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Clinical Trial Results:
A Phase 3 Study to Evaluate the Efficacy, Safety, and Effect of Withdrawal and Retreatment With Brodalumab in Subjects With Moderate to Severe Plaque Psoriasis: AMAGINE-1

Summary
EudraCT number	2012-000651-13
Trial protocol	PL DE
Global end of trial date	02 Oct 2015

Results information
Results version number	v1(current)
This version publication date	16 Oct 2016
First version publication date	16 Oct 2016
Other versions

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

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Trial information

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Sponsor protocol code

20120102

ISRCTN number

US NCT number

NCT01708590

WHO universal trial number (UTN)

Sponsor organisation name

Amgen, Inc.

Sponsor organisation address

One Amgen Center Drive, Thousand Oaks, CA, United States, 91320

Public contact

IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com

Scientific contact

IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com

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

02 Oct 2015

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

02 Oct 2015

Was the trial ended prematurely?

Yes

Main objective of the trial

The primary and secondary objectives of this study were to evaluate the efficacy of brodalumab compared to placebo on measures of psoriasis at weeks 12 and 52.

Protection of trial subjects

This study was conducted in accordance with applicable country, Food and Drug Administration, and International Council for Harmonisation (ICH) Good Clinical Practice (GCP) regulations/guidelines. All subjects provided written informed consent before undergoing any study-related procedures, including screening procedures. The study protocol, amendments, and the informed consent form (ICF) were reviewed by the Institutional Review Boards (IRBs) and Independent Ethics Committees (IECs). No subjects were recruited into the study and no investigational product (IP) was shipped until the IRB/IEC gave written approval of the protocol and ICF and Amgen received copies of these approvals.

Background therapy

Evidence for comparator

Actual start date of recruitment

29 Aug 2012

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

France: 36

Country: Number of subjects enrolled

Canada: 144

Country: Number of subjects enrolled

Germany: 61

Country: Number of subjects enrolled

Poland: 135

Country: Number of subjects enrolled

Switzerland: 24

Country: Number of subjects enrolled

United States: 261

Worldwide total number of subjects

661

EEA total number of subjects

232

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)

607

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

This study was conducted at 73 centers in Europe, Canada, and the United States. Participants were enrolled from 29 August 2012 until 8 March 2013.

Screening details

Eligible subjects were men and women from 18 to 75 years of age with stable moderate to severe plaque psoriasis diagnosed at least 6 months before the first dose of investigational product (eg, no morphology changes or significant flares of disease activity in the opinion of the investigator).

Period 1 title

Induction Phase (Weeks 1-12)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Data analyst

Blinding implementation details

Subjects were randomized at baseline via an interactive voice response system (IVRS) to receive 210 mg brodalumab, 140 mg brodalumab, or placebo in a 1:1:1 ratio stratified by baseline total body weight (≤ 100 kg; > 100 kg), by prior biologic use (subjects with prior biologic use were capped at 50% of the study population), and by geographic region (defined by country for non-US countries and by geographic region in the US [US-West, US-Midwest, US-Northeast, US-South]).

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants received placebo matching brodalumab administered via subcutaneous injection on day 1 and at weeks 1, 2, 4, 6, 8, and 10.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection on day 1 and at weeks 1, 2, 4, 6, 8, and 10.

Brodalumab 140 mg

Arm description

Participants received 140 mg brodalumab via subcutaneous injection on day 1 and at weeks 1, 2, 4, 6, 8, and 10.

Arm type

Experimental

Investigational medicinal product name

Brodalumab

Investigational medicinal product code

AMG 827

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection on day 1 and at weeks 1, 2, 4, 6, 8, and 10.

Brodalumab 210 mg

Arm description

Participants received 210 mg brodalumab via subcutaneous injection on day 1 and at weeks 1, 2, 4, 6, 8, and 10.

Arm type

Experimental

Investigational medicinal product name

Brodalumab

Investigational medicinal product code

AMG 827

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection on day 1 and at weeks 1, 2, 4, 6, 8, and 10.

Number of subjects in period 1	Placebo	Brodalumab 140 mg	Brodalumab 210 mg
Started	220	219	222
Completed	208	208	212
Not completed	12	11	10
Consent withdrawn by subject	3	3	4
Administrative decision	-	-	1
Other	-	2	-
Adverse event	3	3	2
Ineligibility determined	2	-	-
Lost to follow-up	1	1	1
Protocol deviation	2	1	2
Requirement for alternative therapy	1	-	-
Noncompliance	-	1	-

Period 2 title

Withdrawal Phase (Weeks 12 - 52)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Data analyst

Blinding implementation details

Subjects originally randomized to either of the brodalumab arms and who had an sPGA = 0 or 1 at week 12 were re-randomized at week 12 to receive brodalumab at their originally randomized dose or placebo in a 1:1 ratio, stratified by week 12 total body weight (≤ 100 kg vs > 100 kg) and the subject's week 12 response (sPGA = 0 vs sPGA = 1). Subjects originally randomized to the placebo arm and any subjects who did not meet the criteria for re-randomization received 210 mg Q2W brodalumab.

Are arms mutually exclusive

Yes

Non-rerandomized Subjects

Arm description

Participants who received placebo in the Induction Phase or who did not have an sPGA = 0 or 1 at the week 12 visit received 210 mg brodalumab every 2 weeks (Q2W) from week 12 in the Withdrawal Phase.

Arm type

Experimental

Investigational medicinal product name

Brodalumab

Investigational medicinal product code

AMG 827

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection Q2W.

Brodalumab 140 mg / Placebo

Arm description

Participants who received 140 mg Q2W brodalumab in the Induction Phase who were re-randomized to receive placebo from week 12 in the Withdrawal phase.

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection every 2 weeks.

Brodalumab 140 mg / Brodalumab 140 mg

Arm description

Participants who received 140 mg Q2W brodalumab in the Induction Phase who were re-randomized to receive 140 mg brodalumab from week 12 in the Withdrawal phase.

Arm type

Experimental

Investigational medicinal product name

Brodalumab

Investigational medicinal product code

AMG 827

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection Q2W.

Brodalumab 210 mg / Placebo

Arm description

Participants who received 210 mg Q2W brodalumab in the Induction Phase who were re-randomized to receive placebo from week 12 in the Withdrawal Phase.

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection every 2 weeks.

Brodalumab 210 mg / Brodalumab 210 mg

Arm description

Participants who received 210 mg Q2W brodalumab in the Induction Phase who were re-randomized to receive 210 mg brodalumab Q2W from week 12 in the Withdrawal Phase.

Arm type

Experimental

Investigational medicinal product name

Brodalumab

Investigational medicinal product code

AMG 827

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection Q2W.

Number of subjects in period 2	Non-rerandomized Subjects	Brodalumab 140 mg / Placebo	Brodalumab 140 mg / Brodalumab 140 mg	Brodalumab 210 mg / Placebo	Brodalumab 210 mg / Brodalumab 210 mg
Started	345	59	57	84	83
Received Study Drug	344	59	57	84	83
Completed	290	6	45	2	74
Not completed	55	53	12	82	9
Consent withdrawn by subject	11	-	-	1	-
Administrative decision	5	-	-	1	-
entered retreatment phase	-	53	12	79	5
Other	10	-	-	-	-
Death	2	-	-	-	1
Adverse event	7	-	-	-	2
Ineligibility determined	1	-	-	-	-
Lost to follow-up	3	-	-	1	1
Requirement for alternative therapy	16	-	-	-	-

Period 3 title

Retreatment Phase (week 16-52)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Data analyst

Blinding implementation details

Participants who re-randomized at week 12 qualified for retreatment upon return of disease (defined as an sPGA ≥ 3) at or after week 16 and through week 52.

Are arms mutually exclusive

Yes

Brodalumab 140 mg / Placebo / Brodalumab 140 mg

Arm description

Participants who received 140 mg Q2W brodalumab in the Induction Phase who were re-randomized to receive placebo from week 12 in the Withdrawal Phase and then received 140 mg brodalumab in the Retreatment Phase.

Arm type

Experimental

Investigational medicinal product name

Brodalumab

Investigational medicinal product code

AMG 827

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection Q2W.

Brodalumab 140 mg / Brodalumab 140 mg /Brodalumab 140 mg

Arm description

Participants who received 140 mg Q2W brodalumab in the Induction Phase who were re-randomized to receive 140 mg brodalumab from week 12 in the Withdrawal phase and continued to receive 140 mg brodalumab in the Retreatment Phase.

Arm type

Experimental

Investigational medicinal product name

Brodalumab

Investigational medicinal product code

AMG 827

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection Q2W.

Brodalumab 210 mg / Placebo / Brodalumab 210 mg

Arm description

Participants who received 210 mg brodalumab Q2W in the Induction Phase who were re-randomized to receive placebo from week 12 in the Withdrawal Phase and then received 210 mg brodalumab Q2W in the Retreatment Phase.

Arm type

Experimental

Investigational medicinal product name

Brodalumab

Investigational medicinal product code

AMG 827

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection Q2W.

Brodalumab 210 mg / Brodalumab 210 mg / Brodalumab 210 mg

Arm description

Participants who received 210 mg Q2W brodalumab in the Induction Phase who were re-randomized to receive 210 mg brodalumab Q2W from week 12 in the Withdrawal Phase.

Arm type

Experimental

Investigational medicinal product name

Brodalumab

Investigational medicinal product code

AMG 827

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection Q2W.

Number of subjects in period 3 ^[1]	Brodalumab 140 mg / Placebo / Brodalumab 140 mg	Brodalumab 140 mg / Brodalumab 140 mg /Brodalumab 140 mg	Brodalumab 210 mg / Placebo / Brodalumab 210 mg	Brodalumab 210 mg / Brodalumab 210 mg / Brodalumab 210 mg
Started	53	12	79	5
Completed	35	4	66	2
Not completed	18	8	13	3
Consent withdrawn by subject	-	1	1	1
Entered rescue phase prior to week 52	17	7	10	2
Death	-	-	1	-
Adverse event	-	-	1	-
Lost to follow-up	1	-	-	-

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Only participants who qualified for retreatment upon return of disease (defined as an sPGA ≥ 3) at or after week 16 and through week 52 entered the Retreatment Phase.

Baseline characteristics

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Reporting group title

Placebo

Reporting group description

Participants received placebo matching brodalumab administered via subcutaneous injection on day 1 and at weeks 1, 2, 4, 6, 8, and 10.

Reporting group title

Brodalumab 140 mg

Reporting group description

Participants received 140 mg brodalumab via subcutaneous injection on day 1 and at weeks 1, 2, 4, 6, 8, and 10.

Reporting group title

Brodalumab 210 mg

Reporting group description

Participants received 210 mg brodalumab via subcutaneous injection on day 1 and at weeks 1, 2, 4, 6, 8, and 10.

Reporting group values	Placebo	Brodalumab 140 mg	Brodalumab 210 mg	Total
Number of subjects	220	219	222	661
Age Categorical
Units: Subjects
< 65 years	202	199	206	607
≥ 65 years	18	20	16	54
Age Continuous
Units: years
arithmetic mean (standard deviation)	46.9 ( 13.2 )	45.8 ( 13.4 )	46.3 ( 12.2 )	-
Gender Categorical
Units: Subjects
Female	59	57	61	177
Male	161	162	161	484
Race
Units: Subjects
American Indian or Alaska Native	0	1	1	2
Asian	8	10	10	28
Black (or African American)	6	8	3	17
Native Hawaiian/Other Pacific Islander	2	1	2	5
White	202	196	203	601
Other	2	3	3	8
Weight
Units: Subjects
≤ 100 kg	159	156	156	471
> 100 kg	61	63	66	190
Prior Biologic Use
Units: Subjects
Yes	101	99	105	305
No	119	120	117	356
Region
Units: Subjects
Canada	47	49	48	144
France	12	10	14	36
Germany	20	20	21	61
Poland	45	45	45	135
Switzerland	8	9	7	24
United States-Midwest	10	9	10	29
United States-Northeast	10	10	12	32
United States-South	20	19	17	56
United States-West	48	48	48	144
Static Physician Global Assessment of Psoriasis (sPGA)
The sPGA is a 6-point scale ranging from 0 (clear) to 5 (very severe) used to measure the severity of disease (induration, scaling, and erythema).
Units: Subjects
Clear	0	0	0	0
Almost Clear	0	0	0	0
Mild	0	0	0	0
Moderate	114	129	121	364
Severe	91	80	87	258
Very Severe	15	10	14	39
Duration of Psoriasis
Units: years
arithmetic mean (standard deviation)	20.7 ( 12.1 )	19.4 ( 12.5 )	20.4 ( 13.2 )	-
Psoriasis Area and Severity Index (PASI) Score
The PASI measures the average redness (erythema), thickness (induration), and scaliness (each graded on a 0 to 4 scale) of psoriasis lesions, weighted by the area of involvement. The total PASI score ranges from 0 to 72. The higher the total score, the more severe the disease.
Units: units on a scale
arithmetic mean (standard deviation)	19.72 ( 7.71 )	19.95 ( 7.41 )	19.41 ( 6.61 )	-
Psoriasis Body Surface Area (BSA) Involvement
Units: percent
arithmetic mean (standard deviation)	26.9 ( 17.11 )	27.42 ( 17.1 )	25.06 ( 15.25 )	-
Psoriasis Scalp Severity Index (PSSI)
The Psoriasis Scalp Severity Index (PSSI) measures the extent of psoriasis involvement and the severity of erythema, infiltration, and desquamation of the scalp. Involvement and severity of psoriasis for the PSSI is scored by physicians using a scale from 0 to 72, where 0 = no psoriasis, and higher scores indicating more severe disease. The PSSI calculation does not include the face or neck area. Data were available for 219, 219 and 222 subjects in each group respectively.
Units: units on a scale
arithmetic mean (standard deviation)	19.97 ( 14.57 )	19.67 ( 13.72 )	16.71 ( 13.48 )	-
Psoriasis Scalp Surface Area (SSA) Involvement
Data are available for 219, 219 and 222 subjects in each group respectively.
Units: percent
arithmetic mean (standard deviation)	32.42 ( 28.64 )	34.6 ( 29.24 )	28.68 ( 27.53 )	-
Nail Psoriasis Severity Index (NAPSI)
The NAPSI scale is an objective, numeric, and reproducible grading system for nail psoriasis that incorporates the many different features of nail psoriasis. Each quarter of the nail was scored for the presence (1) or absence (0) of 8 clinical features for a score of 0-4 for each feature. The total score for each nail ranges from 0 (absent) to 32 (worst). Data are reported for the worst nail for subjects with baseline nail involvement; 59, 66 and 62 subjects in each treatment group respectively.
Units: units on a scale
arithmetic mean (standard deviation)	9.54 ( 3.78 )	9.26 ( 4.02 )	9.16 ( 3.99 )	-
Dermatology Life Quality Index (DLQI)
The DLQI is a skin disease-specific instrument to evaluate health-related quality of life. Participants evaluate the degree that psoriasis has affected their quality of life in the last week, including symptoms and feelings, daily and leisure activities, work or school activities, personal relationships and treatment related feelings. Participants answer 10 questions on a scale from 0 (not at all) to 3 (very much); the total score ranges from 0 (best possible score) to 30 (worst possible score). Data are available for 217, 216, and 221 participants in each treatment group respectively.
Units: units on a scale
arithmetic mean (standard deviation)	13.9 ( 6.8 )	14.3 ( 7.5 )	14.2 ( 7.3 )	-
EuroQol-5D (EQ-5D)
The EQ-5D captures 2 types of information, a descriptive profile, or health state, and an overall health rating using a visual analog scale. The health states include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, answered as 1 (no problem), 2 (some problem), or 3 (major problem). A weighted index score is calculated by applying coefficients from a validated value set and ranges from -0.594 to 1, with -0.594 representing death and 1 representing the perfect health state. Data are available for 216, 216 and 221 participants in each treatment group respectively.
Units: units on a scale
arithmetic mean (standard deviation)	0.62 ( 0.29 )	0.61 ( 0.32 )	0.6 ( 0.32 )	-
Hospital Anxiety and Depression Scale (HADS) Anxiety Score
The HADS is a 14-item questionnaire assessing subject’s symptoms of depression and anxiety. The measure consists of 7 items reflecting anxiety and 7 items reflecting depression. Each item can be answered by the patient on a 4-point (0–3) response category so the possible scores ranged from 0 to 21 for anxiety and 0 to 21 for depression. Data are available for 216, 216 and 221 participants in each treatment group respectively.
Units: units on a scale
arithmetic mean (standard deviation)	6.42 ( 3.81 )	6.59 ( 4.2 )	6.68 ( 4.28 )	-
HADS Depression Score
The HADS is a 14-item questionnaire assessing subject’s symptoms of depression and anxiety. The measure consists of 7 items reflecting anxiety and 7 items reflecting depression. Each item can be answered by the patient on a 4-point (0–3) response category so the possible scores ranged from 0 to 21 for anxiety and 0 to 21 for depression. Data are available for 216, 216 and 221 participants in each treatment group respectively.
Units: units on a scale
arithmetic mean (standard deviation)	5.28 ( 3.92 )	5.18 ( 4.11 )	5.47 ( 4.17 )	-
Medical Outcomes Short Form-36 (SF-36) Physical Component Score
The SF-36 assesses the general quality of life by evaluating the domains of physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. The questionnaire consists of 36 questions that are completed by the participant.. The individual domain scores are aggregated to derive a physical-component summary score and a mental-component summary score which range from 0 to 100, with higher scores indicating a better level of functioning. Data are available for 216, 216 and 221 participants in each treatment group respectively.
Units: units on a scale
arithmetic mean (standard deviation)	46.73 ( 9.44 )	47.7 ( 9.24 )	46.99 ( 9.25 )	-
SF-36 Mental Component Score
The SF-36 assesses the general quality of life by evaluating the domains of physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. The questionnaire consists of 36 questions that are completed by the participant.. The individual domain scores are aggregated to derive a physical-component summary score and a mental-component summary score which range from 0 to 100, with higher scores indicating a better level of functioning. Data are available for 216, 216 and 221 participants in each treatment group respectively.
Units: units on a scale
arithmetic mean (standard deviation)	45.98 ( 11.23 )	45.3 ( 11.22 )	45.48 ( 11.65 )	-
Psoriasis Symptom Inventory Total Score Weekly Average
The Psoriasis Symptom Inventory consists of eight psoriasis-specific items. Participants rated the severity of their symptoms in the last 24 hours on a scale from ‘not at all’ (0) to ‘very severe’ (4) in an electronic diary once a day. Total scores range from 0 to 32 with higher scores indicating worse symptoms. The daily assessment of the Psoriasis Symptom Inventory was analyzed as a weekly average. Data are available for 211, 210 and 209 participants in each treatment group respectively.
Units: units on a scale
arithmetic mean (standard deviation)	19 ( 6.7 )	19.7 ( 7.3 )	18.9 ( 6.7 )	-

End points

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Reporting group title

Placebo

Reporting group description

Participants received placebo matching brodalumab administered via subcutaneous injection on day 1 and at weeks 1, 2, 4, 6, 8, and 10.

Reporting group title

Brodalumab 140 mg

Reporting group description

Participants received 140 mg brodalumab via subcutaneous injection on day 1 and at weeks 1, 2, 4, 6, 8, and 10.

Reporting group title

Brodalumab 210 mg

Reporting group description

Participants received 210 mg brodalumab via subcutaneous injection on day 1 and at weeks 1, 2, 4, 6, 8, and 10.

Reporting group title

Non-rerandomized Subjects

Reporting group description

Participants who received placebo in the Induction Phase or who did not have an sPGA = 0 or 1 at the week 12 visit received 210 mg brodalumab every 2 weeks (Q2W) from week 12 in the Withdrawal Phase.

Reporting group title

Brodalumab 140 mg / Placebo

Reporting group description

Participants who received 140 mg Q2W brodalumab in the Induction Phase who were re-randomized to receive placebo from week 12 in the Withdrawal phase.

Reporting group title

Brodalumab 140 mg / Brodalumab 140 mg

Reporting group description

Participants who received 140 mg Q2W brodalumab in the Induction Phase who were re-randomized to receive 140 mg brodalumab from week 12 in the Withdrawal phase.

Reporting group title

Brodalumab 210 mg / Placebo

Reporting group description

Participants who received 210 mg Q2W brodalumab in the Induction Phase who were re-randomized to receive placebo from week 12 in the Withdrawal Phase.

Reporting group title

Brodalumab 210 mg / Brodalumab 210 mg

Reporting group description

Participants who received 210 mg Q2W brodalumab in the Induction Phase who were re-randomized to receive 210 mg brodalumab Q2W from week 12 in the Withdrawal Phase.

Reporting group title

Brodalumab 140 mg / Placebo / Brodalumab 140 mg

Reporting group description

Reporting group title

Brodalumab 140 mg / Brodalumab 140 mg /Brodalumab 140 mg

Reporting group description

Reporting group title

Brodalumab 210 mg / Placebo / Brodalumab 210 mg

Reporting group description

Reporting group title

Brodalumab 210 mg / Brodalumab 210 mg / Brodalumab 210 mg

Reporting group description

Participants who received 210 mg Q2W brodalumab in the Induction Phase who were re-randomized to receive 210 mg brodalumab Q2W from week 12 in the Withdrawal Phase.

Primary: Percentage of Participants with a 75% or Greater Improvement from Baseline in Psoriasis Area and Severity Index (PASI 75) at Week 12

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End point title

Percentage of Participants with a 75% or Greater Improvement from Baseline in Psoriasis Area and Severity Index (PASI 75) at Week 12

End point description

End point type

Primary

End point timeframe

Baseline and week 12

End point values	Placebo	Brodalumab 140 mg	Brodalumab 210 mg
Number of subjects analysed	220	219	222
Units: percentage of participants
number (confidence interval 95%)	2.7 (1 to 5.8)	60.3 (53.5 to 66.8)	83.3 (77.8 to 88)

Difference in Response Rates

Comparison groups

Brodalumab 210 mg v Placebo

Number of subjects included in analysis

442

Analysis specification

Pre-specified

Analysis type

superiority ^[1]

P-value

< 0.001 ^[2]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[1] - To maintain the family-wise type-1 error rate for all co-primary and key secondary endpoints at 5% 2-sided, a sequential testing approach was followed. Reported p-values were adjusted for multiplicity.
[2] - CMH test adjusted for baseline weight (≤ 100 kg, > 100 kg), prior biologic use (yes, no), and geographic region (US, Canada, outside North America) and baseline PASI score (≤ median, > median).

Difference in Response Rates

Comparison groups

Brodalumab 140 mg v Placebo

Number of subjects included in analysis

439

Analysis specification

Pre-specified

Analysis type

superiority ^[3]

P-value

< 0.001 ^[4]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[3] - To maintain the family-wise type-1 error rate for all co-primary and key secondary endpoints at 5% 2-sided, a sequential testing approach was followed. Reported p-values were adjusted for multiplicity.
[4] - CMH test adjusted for baseline weight (≤ 100 kg, > 100 kg), prior biologic use (yes, no), and geographic region (US, Canada, outside North America) and baseline PASI score (≤ median, > median).

Primary: Percentage of Participants with a Static Physician’s Global Assessment (sPGA) of Clear or Almost Clear at Week 12

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End point title

Percentage of Participants with a Static Physician’s Global Assessment (sPGA) of Clear or Almost Clear at Week 12

End point description

End point type

Primary

End point timeframe

Week 12

End point values	Placebo	Brodalumab 140 mg	Brodalumab 210 mg
Number of subjects analysed	220	219	222
Units: percentage of participants
number (confidence interval 95%)	1.4 (0.3 to 3.9)	53.9 (47 to 60.6)	75.7 (69.5 to 81.2)

Difference in Response Rates

Comparison groups

Brodalumab 210 mg v Placebo

Number of subjects included in analysis

442

Analysis specification

Pre-specified

Analysis type

superiority ^[5]

P-value

< 0.001 ^[6]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[5] - To maintain the family-wise type-1 error rate for all co-primary and key secondary endpoints at 5% 2-sided, a sequential testing approach was followed. Reported p-values were adjusted for multiplicity.
[6] - CMH test adjusted for baseline weight (≤ 100 kg, > 100 kg), prior biologic use (yes, no), and geographic region (US, Canada, outside North America) and baseline sPGA score (3, 4, 5).

Difference in Response rates

Comparison groups

Brodalumab 140 mg v Placebo

Number of subjects included in analysis

439

Analysis specification

Pre-specified

Analysis type

superiority ^[7]

P-value

< 0.001 ^[8]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[7] - To maintain the family-wise type-1 error rate for all co-primary and key secondary endpoints at 5% 2-sided, a sequential testing approach was followed. Reported p-values were adjusted for multiplicity.
[8] - CMH test adjusted for baseline weight (≤ 100 kg, > 100 kg), prior biologic use (yes, no), and geographic region (US, Canada, outside North America) and baseline sPGA score (3, 4, 5).

Secondary: Percentage of Participants with a 100% Improvement from Baseline in PASI (PASI 100) at Week 12

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End point title

Percentage of Participants with a 100% Improvement from Baseline in PASI (PASI 100) at Week 12

End point description

End point type

Secondary

End point timeframe

Baseline and week 12

End point values	Placebo	Brodalumab 140 mg	Brodalumab 210 mg
Number of subjects analysed	220	219	222
Units: percentage of participants
number (confidence interval 95%)	0.5 (0 to 2.5)	23.3 (17.9 to 29.5)	41.9 (35.3 to 48.7)

Difference in Response Rates

Comparison groups

Brodalumab 210 mg v Placebo

Number of subjects included in analysis

442

Analysis specification

Pre-specified

Analysis type

superiority ^[9]

P-value

< 0.001 ^[10]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[9] - To maintain the family-wise type-1 error rate for all co-primary and key secondary endpoints at 5% 2-sided, a sequential testing approach was followed. Reported p-values were adjusted for multiplicity.
[10] - CMH test adjusted for baseline weight (≤ 100 kg, > 100 kg), prior biologic use (yes, no), and geographic region (US, Canada, outside North America) and baseline PASI score (≤ median, > median).

Difference in Response rates

Comparison groups

Brodalumab 140 mg v Placebo

Number of subjects included in analysis

439

Analysis specification

Pre-specified

Analysis type

superiority ^[11]

P-value

< 0.001 ^[12]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[11] - To maintain the family-wise type-1 error rate for all co-primary and key secondary endpoints at 5% 2-sided, a sequential testing approach was followed. Reported p-values were adjusted for multiplicity.
[12] - CMH test adjusted for baseline weight (≤ 100 kg, > 100 kg), prior biologic use (yes, no), and geographic region (US, Canada, outside North America) and baseline PASI score (≤ median, > median).

Secondary: Percentage of Participants with an sPGA of Clear at Week 12

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End point title

Percentage of Participants with an sPGA of Clear at Week 12

End point description

End point type

Secondary

End point timeframe

Week 12

End point values	Placebo	Brodalumab 140 mg	Brodalumab 210 mg
Number of subjects analysed	220	219	222
Units: percentage of participants
number (confidence interval 95%)	0.5 (0 to 2.5)	23.3 (17.9 to 29.5)	41.9 (35.3 to 48.7)

Difference in Response Rates

Comparison groups

Brodalumab 210 mg v Placebo

Number of subjects included in analysis

442

Analysis specification

Pre-specified

Analysis type

superiority ^[13]

P-value

< 0.001 ^[14]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[13] - To maintain the family-wise type-1 error rate for all co-primary and key secondary endpoints at 5% 2-sided, a sequential testing approach was followed. Reported p-values were adjusted for multiplicity.
[14] - CMH test adjusted for baseline weight (≤ 100 kg, > 100 kg), prior biologic use (yes, no), and geographic region (US, Canada, outside North America) and baseline sPGA score (3, 4, 5).

Difference in Response Rates

Comparison groups

Brodalumab 140 mg v Placebo

Number of subjects included in analysis

439

Analysis specification

Pre-specified

Analysis type

superiority ^[15]

P-value

< 0.001 ^[16]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[15] - To maintain the family-wise type-1 error rate for all co-primary and key secondary endpoints at 5% 2-sided, a sequential testing approach was followed. Reported p-values were adjusted for multiplicity.
[16] - CMH test adjusted for baseline weight (≤ 100 kg, > 100 kg), prior biologic use (yes, no), and geographic region (US, Canada, outside North America) and baseline sPGA score (3, 4, 5).

Secondary: Percentage of Rerandomized Participants with an sPGA of Clear or Almost Clear at Week 52

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End point title

Percentage of Rerandomized Participants with an sPGA of Clear or Almost Clear at Week 52

End point description

Physician’s global assessment of the subject’s psoriasis based on the severity of induration, scaling, and erythema assessed on a 6-point scale ranging from 0 (clear) to 5 (very severe). A sPGA response is defined as a sPGA value of clear (score 0) or almost clear (score 1). This endpoint was analyzed in subjects rerandomized into the withdrawal phase. Non-responder imputation (NRI) was used to impute missing data; subjects who experienced return of disease through week 52 were imputed as non-responders at the time of qualification.

End point type

Secondary

End point timeframe

Week 52

End point values	Brodalumab 140 mg / Placebo	Brodalumab 140 mg / Brodalumab 140 mg	Brodalumab 210 mg / Placebo	Brodalumab 210 mg / Brodalumab 210 mg
Number of subjects analysed	59	57	84	83
Units: percentage of participants
number (confidence interval 95%)	5.1 (1.1 to 14.1)	70.2 (56.6 to 81.6)	0 (0 to 4.3)	83.1 (73.3 to 90.5)

Difference in Response Rates

Comparison groups

Brodalumab 210 mg / Brodalumab 210 mg v Brodalumab 210 mg / Placebo

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority ^[17]

P-value

< 0.001 ^[18]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[17] - To maintain the family-wise type-1 error rate for all co-primary and key secondary endpoints at 5% 2-sided, a sequential testing approach was followed. Reported p-values were adjusted for multiplicity.
[18] - CMH test adjusted for week 12 total body weight (≤ 100 kg, > 100 kg) and week 12 sPGA (0, ≥ 1).

Difference in Response Rates

Comparison groups

Brodalumab 140 mg / Brodalumab 140 mg v Brodalumab 140 mg / Placebo

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

superiority ^[19]

P-value

< 0.001 ^[20]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[19] - To maintain the family-wise type-1 error rate for all co-primary and key secondary endpoints at 5% 2-sided, a sequential testing approach was followed. Reported p-values were adjusted for multiplicity.
[20] - CMH test adjusted for week 12 total body weight (≤ 100 kg, > 100 kg) and week 12 sPGA (0, ≥ 1).

Secondary: Percentage of Participants with a Psoriasis Symptom Inventory (PSI) Response at Week 12

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End point title

Percentage of Participants with a Psoriasis Symptom Inventory (PSI) Response at Week 12

End point description

The Psoriasis Symptom Inventory consists of eight psoriasis-specific items. Participants rated the severity of their symptoms in the last 24 hours on a scale from ‘not at all’ (0) to ‘very severe’ (4) in an electronic diary once a day. Total scores range from 0 to 32 with higher scores indicating worse symptoms. The daily assessment of the Psoriasis Symptom Inventory was analyzed as a weekly average. A PSI response is defined a total score ≤ 8 with no item scores > 1. Non-responder imputation was used to impute missing data.

End point type

Secondary

End point timeframe

Week 12

End point values	Placebo	Brodalumab 140 mg	Brodalumab 210 mg
Number of subjects analysed	220	219	222
Units: percentage of participants
number (confidence interval 95%)	4.1 (1.9 to 7.6)	53 (46.1 to 59.7)	60.8 (54.1 to 67.3)

Difference in Response Rate

Comparison groups

Brodalumab 210 mg v Placebo

Number of subjects included in analysis

442

Analysis specification

Pre-specified

Analysis type

superiority ^[21]

P-value

< 0.001 ^[22]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[21] - To maintain the family-wise type-1 error rate for all co-primary and key secondary endpoints at 5% 2-sided, a sequential testing approach was followed. Reported p-values were adjusted for multiplicity.
[22] - CMH test adjusted for baseline weight (≤ 100 kg, > 100 kg), prior biologic use (yes, no), and geographic region (US, Canada, outside North America) and baseline PSI score (≤ median, > median).

Difference in Response Rate

Comparison groups

Brodalumab 140 mg v Placebo

Number of subjects included in analysis

439

Analysis specification

Pre-specified

Analysis type

superiority ^[23]

P-value

< 0.001 ^[24]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[23] - To maintain the family-wise type-1 error rate for all co-primary and key secondary endpoints at 5% 2-sided, a sequential testing approach was followed. Reported p-values were adjusted for multiplicity.
[24] - CMH test adjusted for baseline weight (≤ 100 kg, > 100 kg), prior biologic use (yes, no), and geographic region (US, Canada, outside North America) and baseline PSI score (≤ median, > median).

Secondary: Time to sPGA Response During the Induction Phase

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End point title

Time to sPGA Response During the Induction Phase

End point description

Time to sPGA response is calculated from the first dose of study drug to the assessment day of first sPGA response. Response is an sPGA score of 0 (clear) or 1 (almost clear). Time to sPGA response was analyzed using Kaplan-Meier methods. Subjects who discontinued prior to the study day 91 assessment and subjects who reached the study day 91 without achieving response were censored at the date of their last assessment. "99999" indicates data not estimable due to the low number of events.

End point type

Secondary

End point timeframe

12 weeks

End point values	Placebo	Brodalumab 140 mg	Brodalumab 210 mg
Number of subjects analysed	220	219	222
Units: weeks
median (confidence interval 95%)	99999 (99999 to 99999)	6.14 (5.71 to 6.43)	4.29 (4.14 to 6.14)

No statistical analyses for this end point

Secondary: Time to PASI Response During the Induction Phase

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End point title

Time to PASI Response During the Induction Phase

End point description

Time to PASI 75/90/100 response is calculated as the time from first dose of study drug to assessment day of first PASI 75/90/100 response. Time to PASI response was analyzed using Kaplan-Meier methods. Subjects who discontinued prior to the study day 91 assessment and subjects who reached the study day 91 without achieving response were censored at the date of their last assessment. "99999" indicates data not estimable due to the low number of events.

End point type

Secondary

End point timeframe

12 weeks

End point values	Placebo	Brodalumab 140 mg	Brodalumab 210 mg
Number of subjects analysed	220	219	222
Units: weeks
median (confidence interval 95%)
PASI 75	99999 (99999 to 99999)	6.14 (4.57 to 6.14)	4.14 (4.14 to 4.29)
PASI 90	99999 (99999 to 99999)	10.14 (8.14 to 12.14)	6.29 (6.14 to 8.14)
PASI 100	99999 (99999 to 99999)	99999 (99999 to 99999)	12.14 (10.14 to 99999)

No statistical analyses for this end point

Secondary: Percentage of Participants with an sPGA of Clear or Almost Clear at Each Visit in the Induction Phase

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End point title

Percentage of Participants with an sPGA of Clear or Almost Clear at Each Visit in the Induction Phase

End point description

End point type

Secondary

End point timeframe

Weeks 1, 2, 4, 6, 8, and 10

End point values	Placebo	Brodalumab 140 mg	Brodalumab 210 mg
Number of subjects analysed	220	219	222
Units: percentage of participants
number (confidence interval 95%)
Week 1	0 (0 to 1.7)	2.3 (0.7 to 5.2)	5.4 (2.8 to 9.3)
Week 2	0 (0 to 1.7)	15.1 (10.6 to 20.5)	18.9 (14 to 24.7)
Week 4	0 (0 to 1.7)	40.2 (33.6 to 47)	52.7 (45.9 to 59.4)
Week 6	0 (0 to 1.7)	51.6 (44.8 to 58.4)	66.7 (60 to 72.8)
Week 8	1.8 (0.5 to 4.6)	55.3 (48.4 to 62)	74.3 (68.1 to 79.9)
Week 10	2.3 (0.7 to 5.2)	56.2 (49.3 to 62.8)	77.5 (71.4 to 82.8)

No statistical analyses for this end point

Secondary: Percentage of Participants with an sPGA of Clear at Each Visit in the Induction Phase

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End point title

Percentage of Participants with an sPGA of Clear at Each Visit in the Induction Phase

End point description

End point type

Secondary

End point timeframe

Weeks 1, 2, 4, 6, 8 and 10

End point values	Placebo	Brodalumab 140 mg	Brodalumab 210 mg
Number of subjects analysed	220	219	222
Units: percentage of participants
number (confidence interval 95%)
Week 1	0 (0 to 1.7)	0 (0 to 1.7)	0 (0 to 1.6)
Week 2	0 (0 to 1.7)	1.4 (0.3 to 4)	0.9 (0.1 to 3.2)
Week 4	0 (0 to 1.7)	7.8 (4.6 to 12.1)	10.4 (6.7 to 15.1)
Week 6	0 (0 to 1.7)	15.5 (11 to 21)	25.2 (19.7 to 31.5)
Week 8	0 (0 to 1.7)	20.1 (15 to 26)	30.6 (24.6 to 37.1)
Week 10	0.5 (0 to 2.5)	21.5 (16.2 to 27.5)	39.6 (33.2 to 46.4)

No statistical analyses for this end point

Secondary: Percentage of Participants with a PASI 75 at Each Visit in the Induction Phase

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End point title

Percentage of Participants with a PASI 75 at Each Visit in the Induction Phase

End point description

End point type

Secondary

End point timeframe

Baseline and Weeks 1, 2, 4, 6, 8, and 10

End point values	Placebo	Brodalumab 140 mg	Brodalumab 210 mg
Number of subjects analysed	220	219	222
Units: percentage of participants
number (confidence interval 95%)
Week 1	0 (0 to 1.7)	1.4 (0.3 to 4)	3.2 (1.3 to 6.4)
Week 2	0.5 (0 to 2.5)	14.6 (10.2 to 20)	23 (17.6 to 29.1)
Week 4	1.4 (0.3 to 3.9)	41.6 (35 to 48.4)	62.2 (55.4 to 68.6)
Week 6	2.3 (0.7 to 5.2)	62.1 (55.3 to 68.6)	75.7 (69.5 to 81.2)
Week 8	2.3 (0.7 to 5.2)	63.5 (56.7 to 69.9)	80.6 (74.8 to 85.6)
Week 10	3.2 (1.3 to 6.4)	62.6 (55.8 to 69)	82 (76.3 to 86.8)

No statistical analyses for this end point

Secondary: Percentage of Participants with a PASI 100 at Each Visit in the Induction Phase

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End point title

Percentage of Participants with a PASI 100 at Each Visit in the Induction Phase

End point description

End point type

Secondary

End point timeframe

Baseline and Weeks 1, 2, 4, 6, 8 and 10

End point values	Placebo	Brodalumab 140 mg	Brodalumab 210 mg
Number of subjects analysed	220	219	222
Units: percentage of participants
number (confidence interval 95%)
Week 1	0 (0 to 1.7)	0 (0 to 1.7)	0 (0 to 1.6)
Week 2	0 (0 to 1.7)	1.4 (0.3 to 4)	0.9 (0.1 to 3.2)
Week 4	0 (0 to 1.7)	7.8 (4.6 to 12.1)	10.4 (6.7 to 15.1)
Week 6	0 (0 to 1.7)	15.5 (11 to 21)	25.2 (19.7 to 31.5)
Week 8	0 (0 to 1.7)	20.1 (15 to 26)	30.6 (24.6 to 37.1)
Week 10	0.5 (0 to 2.5)	21.5 (16.2 to 27.5)	39.2 (32.7 to 45.9)

No statistical analyses for this end point

Secondary: Percentage of Participants with a PASI 50 at Each Visit in the Induction Phase

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End point title

Percentage of Participants with a PASI 50 at Each Visit in the Induction Phase

End point description

The PASI measures the average redness (erythema), thickness (induration), and scaliness (each graded on a 0 to 4 scale) of psoriasis lesions, weighted by the area of involvement in the four main body areas (i.e., head and neck, trunk, upper extremities, and lower extremities). PASI scores can range from 0.0 to 72.0, with higher scores indicating greater severity and/or more extensive psoriasis. A PASI 50% response is a 50% or greater improvement from baseline. Non-responder imputation (NRI) was used to impute missing data.

End point type

Secondary

End point timeframe

Baseline and Weeks 1, 2, 4, 6, 8, 10 and 12

End point values	Placebo	Brodalumab 140 mg	Brodalumab 210 mg
Number of subjects analysed	220	219	222
Units: percentage of participants
number (confidence interval 95%)
Week 1	0.9 (0.1 to 3.2)	10 (6.4 to 14.8)	26.1 (20.5 to 32.4)
Week 2	2.7 (1 to 5.8)	47.9 (41.2 to 54.8)	62.2 (55.4 to 68.6)
Week 4	5.5 (2.8 to 9.3)	69.9 (63.3 to 75.9)	87.4 (82.3 to 91.5)
Week 6	7.3 (4.2 to 11.5)	75.3 (69.1 to 80.9)	88.3 (83.3 to 92.2)
Week 8	9.5 (6 to 14.2)	75.3 (69.1 to 80.9)	86.5 (81.3 to 90.7)
Week 10	7.7 (4.6 to 12.1)	73.5 (67.1 to 79.2)	85.1 (79.8 to 89.5)
Week 12	7.7 (4.6 to 12.1)	73.5 (67.1 to 79.2)	88.3 (83.3 to 92.2)

No statistical analyses for this end point

Secondary: Percentage of Participants with a PASI 90 at Each Visit in the Induction Phase

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End point title

Percentage of Participants with a PASI 90 at Each Visit in the Induction Phase

End point description

The PASI measures the average redness (erythema), thickness (induration), and scaliness (each graded on a 0 to 4 scale) of psoriasis lesions, weighted by the area of involvement in the four main body areas (i.e., head and neck, trunk, upper extremities, and lower extremities). PASI scores can range from 0.0 to 72.0, with higher scores indicating greater severity and/or more extensive psoriasis. A PASI 90% response is a 90% or greater improvement from baseline. Non-responder imputation (NRI) was used to impute missing data.

End point type

Secondary

End point timeframe

Baseline and Weeks 1, 2, 4, 6, 8, 10, and 12

End point values	Placebo	Brodalumab 140 mg	Brodalumab 210 mg
Number of subjects analysed	220	219	222
Units: percentage of participants
number (confidence interval 95%)
Week 1	0 (0 to 1.7)	0.5 (0 to 2.5)	0 (0 to 1.6)
Week 2	0 (0 to 1.7)	3.2 (1.3 to 6.5)	5.4 (2.8 to 9.3)
Week 4	0.5 (0 to 2.5)	21.5 (16.2 to 27.5)	30.2 (24.2 to 36.7)
Week 6	0.5 (0 to 2.5)	32.9 (26.7 to 39.5)	49.1 (42.3 to 55.9)
Week 8	0.5 (0 to 2.5)	39.7 (33.2 to 46.5)	62.6 (55.9 to 69)
Week 10	0.9 (0.1 to 3.2)	43.4 (36.7 to 50.2)	67.1 (60.5 to 73.3)
Week 12	0.9 (0.1 to 3.2)	42.5 (35.8 to 49.3)	70.3 (63.8 to 76.2)

No statistical analyses for this end point

Secondary: Percent Improvement From Baseline in PASI During the Induction Phase

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End point title

Percent Improvement From Baseline in PASI During the Induction Phase

End point description

The PASI measures the average redness (erythema), thickness (induration), and scaliness (each graded on a 0 to 4 scale) of psoriasis lesions, weighted by the area of involvement in the four main body areas (i.e., head and neck, trunk, upper extremities, and lower extremities). PASI scores can range from 0.0 to 72.0, with higher scores indicating greater severity and/or more extensive psoriasis. This endpoint was analyzed in subjects with a valid measurement value at each time point. Percent improvement from baseline is calculated as: (Baseline – Post-baseline) / Baseline * 100.

End point type

Secondary

End point timeframe

Baseline and weeks 1, 2, 4, 6, 8, 10 and 12

End point values	Placebo	Brodalumab 140 mg	Brodalumab 210 mg
Number of subjects analysed	220	219	222
Units: percent improvement
arithmetic mean (standard deviation)
Week 1 (N = 215, 215, 219)	1.95 ( 15.03 )	22.1 ( 21.06 )	32.6 ( 23.09 )
Week 2 (N = 213, 215, 213)	1.52 ( 23.23 )	45.5 ( 27.67 )	55.59 ( 24.75 )
Week 4 (N = 216, 214, 216)	1.12 ( 28.59 )	63.1 ( 30.38 )	75.16 ( 26.63 )
Week 6 (N = 210, 215, 211)	3.46 ( 30.87 )	70.11 ( 32.27 )	83.78 ( 21.55 )
Week 8 (N = 212, 206, 206)	0.94 ( 37.11 )	73.21 ( 32.23 )	87.19 ( 21.37 )
Week 10 (N = 203, 202, 206)	-1.26 ( 38.96 )	74.33 ( 33.43 )	88.29 ( 22.18 )
Week 12 (N = 209, 208, 212)	-3.15 ( 40.53 )	70.69 ( 37.24 )	87.58 ( 25.56 )

No statistical analyses for this end point

Secondary: Absolute PASI Score During the Induction Phase

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End point title

Absolute PASI Score During the Induction Phase

End point description

End point type

Secondary

End point timeframe

Weeks 1, 2, 4, 6, 8, 10 and 12

End point values	Placebo	Brodalumab 140 mg	Brodalumab 210 mg
Number of subjects analysed	220	219	222
Units: units on a scale
arithmetic mean (standard deviation)
Week 1 (N = 215, 215, 219)	19.16 ( 7.53 )	15.58 ( 7.16 )	13.3 ( 7.13 )
Week 2 (N = 213, 215, 213)	19.35 ( 8.32 )	10.98 ( 7.08 )	8.7 ( 5.83 )
Week 4 (N = 216, 214, 216)	19.33 ( 8.74 )	7.34 ( 7 )	4.85 ( 5.28 )
Week 6 (N = 210, 215, 211)	18.89 ( 8.96 )	6.13 ( 7.46 )	3.21 ( 4.68 )
Week 8 (N = 212, 206, 206)	19.34 ( 10.03 )	5.59 ( 7.69 )	2.6 ( 4.74 )
Week 10 (N = 203, 202, 206)	19.85 ( 10.36 )	5.49 ( 8.02 )	2.34 ( 4.8 )
Week 12 (N = 209, 208, 212)	19.99 ( 10.49 )	6.08 ( 8.59 )	2.52 ( 5.74 )

No statistical analyses for this end point

Secondary: Body Surface Area Involvement During the Induction Phase

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End point title

Body Surface Area Involvement During the Induction Phase

End point description

This endpoint was analyzed in subjects with a valid measurement value at each time point.

End point type

Secondary

End point timeframe

Weeks 1, 2, 4, 6, 8, 10 and 12

End point values	Placebo	Brodalumab 140 mg	Brodalumab 210 mg
Number of subjects analysed	220	219	222
Units: Percent involvement
arithmetic mean (standard deviation)
Week 1 (N = 215, 215, 219)	26.92 ( 16.98 )	25.81 ( 16.78 )	22.48 ( 15.01 )
Week 2 (N = 213, 215, 213)	27.83 ( 17.61 )	21.33 ( 15.62 )	17.74 ( 13.31 )
Week 4 (N = 216, 214, 216)	28.55 ( 18.26 )	15.34 ( 14.59 )	11.84 ( 12.88 )
Week 6 (N = 210, 215, 211)	28.27 ( 18.42 )	12.64 ( 15.78 )	8.37 ( 12.3 )
Week 8 (N = 212, 206, 206)	29.16 ( 19.03 )	11.05 ( 15.78 )	6.71 ( 11.17 )
Week 10 (N = 203, 202, 206)	29.68 ( 19.76 )	10.38 ( 16.2 )	5.77 ( 11.18 )
Week 12 (N = 208, 208, 212)	29.8 ( 20.2 )	11.03 ( 16.73 )	5.39 ( 11.86 )

No statistical analyses for this end point

Secondary: Improvement From Baseline in NAPSI Score at Week 12

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End point title

Improvement From Baseline in NAPSI Score at Week 12

End point description

The NAPSI scale is an objective, numeric, and reproducible grading system for nail psoriasis that incorporates the many different features of nail psoriasis. Each quarter of the nail was scored for the presence (1) or absence (0) of 8 clinical features for a score of 0-4 for each feature. The total score for each nail ranges from 0 (absent) to 32 (worst). Results are reported for the worst nail for subjects with baseline nail involvement (NAPSI score ≥ 6) with a valid measurement at week 12. Improvement from baseline is calculated as: Baseline value – Post-baseline value.

End point type

Secondary

End point timeframe

Baseline and week 12

End point values	Placebo	Brodalumab 140 mg	Brodalumab 210 mg
Number of subjects analysed	56	62	59
Units: units on a scale
arithmetic mean (standard deviation)	0.6 ( 3 )	3.6 ( 4 )	4.6 ( 3.5 )

No statistical analyses for this end point

Secondary: Percent Improvement From Baseline in Psoriasis Scalp Severity Index Score

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End point title

Percent Improvement From Baseline in Psoriasis Scalp Severity Index Score

End point description

The Psoriasis Scalp Severity Index (PSSI) measures the extent of psoriasis involvement and the severity of erythema, infiltration, and desquamation of the scalp. Involvement and severity of psoriasis for the PSSI is scored by physicians using a scale from 0 to 72, where 0 = no psoriasis, and higher scores indicating more severe disease. The PSSI calculation does not include the face or neck area. Results are reported for subjects with a PSSI ≥ 15 and SSA ≥ 30 at baseline and with a valid measurement value at each time point. Percent improvement from baseline is calculated as: (Baseline – Post-baseline) / Baseline * 100.

End point type

Secondary

End point timeframe

Baseline and weeks 2, 4, 8, and 12

End point values	Placebo	Brodalumab 140 mg	Brodalumab 210 mg
Number of subjects analysed	95	105	82
Units: percent improvement
arithmetic mean (standard deviation)
Week 2 (N = 91, 102, 78)	6.69 ( 33.91 )	59.02 ( 37.94 )	67.58 ( 28.83 )
Week 4 (N = 94, 102, 79)	7.06 ( 37.54 )	75.12 ( 32.81 )	87.54 ( 20.87 )
Week 8 (N = 91, 99, 77)	13.42 ( 47.91 )	75.3 ( 37.04 )	92.97 ( 14.04 )
Week 12 (N = 90, 100, 81)	14.42 ( 42.77 )	73.28 ( 40.24 )	92.83 ( 13.94 )

No statistical analyses for this end point

Secondary: Improvement From Study Baseline in Scalp Surface Area (SSA) During the Induction Phase

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End point title

Improvement From Study Baseline in Scalp Surface Area (SSA) During the Induction Phase

End point description

Results are reported for subjects with a PSSI ≥ 15 and SSA ≥ 30 at baseline with a valid measurement value at each time point.

End point type

Secondary

End point timeframe

Baseline and weeks 2, 4, 8 and 12

End point values	Placebo	Brodalumab 140 mg	Brodalumab 210 mg
Number of subjects analysed	95	105	82
Units: percent
arithmetic mean (standard deviation)
Week 2 (N = 91, 102, 78)	7.58 ( 21.54 )	26.3 ( 28.56 )	29.56 ( 26.38 )
Week 4 (N = 94, 102, 79)	6.19 ( 21.23 )	38.07 ( 28.49 )	44.53 ( 26.38 )
Week 8 (N = 91, 99, 77)	8.61 ( 23.11 )	41.98 ( 29.09 )	52.58 ( 24.71 )
Week 12 (N = 90, 100, 81)	8.68 ( 26.5 )	41.92 ( 29.48 )	52.53 ( 22.92 )

No statistical analyses for this end point

Secondary: Percentage of Participants with an sPGA of Clear at Week 52

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End point title

Percentage of Participants with an sPGA of Clear at Week 52

End point description

Physician’s global assessment of the subject’s psoriasis based on the severity of induration, scaling, and erythema assessed on a 6-point scale ranging from 0 (clear) to 5 (very severe). A sPGA response is defined as a sPGA value of clear (score 0) at week 52. This endpoint was analyzed in subjects rerandomized into the withdrawal phase. Non-responder imputation (NRI) was used to impute missing data; subjects who experienced return of disease through week 52 were imputed as non-responders at the time of qualification.

End point type

Secondary

End point timeframe

Week 52

End point values	Brodalumab 140 mg / Placebo	Brodalumab 140 mg / Brodalumab 140 mg	Brodalumab 210 mg / Placebo	Brodalumab 210 mg / Brodalumab 210 mg
Number of subjects analysed	59	57	84	83
Units: percentage of participants
number (confidence interval 95%)	1.7 (0 to 9.1)	43.9 (30.7 to 57.6)	0 (0 to 4.3)	67.5 (56.3 to 77.4)

No statistical analyses for this end point

Secondary: Percentage of Participants with a PASI 75 at Week 52

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End point title

Percentage of Participants with a PASI 75 at Week 52

End point description

The PASI measures the average redness (erythema), thickness (induration), and scaliness (each graded on a 0 to 4 scale) of psoriasis lesions, weighted by the area of involvement in the four main body areas (i.e., head and neck, trunk, upper extremities, and lower extremities). PASI scores can range from 0.0 to 72.0, with higher scores indicating greater severity and/or more extensive psoriasis. This endpoint was analyzed in subjects rerandomized into the withdrawal phase. Non-responder imputation was used to impute missing data; subjects who experienced return of disease and/or inadequate response that resulted in a protocol-specified treatment change at or before week 52 were also imputed as non-responders.

End point type

Secondary

End point timeframe

Baseline and week 52

End point values	Brodalumab 140 mg / Placebo	Brodalumab 140 mg / Brodalumab 140 mg	Brodalumab 210 mg / Placebo	Brodalumab 210 mg / Brodalumab 210 mg
Number of subjects analysed	59	57	84	83
Units: percentage of participants
number (confidence interval 95%)	8.5 (2.8 to 18.7)	82.5 (70.1 to 91.3)	0 (0 to 4.3)	90.4 (81.9 to 95.7)

No statistical analyses for this end point

Secondary: Percentage of Participants with a PASI 90 at Week 52

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End point title

Percentage of Participants with a PASI 90 at Week 52

End point description

The PASI measures the average redness (erythema), thickness (induration), and scaliness (each graded on a 0 to 4 scale) of psoriasis lesions, weighted by the area of involvement in the four main body areas (i.e., head and neck, trunk, upper extremities, and lower extremities). PASI scores can range from 0.0 to 72.0, with higher scores indicating greater severity and/or more extensive psoriasis. This endpoint was analyzed in subjects rerandomized into the withdrawal phase. Non-responder imputation was used to impute missing data; subjects who experienced return of disease and/or inadequate response that resulted in a protocol-specified treatment change at or before week 52 were also imputed as non-responders.

End point type

Secondary

End point timeframe

Baseline and week 52

End point values	Brodalumab 140 mg / Placebo	Brodalumab 140 mg / Brodalumab 140 mg	Brodalumab 210 mg / Placebo	Brodalumab 210 mg / Brodalumab 210 mg
Number of subjects analysed	59	57	84	83
Units: percentage of participants
number (confidence interval 95%)	3.4 (0.4 to 11.7)	66.7 (52.9 to 78.6)	0 (0 to 4.3)	79.5 (69.2 to 87.6)

No statistical analyses for this end point

Secondary: Percentage of Participants with a PASI 100 at Week 52

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End point title

Percentage of Participants with a PASI 100 at Week 52

End point description

The PASI measures the average redness (erythema), thickness (induration), and scaliness (each graded on a 0 to 4 scale) of psoriasis lesions, weighted by the area of involvement in the four main body areas (i.e., head and neck, trunk, upper extremities, and lower extremities). PASI scores can range from 0.0 to 72.0, with higher scores indicating greater severity and/or more extensive psoriasis. This endpoint was analyzed in subjects rerandomized into the withdrawal phase. Non-responder imputation was used to impute missing data; subjects who experienced return of disease and/or inadequate response that resulted in a protocol-specified treatment change at or before week 52 were also imputed as non-responders.

End point type

Secondary

End point timeframe

Baseline and week 52

End point values	Brodalumab 140 mg / Placebo	Brodalumab 140 mg / Brodalumab 140 mg	Brodalumab 210 mg / Placebo	Brodalumab 210 mg / Brodalumab 210 mg
Number of subjects analysed	59	57	84	83
Units: percentage of participants
number (confidence interval 95%)	1.7 (0 to 9.1)	43.9 (30.7 to 57.6)	0 (0 to 4.3)	67.5 (56.3 to 77.4)

No statistical analyses for this end point

Secondary: Percent Improvement From Baseline in PASI Score During the Withdrawal Phase

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End point title

Percent Improvement From Baseline in PASI Score During the Withdrawal Phase

End point description

The PASI measures the average redness (erythema), thickness (induration), and scaliness (each graded on a 0 to 4 scale) of psoriasis lesions, weighted by the area of involvement in the four main body areas (i.e., head and neck, trunk, upper extremities, and lower extremities). PASI scores can range from 0.0 to 72.0, with higher scores indicating greater severity and/or more extensive psoriasis. This endpoint was analyzed in subjects re-randomized into the withdrawal phase with a valid measurement at each time point. Percent improvement from baseline is calculated as: (Baseline – Post-baseline) / Baseline * 100.

End point type

Secondary

End point timeframe

Baseline and weeks 12, 16, 24, 36, and 52

End point values	Brodalumab 140 mg / Placebo	Brodalumab 140 mg / Brodalumab 140 mg	Brodalumab 210 mg / Placebo	Brodalumab 210 mg / Brodalumab 210 mg
Number of subjects analysed	59	57	84	83
Units: percent improvement
arithmetic mean (standard deviation)
Week 12 (N = 59, 57, 84, 83)	94.72 ( 7.69 )	94.16 ( 7.1 )	97.07 ( 4.42 )	96.43 ( 6.87 )
Week 16 (N = 58, 54, 82, 83)	76.53 ( 23.41 )	94.73 ( 7.23 )	84.45 ( 23.27 )	95.76 ( 6.96 )
Week 24 (N = 20, 53, 26, 78)	78.15 ( 21.07 )	94.84 ( 8.41 )	67.94 ( 22.29 )	96.83 ( 5.41 )
Week 36 (N = 11, 48, 9, 77)	76.25 ( 28.41 )	94.9 ( 9.45 )	57.53 ( 46.43 )	97.57 ( 7.38 )
Week 52 (N = 6, 47, 2, 72)	84 ( 14.33 )	94.69 ( 9.13 )	61.51 ( 5.17 )	98.18 ( 3.82 )

No statistical analyses for this end point

Secondary: Time to sPGA Response During the Retreatment Phase

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End point title

Time to sPGA Response During the Retreatment Phase

End point description

Time to sPGA success is calculated as the time from qualification for retreatment to the assessment day of first sPGA response. Response is an sPGA score of 0 (clear) or 1 (almost clear). Time to sPGA response was analyzed using Kaplan-Meier methods in subjects who entered the retreatment phase. Subjects who discontinued prior to study day 392 or qualified for rescue were censored at the date of the last assessment taken prior to or on the early termination visit or last assessment taken prior to or on the date of qualification for rescue treatment, whichever occurred first. Continuing subjects who reached study day 392 or qualified for rescue treatment without achieving response were censored at the date of the last assessment taken prior to or on day 392 or at the rescue qualification date, whichever occurred first. "99999" indicates data that could not be estimated due to the low number of events.

End point type

Secondary

End point timeframe

Week 16 to week 52

End point values	Brodalumab 140 mg / Placebo / Brodalumab 140 mg	Brodalumab 140 mg / Brodalumab 140 mg /Brodalumab 140 mg	Brodalumab 210 mg / Placebo / Brodalumab 210 mg	Brodalumab 210 mg / Brodalumab 210 mg / Brodalumab 210 mg
Number of subjects analysed	53	12	79	5
Units: weeks
median (confidence interval 95%)	4.14 (4.14 to 4.29)	15 (2.29 to 99999)	4.14 (4.14 to 4.86)	99999 (2 to 99999)

No statistical analyses for this end point

Secondary: Time to PASI 75 Response During the Retreatment Phase

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End point title

Time to PASI 75 Response During the Retreatment Phase

End point description

Time to PASI 75 response was calculated from the date of qualification for retreatment to the assessment day of first PASI 75 response. The analysis includes subjects who entered the retreatment phase and were not PASI 75 responders at the retreatment qualification date. Time to PASI response was analyzed using Kaplan-Meier methods. Subjects who discontinued prior to study day 392 or qualified for rescue were censored at the date of the last assessment taken prior to or on the early termination visit or last assessment taken prior to or on the date of qualification for rescue treatment, whichever occurred first. Continuing subjects who reached study day 392 or qualified for rescue treatment without achieving response were censored at the date of the last assessment taken prior to or on day 392 or at the rescue qualification date, whichever occurred first. "99999" indicates data that could not be estimated due to the low number of events.

End point type

Secondary

End point timeframe

Week 16 to week 52

End point values	Brodalumab 140 mg / Placebo / Brodalumab 140 mg	Brodalumab 140 mg / Brodalumab 140 mg /Brodalumab 140 mg	Brodalumab 210 mg / Placebo / Brodalumab 210 mg	Brodalumab 210 mg / Brodalumab 210 mg / Brodalumab 210 mg
Number of subjects analysed	47	5	70	2
Units: weeks
median (confidence interval 95%)	3.71 (2.14 to 4.14)	99999 (11.14 to 99999)	4.14 (2.29 to 4.14)	9.36 (8.57 to 10.14)

No statistical analyses for this end point

Secondary: Time to PASI 90 Response During the Retreatment Phase

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End point title

Time to PASI 90 Response During the Retreatment Phase

End point description

Time to PASI 90 response was calculated from the date of qualification for retreatment to the assessment day of first PASI 90 response. The analysis includes subjects who entered the retreatment phase and were not PASI 90 responders at the retreatment qualification date. Time to PASI response was analyzed using Kaplan-Meier methods. Subjects who discontinued prior to study day 392 or qualified for rescue were censored at the date of the last assessment taken prior to or on the early termination visit or last assessment taken prior to or on the date of qualification for rescue treatment, whichever occurred first. Continuing subjects who reached study day 392 or qualified for rescue treatment without achieving response were censored at the date of the last assessment taken prior to or on day 392 or at the rescue qualification date, whichever occurred first. "99999" indicates data that could not be estimated due to the low number of events.

End point type

Secondary

End point timeframe

Week 16 to week 52

End point values	Brodalumab 140 mg / Placebo / Brodalumab 140 mg	Brodalumab 140 mg / Brodalumab 140 mg /Brodalumab 140 mg	Brodalumab 210 mg / Placebo / Brodalumab 210 mg	Brodalumab 210 mg / Brodalumab 210 mg / Brodalumab 210 mg
Number of subjects analysed	53	12	79	5
Units: weeks
median (confidence interval 95%)	4.21 (4.14 to 6.14)	15 (2.29 to 99999)	4.43 (4.14 to 6.14)	10.14 (2 to 99999)

No statistical analyses for this end point

Secondary: Time to PASI 100 Response During the Retreatment Phase

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End point title

Time to PASI 100 Response During the Retreatment Phase

End point description

Time to PASI 100 response was calculated from the date of qualification for retreatment to the assessment day of first PASI 100 response. The analysis includes subjects who entered the retreatment phase and were not PASI 100 responders at the retreatment qualification date. Time to PASI response was analyzed using Kaplan-Meier methods. Subjects who discontinued prior to study day 392 or qualified for rescue were censored at the date of the last assessment taken prior to or on the early termination visit or last assessment taken prior to or on the date of qualification for rescue treatment, whichever occurred first. Continuing subjects who reached study day 392 or qualified for rescue treatment without achieving response were censored at the date of the last assessment taken prior to or on day 392 or at the rescue qualification date, whichever occurred first. "99999" indicates data that could not be estimated due to the low number of events.

End point type

Secondary

End point timeframe

Week 16 to week 52

End point values	Brodalumab 140 mg / Placebo / Brodalumab 140 mg	Brodalumab 140 mg / Brodalumab 140 mg /Brodalumab 140 mg	Brodalumab 210 mg / Placebo / Brodalumab 210 mg	Brodalumab 210 mg / Brodalumab 210 mg / Brodalumab 210 mg
Number of subjects analysed	53	12	79	5
Units: weeks
median (confidence interval 95%)	11.71 (6.43 to 20.14)	99999 (4.14 to 99999)	8.14 (6.14 to 9)	99999 (99999 to 99999)

No statistical analyses for this end point

Secondary: Percentage of Participants with an sPGA Response During the Retreatment Phase

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End point title

Percentage of Participants with an sPGA Response During the Retreatment Phase

End point description

A sPGA response is defined as a sPGA value of clear (score 0) or almost clear (score 1). Results are reported by weeks since return of disease."N" indicates the number of subjects who entered the retreatment phase and had a valid measurement value at the specified week of retreatment.

End point type

Secondary

End point timeframe

Week 16 to week 52

End point values	Brodalumab 140 mg / Placebo / Brodalumab 140 mg	Brodalumab 140 mg / Brodalumab 140 mg /Brodalumab 140 mg	Brodalumab 210 mg / Placebo / Brodalumab 210 mg	Brodalumab 210 mg / Brodalumab 210 mg / Brodalumab 210 mg
Number of subjects analysed	53	12	79	5
Units: percentage of participants
number (confidence interval 95%)
2 weeks (N = 39, 4, 56, 2)	30.8 (17 to 47.6)	25 (0.6 to 80.6)	33.9 (21.8 to 47.8)	50 (1.3 to 98.7)
4 weeks (N = 48, 7, 62, 4)	70.8 (55.9 to 83)	14.3 (0.4 to 57.9)	69.4 (56.3 to 80.4)	25 (0.6 to 80.6)
8 weeks (N = 36, 7, 45, 3)	77.8 (60.8 to 89.9)	14.3 (0.4 to 57.9)	80 (65.4 to 90.4)	66.7 (9.4 to 99.2)
12 weeks (N = 33, 7, 40, 2)	72.7 (54.5 to 86.7)	14.3 (0.4 to 57.9)	80 (64.4 to 90.9)	100 (15.8 to 100)
16 weeks (N = 33, 3, 38, 2)	81.8 (64.5 to 93)	0 (0 to 70.8)	81.6 (65.7 to 92.3)	100 (15.8 to 100)
20 weeks (N = 27, 3, 34, 2)	81.5 (61.9 to 93.7)	66.7 (9.4 to 99.2)	88.2 (72.5 to 96.7)	0 (0 to 84.2)
24 weeks (N = 19, 1, 32, 1)	84.2 (60.4 to 96.6)	0 (0 to 97.5)	96.9 (83.8 to 99.9)	0 (0 to 97.5)

No statistical analyses for this end point

Secondary: Percentage of Participants with a PASI 75 Response During the Retreatment Phase

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End point title

Percentage of Participants with a PASI 75 Response During the Retreatment Phase

End point description

Results are reported by weeks since return of disease."N" indicates the number of subjects who entered the retreatment phase and had a valid measurement value at the specified week of retreatment.

End point type

Secondary

End point timeframe

Week 16 to week 52

End point values	Brodalumab 140 mg / Placebo / Brodalumab 140 mg	Brodalumab 140 mg / Brodalumab 140 mg /Brodalumab 140 mg	Brodalumab 210 mg / Placebo / Brodalumab 210 mg	Brodalumab 210 mg / Brodalumab 210 mg / Brodalumab 210 mg
Number of subjects analysed	53	12	79	5
Units: percentage of participants
number (confidence interval 95%)
2 weeks (N = 39, 4, 56, 2)	66.7 (49.8 to 80.9)	75 (19.4 to 99.4)	67.9 (54 to 79.7)	50 (1.3 to 98.7)
4 weeks (N = 48, 7, 62, 4)	85.4 (72.2 to 93.9)	42.9 (9.9 to 81.6)	83.9 (72.3 to 92)	50 (6.8 to 93.2)
8 weeks (N = 36, 7, 45, 3)	86.1 (70.5 to 95.3)	14.3 (0.4 to 57.9)	91.1 (78.8 to 97.5)	100 (29.2 to 100)
12 weeks (N = 33, 7, 40, 2)	78.8 (61.1 to 91)	57.1 (18.4 to 90.1)	92.5 (79.6 to 98.4)	100 (15.8 to 100)
16 weeks (N = 33, 3, 38, 2)	84.8 (68.1 to 94.9)	66.7 (9.4 to 99.2)	92.1 (78.6 to 98.3)	100 (15.8 to 100)
20 weeks (N = 27, 3, 34, 2)	100 (87.2 to 100)	100 (29.2 to 100)	94.1 (80.3 to 99.3)	50 (1.3 to 98.7)
24 weeks (N = 19, 1, 32, 1)	94.7 (74 to 99.9)	100 (2.5 to 100)	100 (89.1 to 100)	100 (2.5 to 100)

No statistical analyses for this end point

Secondary: Percentage of Participants with a PASI 90 Response During the Retreatment Phase

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End point title

Percentage of Participants with a PASI 90 Response During the Retreatment Phase

End point description

Results are reported by weeks since return of disease. "N" indicates the number of subjects who entered the retreatment phase and had a valid measurement value at the specified week of retreatment.

End point type

Secondary

End point timeframe

Week 16 to week 52

End point values	Brodalumab 140 mg / Placebo / Brodalumab 140 mg	Brodalumab 140 mg / Brodalumab 140 mg /Brodalumab 140 mg	Brodalumab 210 mg / Placebo / Brodalumab 210 mg	Brodalumab 210 mg / Brodalumab 210 mg / Brodalumab 210 mg
Number of subjects analysed	53	12	79	5
Units: percentage of participants
number (confidence interval 95%)
2 weeks (N = 39, 4, 56, 2)	23.1 (11.1 to 39.3)	25 (0.6 to 80.6)	28.6 (17.3 to 42.2)	50 (1.3 to 98.7)
4 weeks (N = 48, 7, 62, 4)	62.5 (47.4 to 76)	28.6 (3.7 to 71)	59.7 (46.4 to 71.9)	25 (0.6 to 80.6)
8 weeks (N = 36, 7, 45, 3)	75 (57.8 to 87.9)	0 (0 to 41)	88.9 (75.9 to 96.3)	66.7 (9.4 to 99.2)
12 weeks (N = 33, 7, 40, 2)	63.6 (45.1 to 79.6)	14.3 (0.4 to 57.9)	85 (70.2 to 94.3)	50 (1.3 to 98.7)
16 weeks (N = 33, 3, 38, 2)	72.7 (54.5 to 86.7)	33.3 (0.8 to 90.6)	86.8 (71.9 to 95.6)	50 (1.3 to 98.7)
20 weeks (N = 27, 3, 34, 2)	70.4 (49.8 to 86.2)	0 (0 to 70.8)	91.2 (76.3 to 98.1)	0 (0 to 84.2)
24 weeks (N = 19, 1, 32, 1)	78.9 (54.4 to 93.9)	0 (0 to 97.5)	96.9 (83.8 to 99.9)	0 (0 to 97.5)

No statistical analyses for this end point

Secondary: Percentage of Participants with a PASI 100 Response During the Retreatment Phase

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End point title

Percentage of Participants with a PASI 100 Response During the Retreatment Phase

End point description

Results are reported by weeks since return of disease. "N" indicates the number of subjects who entered the retreatment phase and had a valid measurement value at the specified week of retreatment.

End point type

Secondary

End point timeframe

Week 16 to week 52

End point values	Brodalumab 140 mg / Placebo / Brodalumab 140 mg	Brodalumab 140 mg / Brodalumab 140 mg /Brodalumab 140 mg	Brodalumab 210 mg / Placebo / Brodalumab 210 mg	Brodalumab 210 mg / Brodalumab 210 mg / Brodalumab 210 mg
Number of subjects analysed	53	12	79	5
Units: percentage of participants
number (confidence interval 95%)
2 weeks (N = 39, 4, 56, 2)	5.1 (0.6 to 17.3)	0 (0 to 60.2)	10.7 (4 to 21.9)	0 (0 to 84.2)
4 weeks (N = 48, 7, 62, 4)	27.1 (15.3 to 41.8)	14.3 (0.4 to 57.9)	33.9 (22.3 to 47)	0 (0 to 60.2)
8 weeks (N = 36, 7, 45, 3)	38.9 (23.1 to 56.5)	0 (0 to 41)	64.4 (48.8 to 78.1)	0 (0 to 70.8)
12 weeks (N = 33, 7, 40, 2)	45.5 (28.1 to 63.6)	0 (0 to 41)	60 (43.3 to 75.1)	0 (0 to 84.2)
16 weeks (N = 33, 3, 38, 2)	60.6 (42.1 to 77.1)	0 (0 to 70.8)	65.8 (48.6 to 80.4)	0 (0 to 84.2)
20 weeks (N = 27, 3, 34, 2)	63 (42.4 to 80.6)	0 (0 to 70.8)	79.4 (62.1 to 91.3)	0 (0 to 84.2)
24 weeks (N = 19, 1, 32, 1)	68.4 (43.4 to 87.4)	0 (0 to 97.5)	84.4 (67.2 to 94.7)	0 (0 to 97.5)

No statistical analyses for this end point

Secondary: Percentage of Participants with a Dermatology Life Quality Index (DLQI) Response at Week 12

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End point title

Percentage of Participants with a Dermatology Life Quality Index (DLQI) Response at Week 12

End point description

The dermatology life quality index (DLQI) is a skin disease-specific instrument to evaluate health-related quality of life. The DLQI questionnaire asks participants to evaluate the degree that psoriasis has affected their quality of life in the last week, and includes the following parameters: symptoms and feelings, daily activities, leisure activities, work or school activities, personal relationships and treatment related feelings. Participants answered 10 questions on a scale from 0 (not at all) to 3 (very much); the range of the total score is from 0 (best possible score) to 30 (worst possible score). A DLQI response is defined as achieving at least a 5-point improvement from baseline. This endpoint was analyzed in subjects with a baseline DLQI ≥ 5. Non-responder imputation was used to impute missing data.

End point type

Secondary

End point timeframe

Baseline and week 12

End point values	Placebo	Brodalumab 140 mg	Brodalumab 210 mg
Number of subjects analysed	199	191	201
Units: percentage of participants
number (confidence interval 95%)	21.6 (16.1 to 28)	73.8 (67 to 79.9)	83.6 (77.7 to 88.4)

No statistical analyses for this end point

Secondary: Treatment Satisfaction at Week 12

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End point title

Treatment Satisfaction at Week 12

End point description

Subjects assessed their satisfaction with their treatment as dissatisfied, very dissatisfied, neither satisfied nor dissatisfied, satisfied, or very satisfied. This endpoint was analyzed in subjects who had a valid measurement value at week 12.

End point type

Secondary

End point timeframe

Week 12

End point values	Placebo	Brodalumab 140 mg	Brodalumab 210 mg
Number of subjects analysed	205	208	209
Units: participants
number (not applicable)
Very dissatisfied	60	15	16
Dissatisfied	55	21	5
Neither satisfied nor dissatisfied	48	20	10
Satisfied	28	52	57
Very satisfied	14	100	121

No statistical analyses for this end point

Secondary: Medical Outcomes Short Form-36 (SF-36) Mental and Physical Component Scores at Week 12

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End point title

Medical Outcomes Short Form-36 (SF-36) Mental and Physical Component Scores at Week 12

End point description

The SF-36 assesses the general quality of life (QOL) of participants by evaluating the domains of physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. The questionnaire consists of 36 questions that are completed by the participant. The SF-36 is split into two major components: physical health and mental health. Under physical health are the following four domains: physical health, bodily pain, physical functioning and physical role limitations. Under the mental health domain there are four domains; mental health, vitality, social functioning, and emotional role limitation. The individual domain scores are aggregated to derive a physical-component summary score and a mental-component summary score which range from 0 to 100, with higher scores indicating a better level of functioning. This endpoint was analyzed in subjects who had a valid measurement value at week 12.

End point type

Secondary

End point timeframe

Week 12

End point values	Placebo	Brodalumab 140 mg	Brodalumab 210 mg
Number of subjects analysed	205	207	208
Units: units on a scale
arithmetic mean (standard deviation)
Physical Component Score	46.52 ( 9.82 )	51.96 ( 7.8 )	51.03 ( 8.98 )
Mental Component Score	46.43 ( 11.48 )	50.82 ( 9.19 )	51.86 ( 8.88 )

No statistical analyses for this end point

Secondary: EuroQoL-5 Dimension (EQ-5D) Score at Week 12

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End point title

EuroQoL-5 Dimension (EQ-5D) Score at Week 12

End point description

The EQ-5D questionnaire captures 2 types of information, a descriptive “profile,” (health state), and an overall health rating using a visual analog scale. The health states include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, which are combined to produce a single weighted index score by applying coefficients from a validated value set. The visual analog scale is a linear, thermometer-like scale that respondents can use to rate their health status, with zero representing the worst imaginable health status and 100 the best. The EQ-5D score was calculated based on the five attributes on the EQ-5D questionnaire, each answered 1, 2, or 3, with 1 signifying no problem, 2 signifying some problem, and 3 signifying major problem. The calculated EQ-5D score ranges from -0.594 to 1, with -0.594 representing death and 1 representing the perfect health state. This endpoint was analyzed in subjects who had a valid measurement value at week 12.

End point type

Secondary

End point timeframe

Week 12

End point values	Placebo	Brodalumab 140 mg	Brodalumab 210 mg
Number of subjects analysed	205	207	209
Units: units on a scale
arithmetic mean (standard deviation)	0.6226 ( 0.3196 )	0.8322 ( 0.2391 )	0.8584 ( 0.2135 )

No statistical analyses for this end point

Secondary: Improvement From Baseline in Hospital Anxiety and Depression Scale (HADS) Score at Week 12

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End point title

Improvement From Baseline in Hospital Anxiety and Depression Scale (HADS) Score at Week 12

End point description

The HADS is a 14-item questionnaire assessing subject’s symptoms of depression and anxiety. The measure consists of 7 items reflecting anxiety and 7 items reflecting depression. Each item is answered by the patient on a 4-point (0–3) response category so the possible scores ranged from 0 to 21 for anxiety and 0 to 21 for depression. This endpoint was analyzed in subjects who had a valid measurement value at week 12. Improvement from baseline was calculated as Baseline value - Post-baseline value.

End point type

Secondary

End point timeframe

Baseline and week 12

End point values	Placebo	Brodalumab 140 mg	Brodalumab 210 mg
Number of subjects analysed	204	204	208
Units: units on a scale
arithmetic mean (standard deviation)
Depression Score	-0.1 ( 3 )	1.7 ( 3.4 )	2 ( 3.4 )
Anxiety Score	0.2 ( 2.8 )	1.4 ( 3.4 )	1.8 ( 3.3 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Induction Phase: 12 weeks Overall Study: Up to 266 weeks

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

18.0

Reporting group title

Induction Phase: Placebo

Reporting group description

Participants received placebo matching brodalumab administered via subcutaneous injection on day 1 and at weeks 1, 2, 4, 6, 8, and 10.

Reporting group title

Induction Phase: Brodalumab 140 mg

Reporting group description

Participants received 140 mg brodalumab via subcutaneous injection on day 1 and at weeks 1, 2, 4, 6, 8, and 10.

Reporting group title

Induction Phase: Brodalumab 210 mg

Reporting group description

Participants received 210 mg brodalumab via subcutaneous injection on day 1 and at weeks 1, 2, 4, 6, 8, and 10.

Reporting group title

Overall Study: Brodalumab Variable Dosing

Reporting group description

Participants who received either combination dosing of brodalumab (140 mg and 210 mg) during the overall study or who received fewer than 75% of doses of brodalumab after first dose of active treatment.

Reporting group title

Overall Study: Brodalumab 140 mg

Reporting group description

Participants who received at least 75% of doses with brodalumab 140 mg after the first active dose and no doses of 210 mg during the overall study.

Reporting group title

Overall Study: Brodalumab 210 mg

Reporting group description

Participants who received at least 75% of doses with brodalumab 210 mg after the first active dose and no doses of 140 mg during the overall study.

Serious adverse events	Induction Phase: Placebo	Induction Phase: Brodalumab 140 mg	Induction Phase: Brodalumab 210 mg	Overall Study: Brodalumab Variable Dosing	Overall Study: Brodalumab 140 mg	Overall Study: Brodalumab 210 mg
Total subjects affected by serious adverse events
subjects affected / exposed	3 / 220 (1.36%)	6 / 219 (2.74%)	4 / 222 (1.80%)	35 / 179 (19.55%)	11 / 71 (15.49%)	57 / 398 (14.32%)
number of deaths (all causes)	0	0	0	1	0	6
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenolymphoma
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Basal cell carcinoma
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	2 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholesterol granuloma
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lipoma
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal cancer
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Small intestine carcinoma metastatic
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Uterine leiomyoma
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Aortic aneurysm
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Thrombosis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Foetal death
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Cyst
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General physical health deterioration
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyperthermia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oedema peripheral
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sudden death
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Respiratory, thoracic and mediastinal disorders
Apnoea
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Chronic obstructive pulmonary disease
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dyspnoea exertional
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lung perforation
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumothorax spontaneous
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Completed suicide
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Depression
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Suicidal ideation
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Hepatic enzyme increased
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Ankle fracture
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Foot fracture
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intentional overdose
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Limb injury
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lower limb fracture
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Multiple injuries
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Muscle strain
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Patella fracture
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rib fracture
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Road traffic accident
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Scapula fracture
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tendon injury
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Thoracic vertebral fracture
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ulna fracture
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute myocardial infarction
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Angina pectoris
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Arteriospasm coronary
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac arrest
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Myocardial infarction
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	6 / 398 (1.51%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
Nodal arrhythmia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Cerebrovascular accident
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
Headache
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Subarachnoid haemorrhage
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Diplopia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Glaucoma
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Keratopathy
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal adhesions
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal inflammation
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Inflammatory bowel disease
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Inguinal hernia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	1 / 71 (1.41%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intestinal obstruction
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Irritable bowel syndrome
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oesophageal varices haemorrhage
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Pancreatitis acute
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Varices oesophageal
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Volvulus of small bowel
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholecystitis acute
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholelithiasis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatotoxicity
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Psoriasis
subjects affected / exposed	2 / 220 (0.91%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rash
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tubulointerstitial nephritis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urethral stenosis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthritis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Arthropathy
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Back pain
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Femoroacetabular impingement
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Foot deformity
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intervertebral disc protrusion
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	2 / 398 (0.50%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Spinal osteoarthritis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tenosynovitis stenosans
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Abscess of salivary gland
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Anal abscess
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	2 / 179 (1.12%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	1 / 222 (0.45%)	2 / 179 (1.12%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1	1 / 1	1 / 2	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Chronic tonsillitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Coccidioidomycosis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cytomegalovirus infection
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Erysipelas
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Febrile infection
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Kidney infection
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Osteomyelitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pilonidal cyst
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	2 / 179 (1.12%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia streptococcal
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Septic shock
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sinusitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Subcutaneous abscess
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	2 / 179 (1.12%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	2 / 2	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Diabetes mellitus
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Induction Phase: Placebo	Induction Phase: Brodalumab 140 mg	Induction Phase: Brodalumab 210 mg	Overall Study: Brodalumab Variable Dosing	Overall Study: Brodalumab 140 mg	Overall Study: Brodalumab 210 mg
Total subjects affected by non serious adverse events
subjects affected / exposed	111 / 220 (50.45%)	124 / 219 (56.62%)	131 / 222 (59.01%)	160 / 179 (89.39%)	61 / 71 (85.92%)	345 / 398 (86.68%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anogenital warts
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	2 / 179 (1.12%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	2	0	0
Basal cell carcinoma
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	3 / 398 (0.75%)
occurrences all number	0	0	0	0	0	3
Breast neoplasm
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Dysplastic naevus
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Enchondroma
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Fibroma
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	3 / 398 (0.75%)
occurrences all number	0	0	0	0	0	3
Keratoacanthoma
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Lipoma
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	1	0	2	0	0
Melanocytic naevus
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	1	0	2
Neoplasm
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Neurofibroma
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Pyogenic granuloma
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Seborrhoeic keratosis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Skin papilloma
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	6 / 179 (3.35%)	0 / 71 (0.00%)	4 / 398 (1.01%)
occurrences all number	0	0	0	6	0	4
Squamous cell carcinoma of the oral cavity
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	1	0	0	1
Vascular disorders
Aortic aneurysm
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Deep vein thrombosis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Diastolic hypertension
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	1	0	4	0	1
Embolism
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Flushing
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Haematoma
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	4 / 398 (1.01%)
occurrences all number	0	0	1	0	0	4
Hot flush
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Hypertension
subjects affected / exposed	4 / 220 (1.82%)	8 / 219 (3.65%)	2 / 222 (0.90%)	15 / 179 (8.38%)	7 / 71 (9.86%)	23 / 398 (5.78%)
occurrences all number	4	8	2	22	7	26
Hypertensive crisis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Hypotension
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	1	0	1
Lymphoedema
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Neurogenic shock
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	2	0	2	0	0
Orthostatic hypotension
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Peripheral vascular disorder
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Peripheral venous disease
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	1	0	1
Phlebitis superficial
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	1	0	2	0	0
Post thrombotic syndrome
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	1	0	1	0	0
Raynaud's phenomenon
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	1	0	0	1
Systolic hypertension
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Thrombophlebitis superficial
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Varicose vein
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	1	0	1	0	0
Surgical and medical procedures
Abdominal hernia repair
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Arthroscopic surgery
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Bunion operation
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Carpal tunnel decompression
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Cataract operation
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Dental care
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Dental implantation
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Dental operation
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	1	0	1
Dermabrasion
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Endodontic procedure
subjects affected / exposed	2 / 220 (0.91%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	2	0	0	0	0	1
Endometrial ablation
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Internal fixation of spine
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	0	0	0	1	0
Joint surgery
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	1	0	0	1
Knee arthroplasty
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	0	0	0	1	0
Mole excision
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Oophorectomy
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Peripheral nerve operation
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Sinus operation
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	1	0	0	1
Skin lesion excision
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Tooth extraction
subjects affected / exposed	1 / 220 (0.45%)	1 / 219 (0.46%)	1 / 222 (0.45%)	5 / 179 (2.79%)	2 / 71 (2.82%)	5 / 398 (1.26%)
occurrences all number	1	1	1	5	2	5
Tooth repair
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	1	0	0	1	0	0
Vitrectomy
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Wedge resection toenail
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	1	0	1	0	0
Wisdom teeth removal
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	1 / 71 (1.41%)	2 / 398 (0.50%)
occurrences all number	0	0	0	1	1	2
General disorders and administration site conditions
Adverse drug reaction
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Asthenia
subjects affected / exposed	0 / 220 (0.00%)	2 / 219 (0.91%)	1 / 222 (0.45%)	2 / 179 (1.12%)	1 / 71 (1.41%)	3 / 398 (0.75%)
occurrences all number	0	2	1	2	1	4
Chest discomfort
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	1	0	1
Chest pain
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	8 / 398 (2.01%)
occurrences all number	1	0	0	0	0	8
Chills
subjects affected / exposed	1 / 220 (0.45%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	1	1	0	1	0	2
Cyst
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	1	0	0	2
Device failure
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Discomfort
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Fatigue
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	1 / 222 (0.45%)	2 / 179 (1.12%)	1 / 71 (1.41%)	8 / 398 (2.01%)
occurrences all number	0	1	1	2	1	8
Feeling cold
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	2	0	0	0	0	0
Feeling of body temperature change
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	1	0	1	0	0
Gravitational oedema
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Impaired healing
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	0	0	0	1	0
Inflammation
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	1	0	2
Influenza like illness
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	4 / 222 (1.80%)	2 / 179 (1.12%)	0 / 71 (0.00%)	5 / 398 (1.26%)
occurrences all number	1	0	4	2	0	6
Injection site bruising
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Injection site erythema
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	1	0	1	0	0
Injection site extravasation
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Injection site haematoma
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Injection site haemorrhage
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	1	0	0	2
Injection site induration
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Injection site irritation
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Injection site oedema
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	1	0	0	1
Injection site pain
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	3 / 398 (0.75%)
occurrences all number	0	0	1	0	0	3
Injection site reaction
subjects affected / exposed	0 / 220 (0.00%)	2 / 219 (0.91%)	0 / 222 (0.00%)	2 / 179 (1.12%)	2 / 71 (2.82%)	3 / 398 (0.75%)
occurrences all number	0	3	0	2	3	3
Injection site swelling
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Injury associated with device
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Local swelling
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	1 / 71 (1.41%)	1 / 398 (0.25%)
occurrences all number	0	0	0	1	1	1
Malaise
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	3
Metaplasia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Nodule
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Non-cardiac chest pain
subjects affected / exposed	2 / 220 (0.91%)	1 / 219 (0.46%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	2 / 398 (0.50%)
occurrences all number	2	1	0	0	1	4
Oedema
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	1 / 71 (1.41%)	1 / 398 (0.25%)
occurrences all number	0	1	0	1	1	1
Oedema peripheral
subjects affected / exposed	5 / 220 (2.27%)	1 / 219 (0.46%)	1 / 222 (0.45%)	6 / 179 (3.35%)	0 / 71 (0.00%)	8 / 398 (2.01%)
occurrences all number	5	1	1	8	0	8
Pain
subjects affected / exposed	1 / 220 (0.45%)	1 / 219 (0.46%)	0 / 222 (0.00%)	2 / 179 (1.12%)	0 / 71 (0.00%)	3 / 398 (0.75%)
occurrences all number	1	1	0	2	0	3
Peripheral swelling
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	1 / 71 (1.41%)	6 / 398 (1.51%)
occurrences all number	0	0	0	1	1	6
Puncture site reaction
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	2 / 71 (2.82%)	0 / 398 (0.00%)
occurrences all number	0	0	0	0	2	0
Pyrexia
subjects affected / exposed	2 / 220 (0.91%)	3 / 219 (1.37%)	0 / 222 (0.00%)	3 / 179 (1.68%)	2 / 71 (2.82%)	5 / 398 (1.26%)
occurrences all number	2	3	0	3	2	10
Ulcer
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	0	0	0	1	0
Vessel puncture site haematoma
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Xerosis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Immune system disorders
Allergy to arthropod bite
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Drug hypersensitivity
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Flour sensitivity
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Food allergy
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Hypersensitivity
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	1	1
Seasonal allergy
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	3 / 179 (1.68%)	1 / 71 (1.41%)	5 / 398 (1.26%)
occurrences all number	0	0	0	3	1	5
Social circumstances
Dental prosthesis user
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	1	0	1
Reproductive system and breast disorders
Balanoposthitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Benign prostatic hyperplasia
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	0 / 179 (0.00%)	2 / 71 (2.82%)	0 / 398 (0.00%)
occurrences all number	0	1	0	0	2	0
Breast cyst
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Breast mass
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Dysmenorrhoea
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	1 / 179 (0.56%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	1	1	0	2
Erectile dysfunction
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	3 / 398 (0.75%)
occurrences all number	0	0	0	1	0	3
Fibrocystic breast disease
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Haematospermia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	1	0	0	1
Menopausal symptoms
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Menstruation irregular
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	1	1	0	2
Nipple pain
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Ovarian cyst
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	2 / 222 (0.90%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	1	0	3	0	0	4
Prostatitis
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	2 / 179 (1.12%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	1	0	2	0	2
Testicular pain
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	1	0	1	0	0
Uterine cervical erosion
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Vaginal haemorrhage
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Vulvovaginal dryness
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	1	0	0	1
Vulvovaginal pain
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Respiratory, thoracic and mediastinal disorders
Allergic sinusitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Asthma
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	2 / 71 (2.82%)	2 / 398 (0.50%)
occurrences all number	0	0	0	1	2	2
Atelectasis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Bronchial hyperreactivity
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Chronic obstructive pulmonary disease
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	1	0
Cough
subjects affected / exposed	0 / 220 (0.00%)	6 / 219 (2.74%)	3 / 222 (1.35%)	7 / 179 (3.91%)	6 / 71 (8.45%)	21 / 398 (5.28%)
occurrences all number	0	6	3	7	7	23
Dry throat
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Dysphonia
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	2 / 179 (1.12%)	1 / 71 (1.41%)	1 / 398 (0.25%)
occurrences all number	0	1	0	2	1	1
Dyspnoea
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Dyspnoea exertional
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Emphysema
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	1	0	0	0	0	0
Epistaxis
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	2 / 71 (2.82%)	2 / 398 (0.50%)
occurrences all number	0	1	0	1	2	2
Haemothorax
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Lung infiltration
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Nasal congestion
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	2 / 222 (0.90%)	3 / 179 (1.68%)	0 / 71 (0.00%)	8 / 398 (2.01%)
occurrences all number	0	1	2	3	0	9
Nasal dryness
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Nasal inflammation
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Nasal septum deviation
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Oropharyngeal pain
subjects affected / exposed	2 / 220 (0.91%)	4 / 219 (1.83%)	2 / 222 (0.90%)	9 / 179 (5.03%)	2 / 71 (2.82%)	14 / 398 (3.52%)
occurrences all number	3	5	2	10	2	18
Paranasal sinus hypersecretion
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	1	0	0	2
Pharyngeal inflammation
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	3
Pleural effusion
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Productive cough
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	1	0	0	2
Pulmonary arterial hypertension
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Respiratory disorder
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Respiratory tract congestion
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Rhinitis allergic
subjects affected / exposed	1 / 220 (0.45%)	1 / 219 (0.46%)	1 / 222 (0.45%)	5 / 179 (2.79%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	1	1	1	6	0	2
Rhinorrhoea
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	2	1
Sinus congestion
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	2 / 71 (2.82%)	2 / 398 (0.50%)
occurrences all number	1	0	0	1	2	2
Sinusitis noninfective
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	1	1	0	1
Sleep apnoea syndrome
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	1	0	2
Throat irritation
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Upper respiratory tract congestion
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Upper-airway cough syndrome
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Psychiatric disorders
Acute stress disorder
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Agitation
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Anxiety
subjects affected / exposed	1 / 220 (0.45%)	1 / 219 (0.46%)	0 / 222 (0.00%)	8 / 179 (4.47%)	1 / 71 (1.41%)	6 / 398 (1.51%)
occurrences all number	1	1	0	8	1	6
Anxiety disorder
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Apathy
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	1	0	0	0	0	1
Bipolar disorder
subjects affected / exposed	1 / 220 (0.45%)	1 / 219 (0.46%)	0 / 222 (0.00%)	2 / 179 (1.12%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	1	1	0	2	0	0
Depressed mood
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Depression
subjects affected / exposed	1 / 220 (0.45%)	1 / 219 (0.46%)	1 / 222 (0.45%)	7 / 179 (3.91%)	0 / 71 (0.00%)	6 / 398 (1.51%)
occurrences all number	1	1	1	7	0	7
Initial insomnia
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	1	0	1	0	0
Insomnia
subjects affected / exposed	1 / 220 (0.45%)	1 / 219 (0.46%)	0 / 222 (0.00%)	4 / 179 (2.23%)	0 / 71 (0.00%)	7 / 398 (1.76%)
occurrences all number	1	1	0	4	0	7
Libido decreased
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	0	0	0	1	0
Mood altered
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Panic attack
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Sleep disorder
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	2	0	1
Stress
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	3 / 179 (1.68%)	0 / 71 (0.00%)	4 / 398 (1.01%)
occurrences all number	0	1	0	5	0	4
Arthroscopy
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Aspartate aminotransferase increased
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	2 / 179 (1.12%)	1 / 71 (1.41%)	1 / 398 (0.25%)
occurrences all number	0	1	0	3	1	1
Blood bicarbonate decreased
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Blood bilirubin increased
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Blood chloride decreased
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Blood creatinine abnormal
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	0	0	0	1	0
Blood creatinine increased
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	0	0	0	1	0
Blood glucose increased
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	3 / 179 (1.68%)	2 / 71 (2.82%)	3 / 398 (0.75%)
occurrences all number	0	1	0	3	3	3
Blood immunoglobulin E increased
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	1	0	0	0	0	0
Blood pressure diastolic increased
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Blood pressure increased
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	1 / 222 (0.45%)	1 / 179 (0.56%)	1 / 71 (1.41%)	4 / 398 (1.01%)
occurrences all number	1	0	1	1	1	4
Blood sodium decreased
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Blood testosterone decreased
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	2 / 179 (1.12%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	2	0	2
Blood triglycerides increased
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	2 / 179 (1.12%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	2	0	1
Blood uric acid increased
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	3 / 179 (1.68%)	3 / 71 (4.23%)	5 / 398 (1.26%)
occurrences all number	0	1	0	4	6	6
Blood urine present
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
C-reactive protein increased
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	2 / 71 (2.82%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	2	1
Colonoscopy
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Electrocardiogram abnormal
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Endoscopy upper gastrointestinal tract
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Eosinophil count increased
subjects affected / exposed	0 / 220 (0.00%)	2 / 219 (0.91%)	0 / 222 (0.00%)	1 / 179 (0.56%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	2	0	1	1	0
Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Grip strength decreased
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Haemoglobin decreased
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	1	0	0	0	0	0
Hepatic enzyme increased
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	4 / 398 (1.01%)
occurrences all number	0	0	0	0	0	4
Lipids abnormal
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	0	0	0	1	0
Lipids increased
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	1	0	0	0	0	0
Lymph node palpable
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Lymphocyte count decreased
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	0	0	0	1	0
Lymphocyte morphology abnormal
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Neutrophil count decreased
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	1	0	0	2
Neutrophil count increased
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	2 / 179 (1.12%)	2 / 71 (2.82%)	1 / 398 (0.25%)
occurrences all number	0	0	0	2	2	1
Platelet count decreased
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Transaminases increased
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	2 / 222 (0.90%)	0 / 179 (0.00%)	0 / 71 (0.00%)	5 / 398 (1.26%)
occurrences all number	1	0	2	0	0	9
Urine analysis abnormal
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Weight decreased
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	1 / 71 (1.41%)	3 / 398 (0.75%)
occurrences all number	0	0	1	0	1	3
Weight increased
subjects affected / exposed	0 / 220 (0.00%)	2 / 219 (0.91%)	0 / 222 (0.00%)	3 / 179 (1.68%)	1 / 71 (1.41%)	6 / 398 (1.51%)
occurrences all number	0	2	0	3	1	10
White blood cell count increased
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	2 / 179 (1.12%)	2 / 71 (2.82%)	2 / 398 (0.50%)
occurrences all number	0	0	0	2	2	2
White blood cells urine positive
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Wound healing normal
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Injury, poisoning and procedural complications
Abdominal injury
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Animal bite
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	4 / 398 (1.01%)
occurrences all number	0	0	1	0	0	4
Ankle fracture
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	1	0	1
Arthropod bite
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	3 / 179 (1.68%)	1 / 71 (1.41%)	6 / 398 (1.51%)
occurrences all number	0	0	0	3	1	6
Arthropod sting
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	1	0
Burns second degree
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Cartilage injury
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	0	0	0	1	0
Chemical injury
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	1	1	0	1
Concussion
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	1	0	1	0	2
Contusion
subjects affected / exposed	2 / 220 (0.91%)	0 / 219 (0.00%)	1 / 222 (0.45%)	3 / 179 (1.68%)	0 / 71 (0.00%)	9 / 398 (2.26%)
occurrences all number	2	0	1	3	0	9
Dislocation of vertebra
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Epicondylitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Eye injury
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Fall
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	7 / 179 (3.91%)	1 / 71 (1.41%)	5 / 398 (1.26%)
occurrences all number	0	1	0	9	1	5
Foot fracture
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	3 / 179 (1.68%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	0	0	3	1	0
Gingival injury
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Hand fracture
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	1	0	0	0	0	0
Heat stroke
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Joint injury
subjects affected / exposed	2 / 220 (0.91%)	0 / 219 (0.00%)	1 / 222 (0.45%)	1 / 179 (0.56%)	1 / 71 (1.41%)	7 / 398 (1.76%)
occurrences all number	2	0	1	1	1	7
Laceration
subjects affected / exposed	1 / 220 (0.45%)	1 / 219 (0.46%)	0 / 222 (0.00%)	2 / 179 (1.12%)	1 / 71 (1.41%)	9 / 398 (2.26%)
occurrences all number	1	1	0	2	1	11
Ligament injury
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Ligament rupture
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Ligament sprain
subjects affected / exposed	1 / 220 (0.45%)	3 / 219 (1.37%)	0 / 222 (0.00%)	5 / 179 (2.79%)	3 / 71 (4.23%)	7 / 398 (1.76%)
occurrences all number	1	3	0	5	3	8
Limb injury
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	2 / 179 (1.12%)	0 / 71 (0.00%)	3 / 398 (0.75%)
occurrences all number	0	0	0	2	0	3
Meniscus injury
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	6 / 398 (1.51%)
occurrences all number	0	0	0	0	0	6
Muscle injury
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Muscle rupture
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	1	0	1	0	0
Muscle strain
subjects affected / exposed	2 / 220 (0.91%)	0 / 219 (0.00%)	1 / 222 (0.45%)	3 / 179 (1.68%)	1 / 71 (1.41%)	11 / 398 (2.76%)
occurrences all number	2	0	1	3	1	13
Nail avulsion
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	2	0	0
Nail injury
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Neck injury
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	1	0	0	1
Post procedural inflammation
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	2
Post-traumatic neck syndrome
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	1	0	1
Post-traumatic pain
subjects affected / exposed	2 / 220 (0.91%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	2	0	0	0	0	1
Postoperative wound complication
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Procedural pain
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	2 / 179 (1.12%)	0 / 71 (0.00%)	6 / 398 (1.51%)
occurrences all number	0	0	1	2	0	6
Procedural site reaction
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Radius fracture
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Rib fracture
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	1 / 71 (1.41%)	3 / 398 (0.75%)
occurrences all number	0	0	0	2	1	3
Road traffic accident
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	1 / 71 (1.41%)	1 / 398 (0.25%)
occurrences all number	0	0	1	0	1	1
Skeletal injury
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Skin abrasion
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	2 / 71 (2.82%)	2 / 398 (0.50%)
occurrences all number	0	1	0	4	2	2
Skin injury
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	0	0	0	1	0
Soft tissue injury
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	4 / 398 (1.01%)
occurrences all number	0	0	1	0	0	4
Sunburn
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	1	0	0	1	1	0
Synovial rupture
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Tendon injury
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	1	0	1
Tendon rupture
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	1	0	1
Thermal burn
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	1	1
Tibia fracture
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Tooth fracture
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	1 / 222 (0.45%)	3 / 179 (1.68%)	0 / 71 (0.00%)	6 / 398 (1.51%)
occurrences all number	1	0	2	3	0	7
Traumatic haematoma
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	0	0	0	1	0
Ulnar nerve injury
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Upper limb fracture
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Wound
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	2 / 179 (1.12%)	1 / 71 (1.41%)	1 / 398 (0.25%)
occurrences all number	0	1	0	2	1	1
Wrist fracture
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Cardiac disorders
Angina pectoris
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Arrhythmia
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	1 / 398 (0.25%)
occurrences all number	0	1	0	0	1	1
Atrial hypertrophy
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Atrioventricular block first degree
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	2 / 179 (1.12%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	2	0	1
Bradycardia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Bundle branch block left
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Cardiac failure congestive
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Cardiomegaly
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	1	0	1
Coronary artery disease
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Hypertensive heart disease
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Ischaemic cardiomyopathy
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Left ventricular hypertrophy
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Myocardial ischaemia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	0	0	0	1	0
Palpitations
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	1	0	2
Sinus arrhythmia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Sinus tachycardia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Tachycardia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	5 / 398 (1.26%)
occurrences all number	0	0	0	1	0	5
Ventricular extrasystoles
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	0	0	0	1	0
Nervous system disorders
Ageusia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Amnesia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	2	1
Burning sensation
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	1	0	0	2
Carpal tunnel syndrome
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	2 / 179 (1.12%)	1 / 71 (1.41%)	2 / 398 (0.50%)
occurrences all number	0	0	0	2	1	3
Cerebral cyst
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Cerebral ischaemia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Demyelination
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	0	0	0	1	0
Diabetic neuropathy
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	1	1
Dizziness
subjects affected / exposed	0 / 220 (0.00%)	3 / 219 (1.37%)	0 / 222 (0.00%)	3 / 179 (1.68%)	1 / 71 (1.41%)	7 / 398 (1.76%)
occurrences all number	0	3	0	6	1	7
Dizziness postural
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	0	0	0	1	0
Epilepsy
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Formication
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Headache
subjects affected / exposed	7 / 220 (3.18%)	12 / 219 (5.48%)	12 / 222 (5.41%)	17 / 179 (9.50%)	5 / 71 (7.04%)	32 / 398 (8.04%)
occurrences all number	7	15	15	39	5	60
Hypoaesthesia
subjects affected / exposed	1 / 220 (0.45%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	1 / 71 (1.41%)	3 / 398 (0.75%)
occurrences all number	1	1	0	1	1	4
Hypotonia
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	1	0	0	0	0	0
Intercostal neuralgia
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	1	0	1	0	1
Migraine
subjects affected / exposed	0 / 220 (0.00%)	2 / 219 (0.91%)	1 / 222 (0.45%)	2 / 179 (1.12%)	1 / 71 (1.41%)	5 / 398 (1.26%)
occurrences all number	0	2	1	2	1	5
Morton's neuralgia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Nerve compression
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Neuropathy peripheral
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Occipital neuralgia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Paraesthesia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Polyneuropathy
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Presyncope
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	1 / 222 (0.45%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	1	1	1	0	1
Restless legs syndrome
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Sciatica
subjects affected / exposed	1 / 220 (0.45%)	1 / 219 (0.46%)	1 / 222 (0.45%)	2 / 179 (1.12%)	1 / 71 (1.41%)	7 / 398 (1.76%)
occurrences all number	1	2	1	2	2	8
Sinus headache
subjects affected / exposed	2 / 220 (0.91%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	2	0	0	0	0	0
Somnolence
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	0	0	0	1	0
Syncope
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	5 / 398 (1.26%)
occurrences all number	0	0	0	0	0	5
Tension headache
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Tongue biting
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Transient ischaemic attack
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Tremor
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	2 / 71 (2.82%)	0 / 398 (0.00%)
occurrences all number	1	0	0	0	3	0
Eosinophilia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Iron deficiency anaemia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	1	0	1
Leukocytosis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Leukopenia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Lymphadenopathy
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Lymphopenia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	1	0	1
Neutropenia
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	1	0	1	0	1
Neutrophilia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	3 / 398 (0.75%)
occurrences all number	0	0	0	1	0	3
Normochromic normocytic anaemia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Pancytopenia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Sickle cell anaemia with crisis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Thrombocytopenia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	1	0	0	1
Ear and labyrinth disorders
Cerumen impaction
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Deafness
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Ear discomfort
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Ear pain
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	3 / 179 (1.68%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	1	0	3	0	1
Inner ear inflammation
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	0	0	0	1	0
Otorrhoea
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Tinnitus
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Vertigo
subjects affected / exposed	2 / 220 (0.91%)	0 / 219 (0.00%)	0 / 222 (0.00%)	2 / 179 (1.12%)	0 / 71 (0.00%)	6 / 398 (1.51%)
occurrences all number	3	0	0	3	0	6
Vertigo positional
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	1	0	2	0	0
Eye disorders
Age-related macular degeneration
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Asthenopia
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	1	0	1	0	0
Blepharitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Cataract
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	1	0	0	1	0	1
Chalazion
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	1	0	1	0	0
Conjunctival haemorrhage
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Conjunctival hyperaemia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Dry eye
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	5 / 398 (1.26%)
occurrences all number	0	1	0	1	0	5
Eczema eyelids
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Eye discharge
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Eye movement disorder
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	0	0	0	1	0
Eye pain
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Eye pruritus
subjects affected / exposed	0 / 220 (0.00%)	2 / 219 (0.91%)	0 / 222 (0.00%)	2 / 179 (1.12%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	2	0	2	0	0
Eye swelling
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Glaucoma
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	0	0	0	1	0
Iritis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	1	0	0	2
Lacrimation increased
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Macular degeneration
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Ocular hyperaemia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	3 / 398 (0.75%)
occurrences all number	0	0	0	0	0	3
Photopsia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	1	0	0	1
Retinal haemorrhage
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Retinal telangiectasia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Uveitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	3
Vision blurred
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	1	0	1	1	0
Visual acuity reduced
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	1	0	0	1	0
Vitreous floaters
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Gastrointestinal disorders
Abdominal discomfort
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	1	0	0	1	0	0
Abdominal distension
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Abdominal pain
subjects affected / exposed	2 / 220 (0.91%)	1 / 219 (0.46%)	0 / 222 (0.00%)	2 / 179 (1.12%)	1 / 71 (1.41%)	8 / 398 (2.01%)
occurrences all number	2	1	0	2	1	8
Abdominal pain lower
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	1	0	0	0	0	1
Abdominal pain upper
subjects affected / exposed	1 / 220 (0.45%)	1 / 219 (0.46%)	2 / 222 (0.90%)	2 / 179 (1.12%)	0 / 71 (0.00%)	11 / 398 (2.76%)
occurrences all number	1	1	3	2	0	12
Abdominal tenderness
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	1	0	0	1	0
Abnormal faeces
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Anal fissure
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Aphthous stomatitis
subjects affected / exposed	1 / 220 (0.45%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	1	1	0	1	1	0
Cheilitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	1 / 71 (1.41%)	3 / 398 (0.75%)
occurrences all number	0	0	0	1	1	3
Chronic gastritis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Constipation
subjects affected / exposed	0 / 220 (0.00%)	2 / 219 (0.91%)	0 / 222 (0.00%)	3 / 179 (1.68%)	2 / 71 (2.82%)	4 / 398 (1.01%)
occurrences all number	0	2	0	3	2	4
Dental caries
subjects affected / exposed	2 / 220 (0.91%)	1 / 219 (0.46%)	0 / 222 (0.00%)	3 / 179 (1.68%)	0 / 71 (0.00%)	3 / 398 (0.75%)
occurrences all number	2	1	0	4	0	4
Diarrhoea
subjects affected / exposed	1 / 220 (0.45%)	4 / 219 (1.83%)	4 / 222 (1.80%)	9 / 179 (5.03%)	2 / 71 (2.82%)	23 / 398 (5.78%)
occurrences all number	2	4	5	11	2	35
Diarrhoea haemorrhagic
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	3	0	0
Diverticulum intestinal
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Dry mouth
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	1 / 222 (0.45%)	1 / 179 (0.56%)	1 / 71 (1.41%)	3 / 398 (0.75%)
occurrences all number	0	2	1	2	1	3
Duodenitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Dyspepsia
subjects affected / exposed	0 / 220 (0.00%)	2 / 219 (0.91%)	1 / 222 (0.45%)	5 / 179 (2.79%)	2 / 71 (2.82%)	10 / 398 (2.51%)
occurrences all number	0	2	1	5	2	14
Dysphagia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	0	0	0	1	0
Epigastric discomfort
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	2
Eructation
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	1	0	0	1
Flatulence
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	1	0	0	1	0
Food poisoning
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	0 / 222 (0.00%)	2 / 179 (1.12%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	1	0	0	2	0	0
Gastric ulcer
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Gastritis
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	2 / 179 (1.12%)	0 / 71 (0.00%)	3 / 398 (0.75%)
occurrences all number	0	1	0	2	0	3
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	3 / 179 (1.68%)	0 / 71 (0.00%)	12 / 398 (3.02%)
occurrences all number	0	0	0	3	0	12
Gingival cyst
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Glossodynia
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	1	0	0	0	0	0
Haematochezia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Haemorrhoids
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	3 / 398 (0.75%)
occurrences all number	0	0	1	0	0	3
Hiatus hernia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Hyperchlorhydria
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Inflammatory bowel disease
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	1	0	0	0	0	0
Inguinal hernia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	1	0	1
Irritable bowel syndrome
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Large intestine polyp
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Lip blister
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	1	0	1	0	0
Lip dry
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	1	0	1	0	0
Lip pain
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	2
Lip swelling
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Mouth swelling
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Nausea
subjects affected / exposed	2 / 220 (0.91%)	5 / 219 (2.28%)	5 / 222 (2.25%)	7 / 179 (3.91%)	2 / 71 (2.82%)	13 / 398 (3.27%)
occurrences all number	2	6	14	8	2	25
Noninfective gingivitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Oesophageal obstruction
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	0	0	0	1	0
Oesophageal spasm
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Oesophagitis
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	1	0	0	0	0	1
Parotid gland enlargement
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Plicated tongue
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Poor dental condition
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Rectal haemorrhage
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Salivary duct inflammation
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	1	0	1	0	0
Sensitivity of teeth
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Stomatitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Tongue blistering
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Tooth disorder
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	1	0	0	0	0	2
Toothache
subjects affected / exposed	2 / 220 (0.91%)	2 / 219 (0.91%)	0 / 222 (0.00%)	4 / 179 (2.23%)	1 / 71 (1.41%)	15 / 398 (3.77%)
occurrences all number	3	2	0	5	1	18
Umbilical hernia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Vomiting
subjects affected / exposed	1 / 220 (0.45%)	4 / 219 (1.83%)	2 / 222 (0.90%)	6 / 179 (3.35%)	1 / 71 (1.41%)	7 / 398 (1.76%)
occurrences all number	1	4	2	7	1	7
Hepatobiliary disorders
Biliary colic
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	1	0	0	1	0
Cholecystitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Cholelithiasis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	1	0	2
Gallbladder polyp
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Hepatic steatosis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Hyperbilirubinaemia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	1	0	1
Non-alcoholic steatohepatitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	2 / 179 (1.12%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	2	0	0
Portal hypertension
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Skin and subcutaneous tissue disorders
Acne
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	1	0
Actinic keratosis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	1 / 71 (1.41%)	1 / 398 (0.25%)
occurrences all number	0	0	0	1	1	3
Alopecia
subjects affected / exposed	0 / 220 (0.00%)	2 / 219 (0.91%)	1 / 222 (0.45%)	3 / 179 (1.68%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	2	1	4	0	2
Alopecia areata
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	1	0	0	1
Angioedema
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Angiokeratoma
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Decubitus ulcer
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Dermal cyst
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	1	0	1
Dermatitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	3 / 179 (1.68%)	1 / 71 (1.41%)	3 / 398 (0.75%)
occurrences all number	0	0	0	4	1	3
Dermatitis acneiform
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Dermatitis allergic
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Dermatitis contact
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	4 / 179 (2.23%)	1 / 71 (1.41%)	8 / 398 (2.01%)
occurrences all number	0	0	0	5	2	10
Diffuse alopecia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Dry skin
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	1 / 222 (0.45%)	1 / 179 (0.56%)	0 / 71 (0.00%)	3 / 398 (0.75%)
occurrences all number	0	2	1	2	0	3
Dyshidrotic eczema
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	2 / 179 (1.12%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	1	2	0	2
Ecchymosis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	3 / 398 (0.75%)
occurrences all number	0	0	0	0	0	3
Eczema
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	2 / 179 (1.12%)	0 / 71 (0.00%)	10 / 398 (2.51%)
occurrences all number	0	0	1	2	0	10
Eczema asteatotic
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Erythema
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	4 / 398 (1.01%)
occurrences all number	0	0	1	0	0	4
Guttate psoriasis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Hand dermatitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	1	0	2
Hidradenitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Hyperhidrosis
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	1	0	1	0	2
Hyperkeratosis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	1	0	0	2
Intertrigo
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	2 / 179 (1.12%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	2	0	0
Lichen planus
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Lichenification
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	1	0	0	1
Nail psoriasis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Neurodermatitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Onycholysis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Palmar-plantar erythrodysaesthesia syndrome
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Papule
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Photosensitivity reaction
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Pityriasis rosea
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Polymorphic light eruption
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Prurigo
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	1	0	1	0	1
Pruritus
subjects affected / exposed	5 / 220 (2.27%)	5 / 219 (2.28%)	5 / 222 (2.25%)	8 / 179 (4.47%)	2 / 71 (2.82%)	16 / 398 (4.02%)
occurrences all number	6	5	6	9	6	23
Pruritus generalised
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	1 / 222 (0.45%)	1 / 179 (0.56%)	1 / 71 (1.41%)	2 / 398 (0.50%)
occurrences all number	0	2	1	1	2	2
Psoriasis
subjects affected / exposed	3 / 220 (1.36%)	2 / 219 (0.91%)	1 / 222 (0.45%)	9 / 179 (5.03%)	1 / 71 (1.41%)	6 / 398 (1.51%)
occurrences all number	4	2	2	10	1	8
Pustular psoriasis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	2 / 222 (0.90%)	3 / 179 (1.68%)	1 / 71 (1.41%)	2 / 398 (0.50%)
occurrences all number	0	0	2	5	1	2
Rash
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	4 / 222 (1.80%)	4 / 179 (2.23%)	0 / 71 (0.00%)	9 / 398 (2.26%)
occurrences all number	0	0	5	4	0	11
Rash pruritic
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Rebound psoriasis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Rosacea
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	1	0	1
Scab
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Seborrhoeic dermatitis
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	3 / 179 (1.68%)	3 / 71 (4.23%)	5 / 398 (1.26%)
occurrences all number	0	1	0	3	4	5
Skin discomfort
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Skin exfoliation
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	1	0	1	0	0
Skin fissures
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	3 / 398 (0.75%)
occurrences all number	0	0	0	0	0	3
Skin hyperpigmentation
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	1	0	0	1
Skin mass
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	1 / 71 (1.41%)	1 / 398 (0.25%)
occurrences all number	0	0	1	0	1	3
Skin odour abnormal
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Stasis dermatitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Swelling face
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Urticaria
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	3 / 179 (1.68%)	1 / 71 (1.41%)	4 / 398 (1.01%)
occurrences all number	0	0	1	3	1	4
Vitiligo
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	1	0
Renal and urinary disorders
Dysuria
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	2 / 179 (1.12%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	1	0	3	0	1
Glycosuria
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	1	0	1	0	0
Haematuria
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	3 / 179 (1.68%)	0 / 71 (0.00%)	4 / 398 (1.01%)
occurrences all number	0	0	1	3	0	5
Hydronephrosis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	0	0	0	1	0
Leukocyturia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Micturition frequency decreased
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	1	0	0	1	0
Nephrolithiasis
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	1 / 71 (1.41%)	10 / 398 (2.51%)
occurrences all number	1	0	0	1	1	11
Pollakiuria
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Proteinuria
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	4 / 398 (1.01%)
occurrences all number	0	1	0	1	0	5
Renal colic
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	1	0	2
Renal cyst
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Ureterocele
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Urinary tract inflammation
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Endocrine disorders
Goitre
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	1	0	0	2
Hyperthyroidism
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	2
Hypogonadism
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	1	0	0	0	0	0
Hypothyroidism
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Thyroid cyst
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	1	0	0	0	0	0
Musculoskeletal and connective tissue disorders
Ankylosing spondylitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	1	0	0	1
Arthralgia
subjects affected / exposed	6 / 220 (2.73%)	11 / 219 (5.02%)	7 / 222 (3.15%)	26 / 179 (14.53%)	7 / 71 (9.86%)	50 / 398 (12.56%)
occurrences all number	7	12	8	35	8	63
Arthritis
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	2 / 222 (0.90%)	2 / 179 (1.12%)	1 / 71 (1.41%)	15 / 398 (3.77%)
occurrences all number	0	1	2	2	1	15
Arthropathy
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Back pain
subjects affected / exposed	4 / 220 (1.82%)	2 / 219 (0.91%)	5 / 222 (2.25%)	11 / 179 (6.15%)	4 / 71 (5.63%)	36 / 398 (9.05%)
occurrences all number	4	2	5	12	4	41
Bone pain
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	2	0	0	2
Bursitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	2 / 179 (1.12%)	0 / 71 (0.00%)	3 / 398 (0.75%)
occurrences all number	0	0	0	2	0	3
Chondromalacia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Costochondritis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Dactylitis
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	1 / 222 (0.45%)	2 / 179 (1.12%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	1	0	1	2	0	1
Dupuytren's contracture
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Exostosis
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	1	0	0	1	0
Fibromyalgia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	2 / 179 (1.12%)	1 / 71 (1.41%)	1 / 398 (0.25%)
occurrences all number	0	0	0	2	1	1
Flank pain
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Groin pain
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	2 / 222 (0.90%)	1 / 179 (0.56%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	2	1	0	2
Intervertebral disc degeneration
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Intervertebral disc disorder
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	1	0	0	0	0	1
Intervertebral disc protrusion
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	1	3
Joint effusion
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Joint stiffness
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	1	0	1
Joint swelling
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	1 / 71 (1.41%)	1 / 398 (0.25%)
occurrences all number	0	0	0	1	1	1
Metatarsalgia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Muscle spasms
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	2 / 179 (1.12%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	1	0	2	0	2
Muscle tightness
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	2 / 179 (1.12%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	2	0	0
Muscle twitching
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Muscular weakness
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Musculoskeletal chest pain
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Musculoskeletal pain
subjects affected / exposed	2 / 220 (0.91%)	1 / 219 (0.46%)	3 / 222 (1.35%)	2 / 179 (1.12%)	0 / 71 (0.00%)	11 / 398 (2.76%)
occurrences all number	3	1	3	2	0	11
Musculoskeletal stiffness
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Myalgia
subjects affected / exposed	0 / 220 (0.00%)	2 / 219 (0.91%)	4 / 222 (1.80%)	3 / 179 (1.68%)	1 / 71 (1.41%)	10 / 398 (2.51%)
occurrences all number	0	2	5	3	1	13
Neck pain
subjects affected / exposed	1 / 220 (0.45%)	1 / 219 (0.46%)	0 / 222 (0.00%)	2 / 179 (1.12%)	0 / 71 (0.00%)	6 / 398 (1.51%)
occurrences all number	1	1	0	2	0	7
Osteoarthritis
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	3 / 71 (4.23%)	12 / 398 (3.02%)
occurrences all number	1	0	0	0	3	12
Pain in extremity
subjects affected / exposed	2 / 220 (0.91%)	1 / 219 (0.46%)	4 / 222 (1.80%)	7 / 179 (3.91%)	1 / 71 (1.41%)	10 / 398 (2.51%)
occurrences all number	2	1	6	8	3	12
Pain in jaw
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	1	0	1
Patellofemoral pain syndrome
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Periarthritis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Plantar fasciitis
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	1	0	1	0	1
Polyarthritis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	4
Polymyalgia rheumatica
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Psoriatic arthropathy
subjects affected / exposed	4 / 220 (1.82%)	3 / 219 (1.37%)	4 / 222 (1.80%)	6 / 179 (3.35%)	3 / 71 (4.23%)	15 / 398 (3.77%)
occurrences all number	4	3	5	10	3	19
Rhabdomyolysis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Rheumatoid arthritis
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	1	0	0	0	0	0
Rotator cuff syndrome
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	1 / 222 (0.45%)	1 / 179 (0.56%)	1 / 71 (1.41%)	5 / 398 (1.26%)
occurrences all number	0	1	1	1	1	5
Spinal column stenosis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	1	1	0	0
Spinal osteoarthritis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	1	2
Spinal pain
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	2 / 222 (0.90%)	0 / 179 (0.00%)	1 / 71 (1.41%)	5 / 398 (1.26%)
occurrences all number	0	0	2	0	1	6
Synovial cyst
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	3 / 398 (0.75%)
occurrences all number	0	0	0	0	0	3
Synovitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Temporomandibular joint syndrome
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Tendon pain
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Tendonitis
subjects affected / exposed	1 / 220 (0.45%)	1 / 219 (0.46%)	2 / 222 (0.90%)	3 / 179 (1.68%)	0 / 71 (0.00%)	11 / 398 (2.76%)
occurrences all number	1	1	2	3	0	12
Tenosynovitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	1	0	1
Torticollis
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	1	0	0	1	0
Infections and infestations
Abdominal abscess
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	1	0	0	1	0
Abscess
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	1	0	2
Abscess limb
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	1	0	0	1
Acarodermatitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Acne pustular
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	1	0	0	2
Acute sinusitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	3 / 398 (0.75%)
occurrences all number	0	0	0	0	0	3
Acute tonsillitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Appendicitis
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	1	0	1	0	0
Bacteriuria
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Balanitis candida
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Body tinea
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Bronchitis
subjects affected / exposed	3 / 220 (1.36%)	3 / 219 (1.37%)	3 / 222 (1.35%)	9 / 179 (5.03%)	6 / 71 (8.45%)	25 / 398 (6.28%)
occurrences all number	3	3	3	12	8	33
Bronchitis bacterial
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	1	0	1
Bronchitis viral
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Candida infection
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	3
Cellulitis
subjects affected / exposed	1 / 220 (0.45%)	1 / 219 (0.46%)	1 / 222 (0.45%)	4 / 179 (2.23%)	1 / 71 (1.41%)	9 / 398 (2.26%)
occurrences all number	1	1	1	4	1	10
Chlamydial infection
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Chronic tonsillitis
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	1	0	1	0	0
Conjunctivitis
subjects affected / exposed	0 / 220 (0.00%)	2 / 219 (0.91%)	5 / 222 (2.25%)	6 / 179 (3.35%)	3 / 71 (4.23%)	11 / 398 (2.76%)
occurrences all number	0	2	5	6	3	14
Conjunctivitis bacterial
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Corneal infection
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Cystitis
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	1 / 222 (0.45%)	4 / 179 (2.23%)	0 / 71 (0.00%)	7 / 398 (1.76%)
occurrences all number	1	0	1	4	0	8
Cystitis bacterial
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	1	0	0	1
Dacryocanaliculitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Dermo-hypodermitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Diarrhoea infectious
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	1	0	2
Diverticulitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Ear infection
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	5 / 179 (2.79%)	3 / 71 (4.23%)	6 / 398 (1.51%)
occurrences all number	0	1	0	5	3	9
Eczema infected
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Enteritis infectious
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Erysipelas
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
External ear cellulitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	2 / 179 (1.12%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	2	0	0
Eye infection
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Folliculitis
subjects affected / exposed	1 / 220 (0.45%)	2 / 219 (0.91%)	1 / 222 (0.45%)	5 / 179 (2.79%)	1 / 71 (1.41%)	7 / 398 (1.76%)
occurrences all number	1	2	1	5	1	10
Fungal infection
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	2 / 179 (1.12%)	0 / 71 (0.00%)	3 / 398 (0.75%)
occurrences all number	0	0	0	2	0	4
Fungal skin infection
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	1	0	0	2
Furuncle
subjects affected / exposed	1 / 220 (0.45%)	1 / 219 (0.46%)	0 / 222 (0.00%)	2 / 179 (1.12%)	0 / 71 (0.00%)	3 / 398 (0.75%)
occurrences all number	1	1	0	3	0	3
Gastroenteritis
subjects affected / exposed	3 / 220 (1.36%)	0 / 219 (0.00%)	3 / 222 (1.35%)	7 / 179 (3.91%)	1 / 71 (1.41%)	16 / 398 (4.02%)
occurrences all number	4	0	3	7	1	20
Gastroenteritis viral
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	8 / 398 (2.01%)
occurrences all number	0	1	0	1	0	10
Gastrointestinal infection
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	1 / 71 (1.41%)	1 / 398 (0.25%)
occurrences all number	0	1	0	1	1	1
Gastrointestinal viral infection
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Genital herpes
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	2 / 222 (0.90%)	2 / 179 (1.12%)	0 / 71 (0.00%)	4 / 398 (1.01%)
occurrences all number	0	0	2	3	0	4
Gingivitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	1	0
Helicobacter infection
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Herpes oesophagitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Herpes simplex
subjects affected / exposed	1 / 220 (0.45%)	2 / 219 (0.91%)	0 / 222 (0.00%)	1 / 179 (0.56%)	1 / 71 (1.41%)	2 / 398 (0.50%)
occurrences all number	1	2	0	2	1	2
Herpes virus infection
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	1	0	4	0	1
Herpes zoster
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	1 / 71 (1.41%)	2 / 398 (0.50%)
occurrences all number	1	0	0	1	1	2
Hordeolum
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	6 / 398 (1.51%)
occurrences all number	0	0	0	0	0	6
Impetigo
subjects affected / exposed	1 / 220 (0.45%)	1 / 219 (0.46%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	1 / 398 (0.25%)
occurrences all number	1	1	0	0	1	2
Influenza
subjects affected / exposed	1 / 220 (0.45%)	1 / 219 (0.46%)	4 / 222 (1.80%)	9 / 179 (5.03%)	2 / 71 (2.82%)	16 / 398 (4.02%)
occurrences all number	1	1	4	11	2	19
Labyrinthitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Laryngitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	2 / 179 (1.12%)	0 / 71 (0.00%)	4 / 398 (1.01%)
occurrences all number	0	0	0	2	0	4
Localised infection
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	1	0	1
Mucosal infection
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Nasopharyngitis
subjects affected / exposed	22 / 220 (10.00%)	20 / 219 (9.13%)	22 / 222 (9.91%)	38 / 179 (21.23%)	15 / 71 (21.13%)	81 / 398 (20.35%)
occurrences all number	24	21	27	66	21	150
Oesophageal candidiasis
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	1	0	1	0	0
Omphalitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Onychomycosis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	1	0	1
Oral candidiasis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	3 / 179 (1.68%)	1 / 71 (1.41%)	16 / 398 (4.02%)
occurrences all number	0	0	0	3	1	17
Oral fungal infection
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	3 / 398 (0.75%)
occurrences all number	0	0	0	1	0	4
Oral herpes
subjects affected / exposed	0 / 220 (0.00%)	2 / 219 (0.91%)	0 / 222 (0.00%)	4 / 179 (2.23%)	0 / 71 (0.00%)	7 / 398 (1.76%)
occurrences all number	0	2	0	5	0	16
Oral infection
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Orchitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Oropharyngeal candidiasis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	0	0	0	1	0
Oropharyngitis fungal
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Osteomyelitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Otitis externa
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	2 / 222 (0.90%)	0 / 179 (0.00%)	0 / 71 (0.00%)	6 / 398 (1.51%)
occurrences all number	0	0	2	0	0	9
Otitis media
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	7 / 398 (1.76%)
occurrences all number	1	0	1	0	0	9
Otitis media acute
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Papilloma viral infection
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Paronychia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	0 / 179 (0.00%)	0 / 71 (0.00%)	4 / 398 (1.01%)
occurrences all number	0	0	1	0	0	4
Pericarditis infective
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Periodontitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	2 / 179 (1.12%)	1 / 71 (1.41%)	1 / 398 (0.25%)
occurrences all number	0	0	0	2	2	1
Peritonsillar abscess
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	0	0	0	1	0
Pharyngitis
subjects affected / exposed	2 / 220 (0.91%)	3 / 219 (1.37%)	3 / 222 (1.35%)	13 / 179 (7.26%)	4 / 71 (5.63%)	24 / 398 (6.03%)
occurrences all number	2	3	3	13	6	31
Pharyngitis bacterial
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	2 / 222 (0.90%)	1 / 179 (0.56%)	1 / 71 (1.41%)	5 / 398 (1.26%)
occurrences all number	0	0	2	1	1	6
Pharyngitis streptococcal
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	4 / 398 (1.01%)
occurrences all number	0	0	0	1	0	4
Pharyngotonsillitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Pilonidal cyst
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	1	0	1
Pneumonia
subjects affected / exposed	1 / 220 (0.45%)	1 / 219 (0.46%)	0 / 222 (0.00%)	1 / 179 (0.56%)	2 / 71 (2.82%)	5 / 398 (1.26%)
occurrences all number	1	1	0	1	2	5
Post procedural infection
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Pulpitis dental
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	1 / 222 (0.45%)	1 / 179 (0.56%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	1	1	1	0	2
Pyelonephritis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	2	0	0
Pyuria
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Rash pustular
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	1	2
Respiratory tract infection
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	1	0	0	0	0	0
Respiratory tract infection viral
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Rhinitis
subjects affected / exposed	2 / 220 (0.91%)	2 / 219 (0.91%)	5 / 222 (2.25%)	2 / 179 (1.12%)	0 / 71 (0.00%)	14 / 398 (3.52%)
occurrences all number	2	2	5	2	0	16
Sinusitis
subjects affected / exposed	4 / 220 (1.82%)	2 / 219 (0.91%)	4 / 222 (1.80%)	11 / 179 (6.15%)	4 / 71 (5.63%)	27 / 398 (6.78%)
occurrences all number	4	2	4	15	4	37
Skin bacterial infection
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Skin candida
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	1	0	0	0	0	0
Skin infection
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Staphylococcal infection
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	0	0	2
Staphylococcal skin infection
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Subcutaneous abscess
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	2 / 179 (1.12%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	2	0	0
Tinea cruris
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	2
Tinea infection
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Tinea manuum
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	0	0	0	1	0
Tinea pedis
subjects affected / exposed	0 / 220 (0.00%)	2 / 219 (0.91%)	2 / 222 (0.90%)	4 / 179 (2.23%)	2 / 71 (2.82%)	8 / 398 (2.01%)
occurrences all number	0	2	2	4	2	11
Tonsillitis
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	1 / 222 (0.45%)	2 / 179 (1.12%)	0 / 71 (0.00%)	4 / 398 (1.01%)
occurrences all number	0	1	2	3	0	8
Tooth abscess
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	1 / 222 (0.45%)	1 / 179 (0.56%)	1 / 71 (1.41%)	8 / 398 (2.01%)
occurrences all number	0	1	1	1	1	8
Tooth infection
subjects affected / exposed	2 / 220 (0.91%)	6 / 219 (2.74%)	1 / 222 (0.45%)	10 / 179 (5.59%)	3 / 71 (4.23%)	8 / 398 (2.01%)
occurrences all number	2	6	1	11	3	8
Toxocariasis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Tracheitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	2 / 179 (1.12%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	2	0	0
Upper respiratory tract infection
subjects affected / exposed	14 / 220 (6.36%)	18 / 219 (8.22%)	18 / 222 (8.11%)	36 / 179 (20.11%)	12 / 71 (16.90%)	81 / 398 (20.35%)
occurrences all number	18	20	21	61	23	133
Upper respiratory tract infection bacterial
subjects affected / exposed	1 / 220 (0.45%)	1 / 219 (0.46%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	2 / 398 (0.50%)
occurrences all number	1	1	0	0	1	2
Urinary tract infection
subjects affected / exposed	0 / 220 (0.00%)	3 / 219 (1.37%)	1 / 222 (0.45%)	10 / 179 (5.59%)	1 / 71 (1.41%)	15 / 398 (3.77%)
occurrences all number	0	3	1	10	1	18
Vaginal infection
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	2 / 222 (0.90%)	0 / 179 (0.00%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	2	0	0	2
Vaginitis bacterial
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	1 / 222 (0.45%)	2 / 179 (1.12%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	1	1	2	0	0
Viral infection
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	0 / 179 (0.00%)	2 / 71 (2.82%)	3 / 398 (0.75%)
occurrences all number	0	1	0	0	2	3
Viral pharyngitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Viral upper respiratory tract infection
subjects affected / exposed	3 / 220 (1.36%)	2 / 219 (0.91%)	2 / 222 (0.90%)	5 / 179 (2.79%)	1 / 71 (1.41%)	16 / 398 (4.02%)
occurrences all number	3	2	2	6	1	20
Vulvitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Vulvovaginal candidiasis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	2 / 179 (1.12%)	0 / 71 (0.00%)	3 / 398 (0.75%)
occurrences all number	0	0	0	2	0	4
Vulvovaginal mycotic infection
subjects affected / exposed	2 / 220 (0.91%)	0 / 219 (0.00%)	2 / 222 (0.90%)	1 / 179 (0.56%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	2	0	2	2	0	2
Wound infection
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	0	1	0	2
Metabolism and nutrition disorders
Abnormal loss of weight
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Carbohydrate intolerance
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Decreased appetite
subjects affected / exposed	2 / 220 (0.91%)	1 / 219 (0.46%)	1 / 222 (0.45%)	1 / 179 (0.56%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	2	1	1	1	0	1
Dehydration
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	2 / 179 (1.12%)	0 / 71 (0.00%)	3 / 398 (0.75%)
occurrences all number	0	0	0	2	0	3
Diabetes mellitus
subjects affected / exposed	2 / 220 (0.91%)	0 / 219 (0.00%)	0 / 222 (0.00%)	2 / 179 (1.12%)	0 / 71 (0.00%)	8 / 398 (2.01%)
occurrences all number	2	0	0	2	0	8
Glucose tolerance impaired
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Gout
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	2 / 179 (1.12%)	0 / 71 (0.00%)	7 / 398 (1.76%)
occurrences all number	0	0	0	2	0	7
Hypercalcaemia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Hypercholesterolaemia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	1 / 179 (0.56%)	1 / 71 (1.41%)	2 / 398 (0.50%)
occurrences all number	0	0	1	1	1	2
Hyperglycaemia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	6 / 398 (1.51%)
occurrences all number	0	0	0	0	1	7
Hyperkalaemia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Hyperlipidaemia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	2 / 179 (1.12%)	1 / 71 (1.41%)	4 / 398 (1.01%)
occurrences all number	0	0	0	2	1	5
Hyperphosphataemia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Hypertriglyceridaemia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	2 / 222 (0.90%)	2 / 179 (1.12%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	2	2	0	1
Hyperuricaemia
subjects affected / exposed	1 / 220 (0.45%)	2 / 219 (0.91%)	1 / 222 (0.45%)	2 / 179 (1.12%)	1 / 71 (1.41%)	4 / 398 (1.01%)
occurrences all number	1	2	1	3	1	4
Hypoalbuminaemia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Hypocalcaemia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Hypoglycaemia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Hypokalaemia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	1 / 222 (0.45%)	1 / 179 (0.56%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	0	1	1	0	4
Hypomagnesaemia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Hyponatraemia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	2
Hypophosphataemia
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Lactose intolerance
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Metabolic acidosis
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	1 / 179 (0.56%)	0 / 71 (0.00%)	0 / 398 (0.00%)
occurrences all number	0	0	0	1	0	0
Obesity
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Type 1 diabetes mellitus
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	0 / 71 (0.00%)	1 / 398 (0.25%)
occurrences all number	0	0	0	0	0	1
Type 2 diabetes mellitus
subjects affected / exposed	0 / 220 (0.00%)	1 / 219 (0.46%)	0 / 222 (0.00%)	3 / 179 (1.68%)	0 / 71 (0.00%)	2 / 398 (0.50%)
occurrences all number	0	1	0	3	0	2
Vitamin B12 deficiency
subjects affected / exposed	0 / 220 (0.00%)	0 / 219 (0.00%)	0 / 222 (0.00%)	0 / 179 (0.00%)	1 / 71 (1.41%)	0 / 398 (0.00%)
occurrences all number	0	0	0	0	1	0
Vitamin D deficiency
subjects affected / exposed	1 / 220 (0.45%)	0 / 219 (0.00%)	0 / 222 (0.00%)	2 / 179 (1.12%)	1 / 71 (1.41%)	2 / 398 (0.50%)
occurrences all number	1	0	0	2	1	2

More information

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Were there any global substantial amendments to the protocol? Yes

17 Jul 2012

Safety reporting language was updated to be compliant with a requirement in the current version of the European Union Clinical Trial Directive. Language regarding topical therapy was clarified to specify that topical therapy containing urea was not permitted through week 52.

17 Oct 2013

Clarified safety follow-up and hepatotoxicity criteria. Added guidance regarding additional safety follow-up visit/end of study visit and corresponding changes to study duration.

26 Mar 2014

Added the Columbia-Suicide Severity Rating Scale, and Patient Health Questionnaire-8 depression scale assessments. Changed the timing of the planned interim analyses from after approximately 80% of subjects had reached week 132 to performed as deemed necessary.

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 Phase 3 Study to Evaluate the Efficacy, Safety, and Effect of Withdrawal and Retreatment With Brodalumab in Subjects With Moderate to Severe Plaque Psoriasis: AMAGINE-1

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Participants with a 75% or Greater Improvement from Baseline in Psoriasis Area and Severity Index (PASI 75) at Week 12

Primary: Percentage of Participants with a 75% or Greater Improvement from Baseline in Psoriasis Area and Severity Index (PASI 75) at Week 12

Primary: Percentage of Participants with a Static Physician’s Global Assessment (sPGA) of Clear or Almost Clear at Week 12

Primary: Percentage of Participants with a Static Physician’s Global Assessment (sPGA) of Clear or Almost Clear at Week 12

Secondary: Percentage of Participants with a 100% Improvement from Baseline in PASI (PASI 100) at Week 12

Secondary: Percentage of Participants with a 100% Improvement from Baseline in PASI (PASI 100) at Week 12

Secondary: Percentage of Participants with an sPGA of Clear at Week 12

Secondary: Percentage of Participants with an sPGA of Clear at Week 12

Secondary: Percentage of Rerandomized Participants with an sPGA of Clear or Almost Clear at Week 52

Secondary: Percentage of Rerandomized Participants with an sPGA of Clear or Almost Clear at Week 52

Secondary: Percentage of Participants with a Psoriasis Symptom Inventory (PSI) Response at Week 12

Secondary: Percentage of Participants with a Psoriasis Symptom Inventory (PSI) Response at Week 12

Secondary: Time to sPGA Response During the Induction Phase

Secondary: Time to sPGA Response During the Induction Phase

Secondary: Time to PASI Response During the Induction Phase

Secondary: Time to PASI Response During the Induction Phase

Secondary: Percentage of Participants with an sPGA of Clear or Almost Clear at Each Visit in the Induction Phase

Secondary: Percentage of Participants with an sPGA of Clear or Almost Clear at Each Visit in the Induction Phase

Secondary: Percentage of Participants with an sPGA of Clear at Each Visit in the Induction Phase

Secondary: Percentage of Participants with an sPGA of Clear at Each Visit in the Induction Phase

Secondary: Percentage of Participants with a PASI 75 at Each Visit in the Induction Phase

Secondary: Percentage of Participants with a PASI 75 at Each Visit in the Induction Phase

Secondary: Percentage of Participants with a PASI 100 at Each Visit in the Induction Phase

Secondary: Percentage of Participants with a PASI 100 at Each Visit in the Induction Phase

Secondary: Percentage of Participants with a PASI 50 at Each Visit in the Induction Phase

Secondary: Percentage of Participants with a PASI 50 at Each Visit in the Induction Phase

Secondary: Percentage of Participants with a PASI 90 at Each Visit in the Induction Phase

Secondary: Percentage of Participants with a PASI 90 at Each Visit in the Induction Phase

Secondary: Percent Improvement From Baseline in PASI During the Induction Phase

Secondary: Percent Improvement From Baseline in PASI During the Induction Phase

Secondary: Absolute PASI Score During the Induction Phase

Secondary: Absolute PASI Score During the Induction Phase

Secondary: Body Surface Area Involvement During the Induction Phase

Secondary: Body Surface Area Involvement During the Induction Phase

Secondary: Improvement From Baseline in NAPSI Score at Week 12

Secondary: Improvement From Baseline in NAPSI Score at Week 12

Secondary: Percent Improvement From Baseline in Psoriasis Scalp Severity Index Score

Secondary: Percent Improvement From Baseline in Psoriasis Scalp Severity Index Score

Secondary: Improvement From Study Baseline in Scalp Surface Area (SSA) During the Induction Phase

Secondary: Improvement From Study Baseline in Scalp Surface Area (SSA) During the Induction Phase

Secondary: Percentage of Participants with an sPGA of Clear at Week 52

Secondary: Percentage of Participants with an sPGA of Clear at Week 52

Secondary: Percentage of Participants with a PASI 75 at Week 52

Secondary: Percentage of Participants with a PASI 75 at Week 52

Secondary: Percentage of Participants with a PASI 90 at Week 52

Secondary: Percentage of Participants with a PASI 90 at Week 52

Secondary: Percentage of Participants with a PASI 100 at Week 52

Secondary: Percentage of Participants with a PASI 100 at Week 52

Secondary: Percent Improvement From Baseline in PASI Score During the Withdrawal Phase

Secondary: Percent Improvement From Baseline in PASI Score During the Withdrawal Phase

Secondary: Time to sPGA Response During the Retreatment Phase

Secondary: Time to sPGA Response During the Retreatment Phase

Secondary: Time to PASI 75 Response During the Retreatment Phase

Secondary: Time to PASI 75 Response During the Retreatment Phase

Secondary: Time to PASI 90 Response During the Retreatment Phase

Secondary: Time to PASI 90 Response During the Retreatment Phase

Secondary: Time to PASI 100 Response During the Retreatment Phase

Secondary: Time to PASI 100 Response During the Retreatment Phase

Secondary: Percentage of Participants with an sPGA Response During the Retreatment Phase

Secondary: Percentage of Participants with an sPGA Response During the Retreatment Phase

Secondary: Percentage of Participants with a PASI 75 Response During the Retreatment Phase

Secondary: Percentage of Participants with a PASI 75 Response During the Retreatment Phase

Secondary: Percentage of Participants with a PASI 90 Response During the Retreatment Phase

Secondary: Percentage of Participants with a PASI 90 Response During the Retreatment Phase

Secondary: Percentage of Participants with a PASI 100 Response During the Retreatment Phase

Secondary: Percentage of Participants with a PASI 100 Response During the Retreatment Phase

Secondary: Percentage of Participants with a Dermatology Life Quality Index (DLQI) Response at Week 12

Secondary: Percentage of Participants with a Dermatology Life Quality Index (DLQI) Response at Week 12

Secondary: Treatment Satisfaction at Week 12

Secondary: Treatment Satisfaction at Week 12

Clinical Trial Results:
A Phase 3 Study to Evaluate the Efficacy, Safety, and Effect of Withdrawal and Retreatment With Brodalumab in Subjects With Moderate to Severe Plaque Psoriasis: AMAGINE-1