Download PDF

Clinical Trial Results:
A phase III, randomized, double-blind, placebo-controlled multicenter study of subcutaneous secukinumab in autoinjectors, to demonstrate efficacy at 24 weeks and to assess the long term safety, tolerability and efficacy up to 3 years in subjects with active Psoriatic Arthritis

Summary
EudraCT number	2013-004002-25
Trial protocol	GB IT ES NL CZ BG
Global end of trial date	28 Mar 2018

Results information
Results version number	v1(current)
This version publication date	14 Mar 2019
First version publication date	14 Mar 2019
Other versions

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

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

CAIN457F2318

ISRCTN number

US NCT number

NCT01989468

WHO universal trial number (UTN)

Sponsor organisation name

Novartis Pharma AG

Sponsor organisation address

CH-4002, Basel, Switzerland,

Public contact

Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@novartis.com

Scientific contact

Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@novartis.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

28 Mar 2018

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

28 Mar 2018

Was the trial ended prematurely?

Main objective of the trial

The primary objective of the study was to demonstrate that the efficacy of secukinumab 150 mg sc or 300 mg sc, at Week 24 was superior to placebo based on proportion of patients achieving American College of Rheumatology 20 (ACR20) response in patients with active PsA.

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.

Background therapy

Evidence for comparator

Actual start date of recruitment

10 Apr 2014

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 33

Country: Number of subjects enrolled

Bulgaria: 16

Country: Number of subjects enrolled

Canada: 8

Country: Number of subjects enrolled

Czech Republic: 52

Country: Number of subjects enrolled

Germany: 68

Country: Number of subjects enrolled

United Kingdom: 51

Country: Number of subjects enrolled

Italy: 32

Country: Number of subjects enrolled

Netherlands: 18

Country: Number of subjects enrolled

Russian Federation: 61

Country: Number of subjects enrolled

Spain: 22

Country: Number of subjects enrolled

Switzerland: 5

Country: Number of subjects enrolled

United States: 48

Worldwide total number of subjects

414

EEA total number of subjects

259

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)

367

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Patients were randomized to 1 of 3 treatment arms (1:1:1) and planned to be treated for 156 weeks. Placebo non-responders had the option to be re-randomized at Week 16 and placebo responders had the option to be re-randomized at Week 24. Thus, of the 137 original placebo patients 64 were re-randomized to AIN457 150 mg and 65 to AIN457 300 mg.

Screening details

A screening period (SCR) running up to 10 weeks before randomization was used to assess eligibility.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

AIN457 150 mg

Arm description

1 s.c. Secukinumab 150 mg autoinjector at Baseline, Weeks 1, 2, 3, 4, followed by dosing every four weeks starting at Week 4.

Arm type

Experimental

Investigational medicinal product name

Secukinumab

Investigational medicinal product code

Other name

Secukinumab 150 mg

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

1 s.c. Secukinumab 150 mg autoinjector at Baseline, Weeks 1, 2, 3, 4, followed by dosing every four weeks starting at Week 4

AIN457 300 mg

Arm description

2 s.c. Secukinumab 150 mg autoinjector at Baseline, Weeks 1, 2, 3, 4, followed by dosing every four weeks starting at Week 4.

Arm type

Experimental

Investigational medicinal product name

Secukinumab

Investigational medicinal product code

Other name

Secukinumab 300 mg

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

2 s.c. Secukinumab 150 mg autoinjector at Baseline, Weeks 1, 2, 3, 4, followed by dosing every four weeks starting at Week 4

Placebo_AIN457 150 mg

Arm description

Placebo switch to Secukinumab/AIN457 150 mg

Arm type

Placebo

Investigational medicinal product name

Secukinumab

Investigational medicinal product code

Other name

Secukinumab 150 mg

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

1 s.c. Secukinumab 150 mg autoinjector at Baseline, Weeks 1, 2, 3, 4, followed by dosing every four weeks starting at Week 4

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

Matching Placebo at Baseline, Weeks 1, 2, 3, 4, followed by dosing every four weeks starting at Week 4

Placebo_AIN457 300 mg

Arm description

Placebo switch to Secukinumab/AIN457 300 mg

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

Matching Placebo at Baseline, Weeks 1, 2, 3, 4, followed by dosing every four weeks starting at Week 4

Investigational medicinal product name

Secukinumab

Investigational medicinal product code

Other name

Secukinumab 300 mg

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

2 s.c. Secukinumab 150 mg autoinjector at Baseline, Weeks 1, 2, 3, 4, followed by dosing every four weeks starting at Week 4

Placebo not rerandomized

Arm description

Matching Placebo at Beseline, Weeks 1, 2, 3, 4, followed by dosing every four weeks starting at Week 4.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

Matching Placebo at Baseline, Weeks 1, 2, 3, 4, followed by dosing every four weeks starting at Week 4

Number of subjects in period 1	AIN457 150 mg	AIN457 300 mg	Placebo_AIN457 150 mg	Placebo_AIN457 300 mg	Placebo not rerandomized
Started	138	139	64	65	8
Completed	91	102	45	49	0
Not completed	47	37	19	16	8
Adverse event, serious fatal	3	-	1	-	-
Physician decision	4	1	-	1	-
Adverse event, non-fatal	10	15	4	5	4
Technical Problems	3	1	3	1	-
Pregnancy	-	1	-	-	-
Subject Guardian Decision	11	6	4	4	1
Lost to follow-up	5	2	-	1	1
Lack of efficacy	11	11	7	4	2

Baseline characteristics

Top of page

Reporting group title

Overall Study

Reporting group description

Reporting group values	Overall Study	Total
Number of subjects	414	414
Age Categorical
Units: Subjects
<=18 years	0	0
Between 18 and 65 years	367	367
>=65 years	47	47
Sex: Female, Male
Units: Subjects
Female	227	227
Male	187	187
Race/Ethnicity, Customized
Units: Subjects
American Indian or Alaska Native	2	2
Asian	9	9
White	392	392
Other	11	11

Subject analysis set title

Placebo

Subject analysis set type

Full analysis

Subject analysis set description

Matching Placebo at Beseline, Weeks 1, 2, 3, 4, followed by dosing every four weeks starting at Week 4.

Subject analysis set title

Placebo

Subject analysis set type

Full analysis

Subject analysis set description

Matching Placebo at Beseline, Weeks 1, 2, 3, 4, followed by dosing every four weeks starting at Week 4.

Subject analysis set title

Placebo

Subject analysis set type

Full analysis

Subject analysis set description

Matching Placebo at Beseline, Weeks 1, 2, 3, 4, followed by dosing every four weeks starting at Week 4.

Subject analysis set title

Placebo

Subject analysis set type

Full analysis

Subject analysis set description

Matching Placebo at Beseline, Weeks 1, 2, 3, 4, followed by dosing every four weeks starting at Week 4.

Subject analysis set title

Any AIN457 150 mg

Subject analysis set type

Full analysis

Subject analysis set description

Any patients exposed to AIN457 150 mg

Subject analysis set title

Any AIN457 300 mg

Subject analysis set type

Full analysis

Subject analysis set description

Any patients exposed to AIN457 300 mg

Subject analysis set title

Any AIN457

Subject analysis set type

Full analysis

Subject analysis set description

Any patients exposed to AIN457

Subject analysis sets values	Placebo	Placebo	Placebo	Placebo	Any AIN457 150 mg	Any AIN457 300 mg	Any AIN457
Number of subjects	137	59	36	98	202	284	406
Age Categorical
Units: Subjects
<=18 years	0
Between 18 and 65 years	118
>=65 years	19
Age continuous
Units:
	( )	( )	( )	( )	( )	( )	( )
Sex: Female, Male
Units: Subjects
Female	78
Male	59
Race/Ethnicity, Customized
Units: Subjects
American Indian or Alaska Native	0
Asian	4
White	133
Other	0

End points

Top of page

Reporting group title

AIN457 150 mg

Reporting group description

1 s.c. Secukinumab 150 mg autoinjector at Baseline, Weeks 1, 2, 3, 4, followed by dosing every four weeks starting at Week 4.

Reporting group title

AIN457 300 mg

Reporting group description

2 s.c. Secukinumab 150 mg autoinjector at Baseline, Weeks 1, 2, 3, 4, followed by dosing every four weeks starting at Week 4.

Reporting group title

Placebo_AIN457 150 mg

Reporting group description

Placebo switch to Secukinumab/AIN457 150 mg

Reporting group title

Placebo_AIN457 300 mg

Reporting group description

Placebo switch to Secukinumab/AIN457 300 mg

Reporting group title

Placebo not rerandomized

Reporting group description

Matching Placebo at Beseline, Weeks 1, 2, 3, 4, followed by dosing every four weeks starting at Week 4.

Subject analysis set title

Placebo

Subject analysis set type

Full analysis

Subject analysis set description

Matching Placebo at Beseline, Weeks 1, 2, 3, 4, followed by dosing every four weeks starting at Week 4.

Subject analysis set title

Placebo

Subject analysis set type

Full analysis

Subject analysis set description

Matching Placebo at Beseline, Weeks 1, 2, 3, 4, followed by dosing every four weeks starting at Week 4.

Subject analysis set title

Placebo

Subject analysis set type

Full analysis

Subject analysis set description

Matching Placebo at Beseline, Weeks 1, 2, 3, 4, followed by dosing every four weeks starting at Week 4.

Subject analysis set title

Placebo

Subject analysis set type

Full analysis

Subject analysis set description

Matching Placebo at Beseline, Weeks 1, 2, 3, 4, followed by dosing every four weeks starting at Week 4.

Subject analysis set title

Any AIN457 150 mg

Subject analysis set type

Full analysis

Subject analysis set description

Any patients exposed to AIN457 150 mg

Subject analysis set title

Any AIN457 300 mg

Subject analysis set type

Full analysis

Subject analysis set description

Any patients exposed to AIN457 300 mg

Subject analysis set title

Any AIN457

Subject analysis set type

Full analysis

Subject analysis set description

Any patients exposed to AIN457

Primary: Proportion of patients achieving American College of Rheumatology 20 (ACR20) response criteria on secukinumab versus placebo at Week 24

Top of page

End point title

Proportion of patients achieving American College of Rheumatology 20 (ACR20) response criteria on secukinumab versus placebo at Week 24 ^[1] ^[2]

End point description

A patient will be considered as improved according the ACR20 criteria if she/he has at least 20% decrease in the swollen and tender joint count, and at least 20% improvements in 3 of the following 5 criteria: physical disability on the Health Assessment Questionnaire; pain score on a visual analog scale; patient global assessment; physician global assessment; and acute phase reactant [either erythrocyte sedimentation rate (ESR) or high sensitivity C-reactive protein (hsCRP)]

End point type

Primary

End point timeframe

Week 24

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: AIN457 Baseline Period Arms (AIN457 150mg, AIN457 300mg) included under Arm Reporting Groups "Overall Study" and Placebo included under "Subject Analysis Set" => Summary descriptive analysis done.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: AIN457 Baseline Period Arms (AIN457 150mg, AIN457 300mg) included under Arm Reporting Groups "Overall Study" and Placebo included under "Subject Analysis Set" => Summary descriptive analysis done.

End point values	AIN457 150 mg	AIN457 300 mg	Placebo
Number of subjects analysed	138	139	137
Units: Participants	58	67	22

No statistical analyses for this end point

Secondary: Proportion of patients achieving American College of Rheumatology 50 (ACR50) response criteria on secukinumab versus placebo at Week 24

Top of page

End point title

Proportion of patients achieving American College of Rheumatology 50 (ACR50) response criteria on secukinumab versus placebo at Week 24 ^[3]

End point description

A patient will be considered as improved according the ACR50 criteria if she/he has at least 50% decreases in the swollen and tender joint count, and at least 50% improvements in 3 of the following 5 criteria: physical disability on the Health Assessment Questionnaire; pain score on a visual analog scale; patient global assessment; physician global assessment; and acute phase reactant [either erythrocyte sedimentation rate (ESR) or high sensitivity C-reactive protein (hsCRP)]

End point type

Secondary

End point timeframe

Week 24

Notes
[3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: AIN457 Baseline Period Arms (AIN457 150mg, AIN457 300mg) included under Arm Reporting Groups "Overall Study" and Placebo included under "Subject Analysis Set" => Summary descriptive analysis done.

End point values	AIN457 150 mg	AIN457 300 mg	Placebo
Number of subjects analysed	138	139	137
Units: Participants	26	48	12

No statistical analyses for this end point

Secondary: Change from baseline in Disease Activity Score for 28 joints (DAS28-CRP) (utilizing hsCRP) in subjects treated with secukinumab versus placebo at Week 24

Top of page

End point title

Change from baseline in Disease Activity Score for 28 joints (DAS28-CRP) (utilizing hsCRP) in subjects treated with secukinumab versus placebo at Week 24 ^[4]

End point description

DAS28-CRP is a measure of disease activity based on 28-Swollen and Tender Joint Count [proximal interphalangeal joints (10 joints) metacarpophalangeal joints (10) wrists (2) elbows (2) shoulders (2) knees (2)], CRP, and the Patient’s Global Assessment of disease activity. Values range from 2.0 to 10.0 where higher values mean a higher disease activity. DAS28-CRP < 2.6 is interpreted as remission.

End point type

Secondary

End point timeframe

Week 24

Notes
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: AIN457 Baseline Period Arms (AIN457 150mg, AIN457 300mg) included under Arm Reporting Groups "Overall Study" and Placebo included under "Subject Analysis Set" => Summary descriptive analysis done.

End point values	AIN457 150 mg	AIN457 300 mg	Placebo
Number of subjects analysed	138	139	137
Units: Unit on a scale
least squares mean (standard error)	-1.24 ( 0.095 )	-1.56 ( 0.093 )	-0.64 ( 0.127 )

No statistical analyses for this end point

Secondary: Proportion of subjects achieving a Psoriatic Area and Severity Index 75 (PASI75) response in subjects on secukinumab versus placebo at Week 24

Top of page

End point title

Proportion of subjects achieving a Psoriatic Area and Severity Index 75 (PASI75) response in subjects on secukinumab versus placebo at Week 24 ^[5]

End point description

PASI takes into account the extent of the disease, as well as the severity of erythema, scaling, and thickness in different body areas affected by psoriasis. A PASI75 represents an improvement in the PASI score of at least 75% as compared with baseline.

End point type

Secondary

End point timeframe

Week 24

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: AIN457 Baseline Period Arms (AIN457 150mg, AIN457 300mg) included under Arm Reporting Groups "Overall Study" and Placebo included under "Subject Analysis Set" => Summary descriptive analysis done.

End point values	AIN457 150 mg	AIN457 300 mg	Placebo
Number of subjects analysed	68	62	59
Units: Participants	34	29	6

No statistical analyses for this end point

Secondary: Change from baseline in Physical function component of the short-form health survey (SF-36-PCS) in subjects treated with secukinumab versus placebo at Week 24

Top of page

End point title

Change from baseline in Physical function component of the short-form health survey (SF-36-PCS) in subjects treated with secukinumab versus placebo at Week 24 ^[6]

End point description

SF-36 is a 36 item questionnaire which measures Quality of Life across eight domains, which are both physically and emotionally based. Two overall summary scores, the Physical Component Summary (PCS) and Mental Component Summary (MCS) can be computed.

End point type

Secondary

End point timeframe

Week 24

Notes
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: AIN457 Baseline Period Arms (AIN457 150mg, AIN457 300mg) included under Arm Reporting Groups "Overall Study" and Placebo included under "Subject Analysis Set" => Summary descriptive analysis done.

End point values	AIN457 150 mg	AIN457 300 mg	Placebo
Number of subjects analysed	138	139	137
Units: Unit on a scale
least squares mean (standard error)
Mental Component Summary (MCS)	1.68 ( 0.837 )	4.41 ( 0.822 )	-0.10 ( 1.142 )
Physical Component Summary (PCS)	3.42 ( 0.600 )	6.46 ( 0.590 )	2.94 ( 0.830 )

No statistical analyses for this end point

Secondary: Psoriatic Area and Severity Index 90 (PASI90) response in subjects treated with secukinumab versus placebo at Week 24

Top of page

End point title

Psoriatic Area and Severity Index 90 (PASI90) response in subjects treated with secukinumab versus placebo at Week 24 ^[7]

End point description

PASI takes into account the extent of the disease, as well as the severity of erythema, scaling, and thickness in different body areas affected by psoriasis. A PASI90 represents an improvement in the PASI score of at least 90% as compared with baseline.

End point type

Secondary

End point timeframe

Week 24

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: AIN457 Baseline Period Arms (AIN457 150mg, AIN457 300mg) included under Arm Reporting Groups "Overall Study" and Placebo included under "Subject Analysis Set" => Summary descriptive analysis done.

End point values	AIN457 150 mg	AIN457 300 mg	Placebo
Number of subjects analysed	68	62	59
Units: Participants	25	21	4

No statistical analyses for this end point

Secondary: Change from baseline in Health Assessment Questionnaire – Disability Index (HAQ-DI score) in subjects treated with secukinumab versus placebo at Week 24

Top of page

End point title

Change from baseline in Health Assessment Questionnaire – Disability Index (HAQ-DI score) in subjects treated with secukinumab versus placebo at Week 24 ^[8]

End point description

The disability assessment component of the HAQ assesses a subjects level of functional ability and includes questions of fine movements of the upper extremity, locomotor activities of the lower extremity, and activities that involve both upper and lower extremitites.

End point type

Secondary

End point timeframe

Week 24

Notes
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: AIN457 Baseline Period Arms (AIN457 150mg, AIN457 300mg) included under Arm Reporting Groups "Overall Study" and Placebo included under "Subject Analysis Set" => Summary descriptive analysis done.

End point values	AIN457 150 mg	AIN457 300 mg	Placebo
Number of subjects analysed	138	139	137
Units: Unit on a scale
least squares mean (standard error)	-0.27 ( 0.043 )	-0.38 ( 0.042 )	-0.17 ( 0.055 )

No statistical analyses for this end point

Secondary: Overall safety and tolerability

Top of page

End point title

Overall safety and tolerability ^[9]

End point description

Analysis of frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by primary System Organ Class (SOC).

End point type

Secondary

End point timeframe

From first dose of study treatment to last study visit, up to 3 years

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: AIN457 Baseline Period Arms (AIN457 150mg, AIN457 300mg) included under Arm Reporting Groups "Overall Study" and Placebo included under "Subject Analysis Set" => Summary descriptive analysis done.

End point values	AIN457 150 mg	AIN457 300 mg	Placebo	Any AIN457 150 mg	Any AIN457 300 mg	Any AIN457
Number of subjects analysed	138	139	137	202	284	406
Units: Participants
number (not applicable)
AEs by Primary System Organ Class (SOC)	176	230	81	176	230	363
SAEs by Primary System Organ Class (SOC)	42	4	9	42	35	76
Deaths by Primary System Organ Class (SOC)	4	0	0	4	0	4

No statistical analyses for this end point

Secondary: Proportion of patients with Dactylitis at Week 24 in the subset of patients who had dactylitis at Baseline

Top of page

End point title

Proportion of patients with Dactylitis at Week 24 in the subset of patients who had dactylitis at Baseline ^[10]

End point description

The presence of dactylitis was assessed by dactylitis count (number of fingers and toes with dactylitis, with a range of 0-20). If dactylitis is present with any finger or toe, the patient is counted as a patient with dactylitis.

End point type

Secondary

End point timeframe

Week 24

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: AIN457 Baseline Period Arms (AIN457 150mg, AIN457 300mg) included under Arm Reporting Groups "Overall Study" and Placebo included under "Subject Analysis Set" => Summary descriptive analysis done.

End point values	AIN457 150 mg	AIN457 300 mg	Placebo
Number of subjects analysed	36	46	36
Units: Participants	22	24	31

No statistical analyses for this end point

Secondary: Proportion of patients with Enthesitis at Week 24 in the subset of patients who had enthesitis at Baseline

Top of page

End point title

Proportion of patients with Enthesitis at Week 24 in the subset of patients who had enthesitis at Baseline ^[11]

End point description

The presence of Enthesitis was assessed using a validated enthesitis index that uses 6 sites for evaluation of enthesitis: lateral epicondyle humerus L + R, proximal achilles L + R and medial condyle femur. If enthesitis is present at any of the 6 sites, the subject is counted as a subject with enthesitis.

End point type

Secondary

End point timeframe

Week 24

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: AIN457 Baseline Period Arms (AIN457 150mg, AIN457 300mg) included under Arm Reporting Groups "Overall Study" and Placebo included under "Subject Analysis Set" => Summary descriptive analysis done.

End point values	AIN457 150 mg	AIN457 300 mg	Placebo
Number of subjects analysed	95	88	98
Units: Participants	60	53	83

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

All Adverse Events (AEs) are reported in this record from date of First Patient First Treatment (FPFT) until end of treatment exposure + 84 days safety follow-up.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

21.0

Reporting group title

Any AIN457 150 mg

Reporting group description

Any AIN457 150 mg

Reporting group title

Any AIN457 300 mg

Reporting group description

Any AIN457 300 mg

Reporting group title

Any AIN457

Reporting group description

Any AIN457

Reporting group title

Placebo

Reporting group description

Placebo

Serious adverse events	Any AIN457 150 mg	Any AIN457 300 mg	Any AIN457	Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	42 / 202 (20.79%)	35 / 284 (12.32%)	76 / 406 (18.72%)	9 / 137 (6.57%)
number of deaths (all causes)	4	0	4	0
number of deaths resulting from adverse events	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cancer pain
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Chronic lymphocytic leukaemia
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Colon adenoma
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Follicular thyroid cancer
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Invasive papillary breast carcinoma
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lip squamous cell carcinoma
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Melanocytic naevus
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metastases to central nervous system
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
Metastases to liver
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
Metastases to spine
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
Ovarian cancer stage IV
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatic carcinoma
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
Papillary thyroid cancer
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Phyllodes tumour
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Salivary gland neoplasm
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Small cell lung cancer metastatic
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
Vascular disorders
Circulatory collapse
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypertension
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	1 / 137 (0.73%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Peripheral artery thrombosis
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Varicose vein
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Non-cardiac chest pain
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Cystocele
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Menorrhagia
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ovarian cyst
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ovarian cyst torsion
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rectocele
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Uterovaginal prolapse
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cough
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nasal turbinate hypertrophy
subjects affected / exposed	0 / 202 (0.00%)	0 / 284 (0.00%)	0 / 406 (0.00%)	1 / 137 (0.73%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary mass
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Depression
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sopor
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Suicidal ideation
subjects affected / exposed	1 / 202 (0.50%)	1 / 284 (0.35%)	2 / 406 (0.49%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Product issues
Device dislocation
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	1 / 137 (0.73%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Device loosening
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Weight decreased
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Ankle fracture
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac valve rupture
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cervical vertebral fracture
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Femur fracture
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Humerus fracture
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Joint dislocation
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ligament rupture
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lumbar vertebral fracture
subjects affected / exposed	0 / 202 (0.00%)	2 / 284 (0.70%)	2 / 406 (0.49%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Radius fracture
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Road traffic accident
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sternal fracture
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tendon rupture
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Traumatic arthrosis
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Traumatic fracture
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Angina pectoris
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Angina unstable
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Aortic valve incompetence
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Arrhythmia
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Arteriosclerosis coronary artery
subjects affected / exposed	0 / 202 (0.00%)	0 / 284 (0.00%)	0 / 406 (0.00%)	1 / 137 (0.73%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	1 / 202 (0.50%)	1 / 284 (0.35%)	2 / 406 (0.49%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Atrial flutter
subjects affected / exposed	0 / 202 (0.00%)	0 / 284 (0.00%)	0 / 406 (0.00%)	1 / 137 (0.73%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Atrioventricular block complete
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	1 / 137 (0.73%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Atrioventricular block first degree
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac failure
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
Cardiac failure chronic
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiogenic shock
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diastolic dysfunction
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Left ventricular hypertrophy
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Mitral valve incompetence
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	2 / 202 (0.99%)	0 / 284 (0.00%)	2 / 406 (0.49%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Aphasia
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cerebral ischaemia
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Coma
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Depressed level of consciousness
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Facial paresis
subjects affected / exposed	0 / 202 (0.00%)	0 / 284 (0.00%)	0 / 406 (0.00%)	1 / 137 (0.73%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Headache
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hemiplegia
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ischaemic stroke
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lacunar infarction
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Quadriparesis
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Lymphadenitis
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lymphadenopathy
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ear and labyrinth disorders
Sudden hearing loss
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vestibular disorder
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Cataract
subjects affected / exposed	1 / 202 (0.50%)	1 / 284 (0.35%)	2 / 406 (0.49%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Retinal detachment
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Anal prolapse
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Colitis ulcerative
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	1 / 137 (0.73%)
occurrences causally related to treatment / all	0 / 0	1 / 1	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Duodenal ulcer
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastritis
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Inflammatory bowel disease
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lower gastrointestinal haemorrhage
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Biliary dyskinesia
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cholecystitis
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cholecystitis chronic
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cholelithiasis
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Dermal cyst
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Eczema
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Urethral stenosis
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	2 / 202 (0.99%)	0 / 284 (0.00%)	2 / 406 (0.49%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Arthritis
subjects affected / exposed	1 / 202 (0.50%)	1 / 284 (0.35%)	2 / 406 (0.49%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Fibromyalgia
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Foot deformity
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Intervertebral disc protrusion
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal chest pain
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	2 / 202 (0.99%)	4 / 284 (1.41%)	6 / 406 (1.48%)	1 / 137 (0.73%)
occurrences causally related to treatment / all	0 / 2	0 / 5	0 / 7	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psoriatic arthropathy
subjects affected / exposed	0 / 202 (0.00%)	0 / 284 (0.00%)	0 / 406 (0.00%)	1 / 137 (0.73%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Abscess jaw
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Abscess of salivary gland
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Arthritis bacterial
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	1 / 202 (0.50%)	1 / 284 (0.35%)	2 / 406 (0.49%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	1 / 1	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Campylobacter gastroenteritis
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Device related infection
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	0 / 202 (0.00%)	2 / 284 (0.70%)	2 / 406 (0.49%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 2	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Eczema infected
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Enterococcal sepsis
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Erysipelas
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infectious mononucleosis
subjects affected / exposed	0 / 202 (0.00%)	0 / 284 (0.00%)	0 / 406 (0.00%)	1 / 137 (0.73%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Joint abscess
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Periodontitis
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	3 / 202 (1.49%)	1 / 284 (0.35%)	4 / 406 (0.99%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	1 / 3	2 / 3	3 / 6	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
Staphylococcal infection
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tonsillitis
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	2 / 202 (0.99%)	0 / 284 (0.00%)	2 / 406 (0.49%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Wound infection
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Hypoglycaemia
subjects affected / exposed	1 / 202 (0.50%)	0 / 284 (0.00%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypokalaemia
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Obesity
subjects affected / exposed	0 / 202 (0.00%)	1 / 284 (0.35%)	1 / 406 (0.25%)	0 / 137 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 2%

Non-serious adverse events	Any AIN457 150 mg	Any AIN457 300 mg	Any AIN457	Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	153 / 202 (75.74%)	201 / 284 (70.77%)	320 / 406 (78.82%)	65 / 137 (47.45%)
Vascular disorders
Hypertension
subjects affected / exposed	11 / 202 (5.45%)	15 / 284 (5.28%)	26 / 406 (6.40%)	2 / 137 (1.46%)
occurrences all number	11	18	29	2
General disorders and administration site conditions
Fatigue
subjects affected / exposed	16 / 202 (7.92%)	10 / 284 (3.52%)	26 / 406 (6.40%)	2 / 137 (1.46%)
occurrences all number	17	17	34	2
Injection site erythema
subjects affected / exposed	1 / 202 (0.50%)	2 / 284 (0.70%)	3 / 406 (0.74%)	3 / 137 (2.19%)
occurrences all number	1	2	3	5
Non-cardiac chest pain
subjects affected / exposed	5 / 202 (2.48%)	2 / 284 (0.70%)	7 / 406 (1.72%)	1 / 137 (0.73%)
occurrences all number	5	2	7	1
Oedema peripheral
subjects affected / exposed	1 / 202 (0.50%)	6 / 284 (2.11%)	7 / 406 (1.72%)	0 / 137 (0.00%)
occurrences all number	1	6	7	0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	5 / 202 (2.48%)	2 / 284 (0.70%)	7 / 406 (1.72%)	0 / 137 (0.00%)
occurrences all number	5	2	7	0
Cough
subjects affected / exposed	17 / 202 (8.42%)	12 / 284 (4.23%)	29 / 406 (7.14%)	6 / 137 (4.38%)
occurrences all number	22	15	37	6
Oropharyngeal pain
subjects affected / exposed	10 / 202 (4.95%)	15 / 284 (5.28%)	25 / 406 (6.16%)	1 / 137 (0.73%)
occurrences all number	10	18	28	1
Psychiatric disorders
Depression
subjects affected / exposed	5 / 202 (2.48%)	3 / 284 (1.06%)	8 / 406 (1.97%)	0 / 137 (0.00%)
occurrences all number	5	3	8	0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	11 / 202 (5.45%)	6 / 284 (2.11%)	17 / 406 (4.19%)	1 / 137 (0.73%)
occurrences all number	12	7	19	1
Aspartate aminotransferase increased
subjects affected / exposed	8 / 202 (3.96%)	3 / 284 (1.06%)	11 / 406 (2.71%)	1 / 137 (0.73%)
occurrences all number	8	3	11	1
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	5 / 202 (2.48%)	11 / 284 (3.87%)	15 / 406 (3.69%)	1 / 137 (0.73%)
occurrences all number	5	12	17	1
Limb injury
subjects affected / exposed	8 / 202 (3.96%)	2 / 284 (0.70%)	10 / 406 (2.46%)	1 / 137 (0.73%)
occurrences all number	9	2	11	1
Cardiac disorders
Palpitations
subjects affected / exposed	5 / 202 (2.48%)	4 / 284 (1.41%)	9 / 406 (2.22%)	0 / 137 (0.00%)
occurrences all number	5	4	9	0
Nervous system disorders
Dizziness
subjects affected / exposed	7 / 202 (3.47%)	3 / 284 (1.06%)	10 / 406 (2.46%)	2 / 137 (1.46%)
occurrences all number	9	3	12	2
Headache
subjects affected / exposed	18 / 202 (8.91%)	18 / 284 (6.34%)	36 / 406 (8.87%)	7 / 137 (5.11%)
occurrences all number	21	25	46	8
Sciatica
subjects affected / exposed	4 / 202 (1.98%)	5 / 284 (1.76%)	9 / 406 (2.22%)	0 / 137 (0.00%)
occurrences all number	4	5	9	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	6 / 202 (2.97%)	3 / 284 (1.06%)	9 / 406 (2.22%)	0 / 137 (0.00%)
occurrences all number	6	3	9	0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	4 / 202 (1.98%)	8 / 284 (2.82%)	12 / 406 (2.96%)	0 / 137 (0.00%)
occurrences all number	4	8	12	0
Abdominal pain upper
subjects affected / exposed	10 / 202 (4.95%)	9 / 284 (3.17%)	17 / 406 (4.19%)	2 / 137 (1.46%)
occurrences all number	12	12	24	2
Constipation
subjects affected / exposed	5 / 202 (2.48%)	6 / 284 (2.11%)	11 / 406 (2.71%)	1 / 137 (0.73%)
occurrences all number	5	6	11	1
Diarrhoea
subjects affected / exposed	20 / 202 (9.90%)	19 / 284 (6.69%)	39 / 406 (9.61%)	2 / 137 (1.46%)
occurrences all number	22	24	46	3
Gastrooesophageal reflux disease
subjects affected / exposed	6 / 202 (2.97%)	6 / 284 (2.11%)	12 / 406 (2.96%)	1 / 137 (0.73%)
occurrences all number	6	6	12	1
Mouth ulceration
subjects affected / exposed	6 / 202 (2.97%)	2 / 284 (0.70%)	8 / 406 (1.97%)	0 / 137 (0.00%)
occurrences all number	7	2	9	0
Nausea
subjects affected / exposed	12 / 202 (5.94%)	18 / 284 (6.34%)	30 / 406 (7.39%)	7 / 137 (5.11%)
occurrences all number	14	21	35	7
Vomiting
subjects affected / exposed	4 / 202 (1.98%)	3 / 284 (1.06%)	7 / 406 (1.72%)	4 / 137 (2.92%)
occurrences all number	5	4	9	4
Skin and subcutaneous tissue disorders
Ingrowing nail
subjects affected / exposed	0 / 202 (0.00%)	0 / 284 (0.00%)	0 / 406 (0.00%)	3 / 137 (2.19%)
occurrences all number	0	0	0	4
Psoriasis
subjects affected / exposed	11 / 202 (5.45%)	15 / 284 (5.28%)	26 / 406 (6.40%)	3 / 137 (2.19%)
occurrences all number	14	15	29	3
Rash
subjects affected / exposed	5 / 202 (2.48%)	2 / 284 (0.70%)	7 / 406 (1.72%)	1 / 137 (0.73%)
occurrences all number	7	2	9	1
Skin lesion
subjects affected / exposed	1 / 202 (0.50%)	6 / 284 (2.11%)	7 / 406 (1.72%)	1 / 137 (0.73%)
occurrences all number	1	6	7	1
Renal and urinary disorders
Haematuria
subjects affected / exposed	0 / 202 (0.00%)	4 / 284 (1.41%)	4 / 406 (0.99%)	3 / 137 (2.19%)
occurrences all number	0	4	4	3
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	17 / 202 (8.42%)	23 / 284 (8.10%)	40 / 406 (9.85%)	1 / 137 (0.73%)
occurrences all number	25	35	60	1
Arthritis
subjects affected / exposed	1 / 202 (0.50%)	7 / 284 (2.46%)	8 / 406 (1.97%)	1 / 137 (0.73%)
occurrences all number	1	7	8	1
Back pain
subjects affected / exposed	17 / 202 (8.42%)	24 / 284 (8.45%)	41 / 406 (10.10%)	1 / 137 (0.73%)
occurrences all number	24	28	52	1
Muscle spasms
subjects affected / exposed	5 / 202 (2.48%)	4 / 284 (1.41%)	9 / 406 (2.22%)	1 / 137 (0.73%)
occurrences all number	5	4	9	1
Musculoskeletal pain
subjects affected / exposed	0 / 202 (0.00%)	6 / 284 (2.11%)	6 / 406 (1.48%)	0 / 137 (0.00%)
occurrences all number	0	7	7	0
Myalgia
subjects affected / exposed	2 / 202 (0.99%)	2 / 284 (0.70%)	4 / 406 (0.99%)	3 / 137 (2.19%)
occurrences all number	2	2	4	3
Osteoarthritis
subjects affected / exposed	0 / 202 (0.00%)	14 / 284 (4.93%)	14 / 406 (3.45%)	0 / 137 (0.00%)
occurrences all number	0	19	19	0
Pain in extremity
subjects affected / exposed	5 / 202 (2.48%)	5 / 284 (1.76%)	10 / 406 (2.46%)	0 / 137 (0.00%)
occurrences all number	5	5	10	0
Psoriatic arthropathy
subjects affected / exposed	20 / 202 (9.90%)	21 / 284 (7.39%)	41 / 406 (10.10%)	5 / 137 (3.65%)
occurrences all number	23	25	48	5
Infections and infestations
Bronchitis
subjects affected / exposed	11 / 202 (5.45%)	23 / 284 (8.10%)	34 / 406 (8.37%)	6 / 137 (4.38%)
occurrences all number	15	26	41	7
Conjunctivitis
subjects affected / exposed	4 / 202 (1.98%)	9 / 284 (3.17%)	13 / 406 (3.20%)	1 / 137 (0.73%)
occurrences all number	5	11	16	1
Cystitis
subjects affected / exposed	6 / 202 (2.97%)	5 / 284 (1.76%)	11 / 406 (2.71%)	1 / 137 (0.73%)
occurrences all number	7	5	12	1
Ear infection
subjects affected / exposed	1 / 202 (0.50%)	6 / 284 (2.11%)	7 / 406 (1.72%)	1 / 137 (0.73%)
occurrences all number	1	10	11	1
Gastroenteritis
subjects affected / exposed	10 / 202 (4.95%)	10 / 284 (3.52%)	20 / 406 (4.93%)	1 / 137 (0.73%)
occurrences all number	12	10	22	1
Influenza
subjects affected / exposed	12 / 202 (5.94%)	16 / 284 (5.63%)	26 / 406 (6.40%)	3 / 137 (2.19%)
occurrences all number	15	17	32	4
Lower respiratory tract infection
subjects affected / exposed	6 / 202 (2.97%)	4 / 284 (1.41%)	10 / 406 (2.46%)	0 / 137 (0.00%)
occurrences all number	11	4	15	0
Nasopharyngitis
subjects affected / exposed	44 / 202 (21.78%)	63 / 284 (22.18%)	105 / 406 (25.86%)	16 / 137 (11.68%)
occurrences all number	59	101	160	20
Oral candidiasis
subjects affected / exposed	5 / 202 (2.48%)	6 / 284 (2.11%)	11 / 406 (2.71%)	0 / 137 (0.00%)
occurrences all number	17	12	29	0
Oral herpes
subjects affected / exposed	4 / 202 (1.98%)	8 / 284 (2.82%)	12 / 406 (2.96%)	1 / 137 (0.73%)
occurrences all number	4	14	18	1
Otitis media
subjects affected / exposed	0 / 202 (0.00%)	6 / 284 (2.11%)	6 / 406 (1.48%)	0 / 137 (0.00%)
occurrences all number	0	6	6	0
Pharyngitis
subjects affected / exposed	4 / 202 (1.98%)	8 / 284 (2.82%)	12 / 406 (2.96%)	1 / 137 (0.73%)
occurrences all number	4	8	12	1
Respiratory tract infection
subjects affected / exposed	6 / 202 (2.97%)	13 / 284 (4.58%)	18 / 406 (4.43%)	0 / 137 (0.00%)
occurrences all number	10	18	28	0
Respiratory tract infection viral
subjects affected / exposed	0 / 202 (0.00%)	5 / 284 (1.76%)	5 / 406 (1.23%)	3 / 137 (2.19%)
occurrences all number	0	6	6	3
Rhinitis
subjects affected / exposed	5 / 202 (2.48%)	7 / 284 (2.46%)	12 / 406 (2.96%)	0 / 137 (0.00%)
occurrences all number	5	8	13	0
Sinusitis
subjects affected / exposed	10 / 202 (4.95%)	12 / 284 (4.23%)	22 / 406 (5.42%)	4 / 137 (2.92%)
occurrences all number	12	14	26	4
Tonsillitis
subjects affected / exposed	4 / 202 (1.98%)	14 / 284 (4.93%)	18 / 406 (4.43%)	1 / 137 (0.73%)
occurrences all number	4	15	19	1
Upper respiratory tract infection
subjects affected / exposed	27 / 202 (13.37%)	35 / 284 (12.32%)	61 / 406 (15.02%)	7 / 137 (5.11%)
occurrences all number	40	59	99	7
Urinary tract infection
subjects affected / exposed	13 / 202 (6.44%)	20 / 284 (7.04%)	31 / 406 (7.64%)	2 / 137 (1.46%)
occurrences all number	16	28	44	2
Viral upper respiratory tract infection
subjects affected / exposed	5 / 202 (2.48%)	4 / 284 (1.41%)	9 / 406 (2.22%)	1 / 137 (0.73%)
occurrences all number	8	5	13	1
Metabolism and nutrition disorders
Dyslipidaemia
subjects affected / exposed	6 / 202 (2.97%)	3 / 284 (1.06%)	9 / 406 (2.22%)	0 / 137 (0.00%)
occurrences all number	6	3	9	0
Vitamin D deficiency
subjects affected / exposed	1 / 202 (0.50%)	6 / 284 (2.11%)	7 / 406 (1.72%)	0 / 137 (0.00%)
occurrences all number	1	6	7	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

17 Dec 2014

Amendment 1 was primarily issued for the following reasons: To expand the statistical hierarchy (primary plus ranked secondary variables) to include endpoints relevant to determining the overall therapeutic value of a therapy for PsA.

26 May 2016

Amendment 2 was primarily issued for the following reasons: a) Allowing dose escalation of secukinumab administered s.c. every 4 weeks from 150 mg to 300 mg b) Clarification on the duration of contraception

19 Sep 2016

Amendment 3 was primarily issued to include the correction of typographical and formatting errors and editorial changes for increased clarity of the text.

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

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Proportion of patients achieving American College of Rheumatology 20 (ACR20) response criteria on secukinumab versus placebo at Week 24

Primary: Proportion of patients achieving American College of Rheumatology 20 (ACR20) response criteria on secukinumab versus placebo at Week 24

Secondary: Proportion of patients achieving American College of Rheumatology 50 (ACR50) response criteria on secukinumab versus placebo at Week 24

Secondary: Proportion of patients achieving American College of Rheumatology 50 (ACR50) response criteria on secukinumab versus placebo at Week 24

Secondary: Change from baseline in Disease Activity Score for 28 joints (DAS28-CRP) (utilizing hsCRP) in subjects treated with secukinumab versus placebo at Week 24

Secondary: Change from baseline in Disease Activity Score for 28 joints (DAS28-CRP) (utilizing hsCRP) in subjects treated with secukinumab versus placebo at Week 24

Secondary: Proportion of subjects achieving a Psoriatic Area and Severity Index 75 (PASI75) response in subjects on secukinumab versus placebo at Week 24

Secondary: Proportion of subjects achieving a Psoriatic Area and Severity Index 75 (PASI75) response in subjects on secukinumab versus placebo at Week 24

Secondary: Change from baseline in Physical function component of the short-form health survey (SF-36-PCS) in subjects treated with secukinumab versus placebo at Week 24

Secondary: Change from baseline in Physical function component of the short-form health survey (SF-36-PCS) in subjects treated with secukinumab versus placebo at Week 24

Secondary: Psoriatic Area and Severity Index 90 (PASI90) response in subjects treated with secukinumab versus placebo at Week 24

Secondary: Psoriatic Area and Severity Index 90 (PASI90) response in subjects treated with secukinumab versus placebo at Week 24

Secondary: Change from baseline in Health Assessment Questionnaire – Disability Index (HAQ-DI score) in subjects treated with secukinumab versus placebo at Week 24

Secondary: Change from baseline in Health Assessment Questionnaire – Disability Index (HAQ-DI score) in subjects treated with secukinumab versus placebo at Week 24

Secondary: Overall safety and tolerability

Secondary: Overall safety and tolerability

Secondary: Proportion of patients with Dactylitis at Week 24 in the subset of patients who had dactylitis at Baseline

Secondary: Proportion of patients with Dactylitis at Week 24 in the subset of patients who had dactylitis at Baseline

Secondary: Proportion of patients with Enthesitis at Week 24 in the subset of patients who had enthesitis at Baseline

Secondary: Proportion of patients with Enthesitis at Week 24 in the subset of patients who had enthesitis at Baseline

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA