)	18 / 362 (4.97%)	0 / 157 (0.00%)	0 / 309 (0.00%)	0 / 305 (0.00%)	0 / 313 (0.00%)
occurrences all number	0	2	2	3	16	13	5	18	0	0	0	0
influenza
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 193 (0.00%)	1 / 382 (0.26%)	1 / 382 (0.26%)	3 / 384 (0.78%)	11 / 183 (6.01%)	20 / 369 (5.42%)	21 / 360 (5.83%)	20 / 362 (5.52%)	0 / 157 (0.00%)	1 / 309 (0.32%)	0 / 305 (0.00%)	1 / 313 (0.32%)
occurrences all number	0	1	1	3	16	20	23	21	0	1	0	1
nasopharyngitis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	11 / 193 (5.70%)	19 / 382 (4.97%)	29 / 382 (7.59%)	26 / 384 (6.77%)	55 / 183 (30.05%)	104 / 369 (28.18%)	107 / 360 (29.72%)	112 / 362 (30.94%)	4 / 157 (2.55%)	4 / 309 (1.29%)	5 / 305 (1.64%)	2 / 313 (0.64%)
occurrences all number	12	22	29	31	124	196	239	222	4	4	5	2
pharyngitis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	1 / 193 (0.52%)	2 / 382 (0.52%)	7 / 382 (1.83%)	0 / 384 (0.00%)	4 / 183 (2.19%)	20 / 369 (5.42%)	17 / 360 (4.72%)	21 / 362 (5.80%)	0 / 157 (0.00%)	0 / 309 (0.00%)	0 / 305 (0.00%)	1 / 313 (0.32%)
occurrences all number	1	2	7	0	6	26	20	23	0	0	0	1
sinusitis
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	2 / 193 (1.04%)	1 / 382 (0.26%)	1 / 382 (0.26%)	4 / 384 (1.04%)	16 / 183 (8.74%)	10 / 369 (2.71%)	28 / 360 (7.78%)	27 / 362 (7.46%)	0 / 157 (0.00%)	1 / 309 (0.32%)	1 / 305 (0.33%)	1 / 313 (0.32%)
occurrences all number	2	1	1	4	22	11	41	47	0	1	1	1
upper respiratory tract infection
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	5 / 193 (2.59%)	8 / 382 (2.09%)	8 / 382 (2.09%)	8 / 384 (2.08%)	21 / 183 (11.48%)	33 / 369 (8.94%)	48 / 360 (13.33%)	42 / 362 (11.60%)	0 / 157 (0.00%)	1 / 309 (0.32%)	1 / 305 (0.33%)	2 / 313 (0.64%)
occurrences all number	5	8	8	8	27	58	67	68	0	2	1	2
urinary tract infection
alternative dictionary used: MedDRA 22.0
subjects affected / exposed	0 / 193 (0.00%)	3 / 382 (0.79%)	5 / 382 (1.31%)	5 / 384 (1.30%)	6 / 183 (3.28%)	18 / 369 (4.88%)	21 / 360 (5.83%)	21 / 362 (5.80%)	0 / 157 (0.00%)	1 / 309 (0.32%)	3 / 305 (0.98%)	0 / 313 (0.00%)
occurrences all number	0	3	5	5	9	26	25	39	0	1	3	0
vulvovaginal mycotic infection
alternative dictionary used: MedDRA 22.0
subjects affected / exposed ^[15]	1 / 56 (1.79%)	1 / 113 (0.88%)	1 / 128 (0.78%)	1 / 130 (0.77%)	2 / 54 (3.70%)	2 / 109 (1.83%)	6 / 119 (5.04%)	4 / 121 (3.31%)	0 / 49 (0.00%)	0 / 92 (0.00%)	1 / 100 (1.00%)	0 / 104 (0.00%)
occurrences all number	1	1	1	1	3	3	13	5	0	0	1	0

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

More information

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Were there any global substantial amendments to the protocol? Yes

15 Mar 2012

Changes to protocol (a): -Included monthly urine pregnancy testing for women of childbearing potential. -Removed evaluation of joint pain as a secondary objective. -Clarified use of concomitant topical products in the enrollment criteria. -Defined protocol criteria for premedication -Revised the primary analyses for categorical efficacy outcomes to a Cochran-Mantel-Haenszel (CMH) test stratified by center. -Used an MMRM approach for the primary analysis of continuous variables. -Added new details to more clearly define participants with moderate-to-severe heart failure and specified that these participants are excluded. -Revised an enrollment criterion to exclude participants positive for hepatitis B surface antigen or core antibody, regardless of their anti-hepatitis B surface antibody status. -Added a new exclusion and discontinuation criteria to exclude participants who have a condition/contradiction as addressed in local labeling for etanercept. -Revised the hepatic discontinuation rules. -Added a discontinuation rule for participants who develop symptoms suggestive of lupus-like syndrome and are positive for antibodies against double-stranded DNA. -Corrected treatment window for missed doses.

05 Nov 2012

Changes to protocol (b): -Non-inferiority analysis will be reported on both sPGA (0,1) and PASI 75 at Week 12 (non-responder imputation [NRI]) using a fixed margin approach. -The non-inferiority analysis will also be conducted using a US-only population. - The sPGA (0,1) and PASI 75 for the assessment of non-inferiority and superiority of ixekizumab to etanercept have been reordered. - The effect of center on the co-primary endpoints, sPGA (0,1) and PASI 75, will also be investigated based on the actual centers. - Additional details were added regarding the MMRM analysis. - Modified exclusion criterion to allow enrollment of participants who have had previous infection with hepatitis B virus (HBV) with conditions. - Added discontinuation requirement for positive HBV DNA test results. - Updated Study Schedule for hepatitis B monitoring. - Corrected inclusion criterion to require use of spermicide in conjunction with a diaphragm. - Clarified exclusion criterion to more clearly define participants with serious cardiac conditions - Clarified description of appropriate premedication. - Clarified the requirements for rescreening participants for tuberculosis. - Removed DNA collection at Week 24. -PASI 75 assumption for etanercept at Week 12 updated to 53%.

27 Feb 2015

Changes to protocol (c): -Modified major secondary objective for Itch to assess the proportion of participants achieving an Itch NRS ≥4 point reduction from baseline for participants who had baseline Itch NRS ≥4. -Added language to allow dosing to be increased to 80 mg ixekizumab Q2W after Week 60 during the Long-Term Extension Period (Period 3). -Modified discontinuation criteria. -Modified permitted concomitant medications. -Added language regarding collection of data on cerebrocardiovascular events for adjudication. -Updated hepatic discontinuation criteria. -Updated protocol-specified liver test criteria.

28 Mar 2017

Changes to protocol (d): -Added Crohn’s disease and ulcerative colitis adjudication. -Added clarity on dosing windows for Long-Term Extension Period.

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Clinical Trial Results: A 12-Week Multicenter, Randomized, Double-Blind, Placebo Controlled Study Comparing the Efficacy and Safety of LY2439821 to Etanercept and Placebo in Patients with Moderate to Severe Plaque Psoriasis with a Long-Term Extension Period

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of participants achieving a static Physician Global Assessment (sPGA) of (0, 1) (Efficacy of ixekizumab in participants with moderate to severe chronic plaque psoriasis. Measure: sPGA)

Primary: Number of participants achieving a static Physician Global Assessment (sPGA) of (0, 1) (Efficacy of ixekizumab in participants with moderate to severe chronic plaque psoriasis. Measure: sPGA)

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

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

Secondary: Number of participants achieving an sPGA (0) (Efficacy of ixekizumab in participants with moderate to severe chronic plaque psoriasis. Measure: sPGA)

Secondary: Number of participants achieving an sPGA (0) (Efficacy of ixekizumab in participants with moderate to severe chronic plaque psoriasis. Measure: sPGA)

Secondary: Number of Participants Achieving ≥90% (PASI 90) Improvement (Efficacy of ixekizumab in participants with moderate to severe chronic plaque psoriasis. Measure: PASI)

Secondary: Number of Participants Achieving ≥90% (PASI 90) Improvement (Efficacy of ixekizumab in participants with moderate to severe chronic plaque psoriasis. Measure: PASI)

Secondary: Number of Participants Achieving 100% (PASI 100) Improvement (Efficacy of ixekizumab in participants with moderate to severe chronic plaque psoriasis. Measure: PASI)

Secondary: Number of Participants Achieving 100% (PASI 100) Improvement (Efficacy of ixekizumab in participants with moderate to severe chronic plaque psoriasis. Measure: PASI)

Secondary: Number of Participants Achieving an Itch Numeric Rating Scale (NRS) ≥4 Point Reduction [Quality of Life and Outcome Assessments. Measures: Patient Reported Outcomes (PRO)]

Secondary: Number of Participants Achieving an Itch Numeric Rating Scale (NRS) ≥4 Point Reduction [Quality of Life and Outcome Assessments. Measures: Patient Reported Outcomes (PRO)]

Secondary: Change from Baseline in Dermatology Life Quality Index (DLQI) Total Score

Secondary: Change from Baseline in Dermatology Life Quality Index (DLQI) Total Score

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

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

Secondary: Percent of Body Surface Area (BSA) Involvement of Psoriasis

Secondary: Percent of Body Surface Area (BSA) Involvement of Psoriasis

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

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

Secondary: Change from Baseline in Quick Inventory of Depressive Symptomatology-Self Report 16 Items (QIDS-SR16) Total Score [Quality of Life and Outcome Assessments. Measures: Patient Reported Outcomes (PRO)]

Secondary: Change from Baseline in Quick Inventory of Depressive Symptomatology-Self Report 16 Items (QIDS-SR16) Total Score [Quality of Life and Outcome Assessments. Measures: Patient Reported Outcomes (PRO)]

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

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

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: Number of Participants Achieving Palmoplantar PASI ≥50% (PPASI 50) Improvement

Secondary: Number of Participants Achieving Palmoplantar PASI ≥50% (PPASI 50) Improvement

Secondary: Number of Participants Achieving Palmoplantar PASI of ≥75% (PPASI 75) Improvement

Secondary: Number of Participants Achieving Palmoplantar PASI of ≥75% (PPASI 75) Improvement

Secondary: Number of Participants Achieving Palmoplantar PASI of 100% (PPASI 100) Improvement

Secondary: Number of Participants Achieving Palmoplantar PASI of 100% (PPASI 100) Improvement

Secondary: Number of Participants With Treatment-Emergent Anti-Ixekizumab Antibodies

Secondary: Number of Participants With Treatment-Emergent Anti-Ixekizumab Antibodies

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

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

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

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

Secondary: Change From Baseline in Presenteeism of WPAI-PSO

Secondary: Change From Baseline in Presenteeism of WPAI-PSO

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

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

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A 12-Week Multicenter, Randomized, Double-Blind, Placebo Controlled Study Comparing the Efficacy and Safety of LY2439821 to Etanercept and Placebo in Patients with Moderate to Severe Plaque Psoriasis with a Long-Term Extension Period