Intravitreal Aflibercept Injection in Vision Impairment D... | NCT01331681

ID	Type	Description	Link
2010-022364-12	EudraCT Number

Name	Class
Regeneron Pharmaceuticals	INDUSTRY

Label	Type	Description	Intervention Names
Intravitreal Aflibercept Injection 2Q4	Experimental	Participants received 2mg Intravitreal aflibercept injection (IAI) (EYLEA, VEGF Trap-Eye, BAY86-5321) every 4 weeks (2Q4).	Biological: VEGF Trap-Eye (BAY86-5321)
Intravitreal Aflibercept Injection 2Q8	Experimental	Participants received 2mg Intravitreal aflibercept injection (IAI) (EYLEA, VEGF Trap-Eye, BAY86-5321) every 4 weeks for 5 visits followed by injections every 8 weeks (2Q8).	Biological: VEGF Trap-Eye (BAY86-5321)
Macular Laser Photocoagulation (Control)	Active Comparator	Participants received laser treatment at baseline and as needed at visits at which laser retreatment criteria were met, but no more frequently than every 12 weeks.	Procedure: Macular Laser Photocoagulation (Control)

Name	Type	Description	Arm Group Labels	Other Names
VEGF Trap-Eye (BAY86-5321)	Biological	Participants received 2mg Intravitreal aflibercept injection (IAI) (EYLEA, VEGF Trap-Eye, BAY86-5321) every 4 weeks (2Q4).	Intravitreal Aflibercept Injection 2Q4

Measure	Description	Time Frame
Change From Baseline in BCVA (Best Corrected Visual Acuity) as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 52 - Last Observation Carried Forward (LOCF)	Visual function of the study eye was assessed using the ETDRS protocol. A higher score represents better functioning.	Baseline up to Week 52

Measure	Description	Time Frame
Percentage of Participants Who Gained at Least 10 Letters in BCVA as Measured by ETDRS Letter Score Compared With Baseline at Week 52 - LOCF	Visual function of the study eye was assessed using the ETDRS protocol. A higher score represents better functioning.	Baseline up to Week 52
Percentage of Participants Who Gained at Least 15 Letters in BCVA as Measured by ETDRS Letter Score Compared With Baseline at Week 52 - LOCF

Name	Affiliation	Role
Bayer Study Director	Bayer	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
		Sydney	New South Wales	2000	Australia

PubMed Identifier	Type	Citation	Retractions
37007927	Background	Nanegrungsunk O, Gu SZ, Bressler SB, Du W, Amer F, Moini H, Bressler NM. Correlation of Change in Macular Thickness With Change in Visual Acuity in Diabetic Macular Edema: Post Hoc Analysis of VISTA and VIVID Trials. J Vitreoretin Dis. 2022 Jul 27;6(4):284-289. doi: 10.1177/24741264221099429. eCollection 2022 Jul-Aug.
35843487

ID	Title	Description
FG000	Intravitreal Aflibercept Injection 2Q4	Participants received 2mg Intravitreal aflibercept injection (IAI) (EYLEA, VEGF [vascular endothelial growth factor] Trap-Eye, BAY86-5321) every 4 weeks (2Q4).
FG001	Intravitreal Aflibercept Injection 2Q8

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in BCVA (Best Corrected Visual Acuity) as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 52 - Last Observation Carried Forward (LOCF)

Visual function of the study eye was assessed using the ETDRS protocol. A higher score represents better functioning.

Full analysis set (FAS) included all randomized participants who received any study treatment, had a baseline measurement of BCVA, and had at least 1 post-baseline assessment of BCVA.

Posted

Mean

Standard Deviation

Letters correctly read

Baseline up to Week 52

ID	Title	Description
OG000	Intravitreal Aflibercept Injection 2Q4	Participants received 2mg Intravitreal aflibercept injection (IAI) (EYLEA, VEGF Trap-Eye, BAY86-5321) every 4 weeks (2Q4).
OG001	Intravitreal Aflibercept Injection 2Q8	Participants received 2mg Intravitreal aflibercept injection (IAI) (EYLEA, VEGF Trap-Eye, BAY86-5321) every 4 weeks for 5 visits followed by injections every 8 weeks (2Q8).
OG002	Control	Participants received laser treatment at baseline and as needed at visits at which laser retreatment criteria were met, but no more frequently than every 12 weeks.

Units	Counts
Participants	OG000136 OG001135 OG002132

Title

Denominators

Categories

Title	Measurements
	OG00010.5± 9.55 OG00110.7± 9.32 OG0021.2± 10.65

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG002	Hypothesis: Mean change identical in both groups	ANCOVA	Treatment group and geographic region (Japan vs. Non-Japan) as factors and baseline value as covariate.	<0.0001	Significance level alpha=0.025 for two sided test to adjust for multiplicity. Since this p-value was below the significance level of 0.025, the fixed sequence testing did continue with the first secondary endpoint.	Mean Difference (Final Values)	9.3			2-Sided	97.5	6.5	12.0			Least square (LS) mean difference from ANCOVA. The estimate is calculated as EYLEA minus Laser. A positive value indicates a result in favor of EYLEA.

Secondary

Percentage of Participants Who Gained at Least 10 Letters in BCVA as Measured by ETDRS Letter Score Compared With Baseline at Week 52 - LOCF

Visual function of the study eye was assessed using the ETDRS protocol. A higher score represents better functioning.

FAS.

Posted

Number

Percentage of participants

Baseline up to Week 52

ID	Title	Description
OG000	Intravitreal Aflibercept Injection 2Q4	Participants received 2mg Intravitreal aflibercept injection (IAI) (EYLEA, VEGF Trap-Eye, BAY86-5321) every 4 weeks (2Q4).
OG001	Intravitreal Aflibercept Injection 2Q8	Participants received 2mg Intravitreal aflibercept injection (IAI) (EYLEA, VEGF Trap-Eye, BAY86-5321) every 4 weeks for 5 visits followed by injections every 8 weeks (2Q8).
OG002	Control	Participants received laser treatment at baseline and as needed at visits at which laser retreatment criteria were met, but no more frequently than every 12 weeks.

Units

Secondary

Percentage of Participants Who Gained at Least 15 Letters in BCVA as Measured by ETDRS Letter Score Compared With Baseline at Week 52 - LOCF

Visual function of the study eye was assessed using the ETDRS protocol. A higher score represents better functioning.

FAS.

Posted

Number

Percentage of participants

Baseline up to Week 52

ID	Title	Description
OG000	Intravitreal Aflibercept Injection 2Q4	Participants received 2mg Intravitreal aflibercept injection (IAI) (EYLEA, VEGF Trap-Eye, BAY86-5321) every 4 weeks (2Q4).
OG001	Intravitreal Aflibercept Injection 2Q8	Participants received 2mg Intravitreal aflibercept injection (IAI) (EYLEA, VEGF Trap-Eye, BAY86-5321) every 4 weeks for 5 visits followed by injections every 8 weeks (2Q8).
OG002	Control	Participants received laser treatment at baseline and as needed at visits at which laser retreatment criteria were met, but no more frequently than every 12 weeks.

Units

Secondary

Percentage of Participants With a ≥2-step Improvement From Baseline in the ETDRS DRSS (Diabetic Retinopathy Severity Score) as Assessed by FP (Fundus Photography) at Week 52 - LOCF

Baseline ETDRS DRSS: None (level 10); Mild to moderate nonproliferative DR (levels 14, 15, 20, 35, and 43); Moderately severe/severe nonproliferative DR (levels 47 and 53); Mild/moderate/high-risk/advanced proliferative DR (levels 61, 65, 71,75, 81, and 85)

Full-Analysis Set with assessment for this outcome measure.

Posted

Number

Percentage of participants

Baseline up to Week 52

ID	Title	Description
OG000	Intravitreal Aflibercept Injection 2Q4	Participants received 2mg Intravitreal aflibercept injection (IAI) (EYLEA, VEGF Trap-Eye, BAY86-5321) every 4 weeks (2Q4).
OG001	Intravitreal Aflibercept Injection 2Q8	Participants received 2mg Intravitreal aflibercept injection (IAI) (EYLEA, VEGF Trap-Eye, BAY86-5321) every 4 weeks for 5 visits followed by injections every 8 weeks (2Q8).
OG002	Control	Participants received laser treatment at baseline and as needed at visits at which laser retreatment criteria were met, but no more frequently than every 12 weeks.

Secondary

Change From Baseline in Central Retinal Thickness (CRT) at Week 52 as Assessed on Optical Coherence Tomography (OCT) - LOCF

Full-Analysis Set with assessment for this outcome measure.

Posted

Mean

Standard Deviation

micrometer

Baseline up to Week 52

ID	Title	Description
OG000	Intravitreal Aflibercept Injection 2Q4	Participants received 2mg Intravitreal aflibercept injection (IAI) (EYLEA, VEGF Trap-Eye, BAY86-5321) every 4 weeks (2Q4).
OG001	Intravitreal Aflibercept Injection 2Q8	Participants received 2mg Intravitreal aflibercept injection (IAI) (EYLEA, VEGF Trap-Eye, BAY86-5321) every 4 weeks for 5 visits followed by injections every 8 weeks (2Q8).
OG002	Control	Participants received laser treatment at baseline and as needed at visits at which laser retreatment criteria were met, but no more frequently than every 12 weeks.

Units	Counts
Participants

Secondary

Change From Baseline in National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Near Activities Subscale at Week 52 - LOCF

The NEI VFQ-25 total score ranges from 0-100 with a score of 0 being the worst outcome and 100 being the best outcome. The NEI VFQ questionnaire is organized as a collection of subscales that are all scored from 0-100. Near activities are defined as reading ordinary print in newspapers, performing work or hobbies requiring near vision, or finding something on a crowded shelf.

Full-Analysis Set with assessment for this outcome measure.

Posted

Mean

Standard Deviation

Scores on a scale

Baseline up to Week 52

ID	Title	Description
OG000	Intravitreal Aflibercept Injection 2Q4	Participants received 2mg Intravitreal aflibercept injection (IAI) (EYLEA, VEGF Trap-Eye, BAY86-5321) every 4 weeks (2Q4).
OG001	Intravitreal Aflibercept Injection 2Q8	Participants received 2mg Intravitreal aflibercept injection (IAI) (EYLEA, VEGF Trap-Eye, BAY86-5321) every 4 weeks for 5 visits followed by injections every 8 weeks (2Q8).
OG002	Control	Participants received laser treatment at baseline and as needed at visits at which laser retreatment criteria were met, but no more frequently than every 12 weeks.

Secondary

Change From Baseline in National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Distance Activities Subscale at Week 52 - LOCF

The NEI VFQ-25 total score ranges from 0-100 with a score of 0 being the worst outcome and 100 being the best outcome. The NEI VFQ questionnaire is organized as a collection of subscales that are all scored from 0-100. Distance activities are defined as reading street signs or names on stores, and going down stairs, steps, or curbs.

Full-Analysis Set with assessment for this outcome measure.

Posted

Mean

Standard Deviation

Scores on a scale

Baseline up to Week 52

ID	Title	Description
OG000	Intravitreal Aflibercept Injection 2Q4	Participants received 2mg Intravitreal aflibercept injection (IAI) (EYLEA, VEGF Trap-Eye, BAY86-5321) every 4 weeks (2Q4).
OG001	Intravitreal Aflibercept Injection 2Q8	Participants received 2mg Intravitreal aflibercept injection (IAI) (EYLEA, VEGF Trap-Eye, BAY86-5321) every 4 weeks for 5 visits followed by injections every 8 weeks (2Q8).
OG002	Control	Participants received laser treatment at baseline and as needed at visits at which laser retreatment criteria were met, but no more frequently than every 12 weeks.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0021 events1 affected133 at risk
Immune thrombocytopenic purpura	Blood and lymphatic system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0002 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA (18.0)	Non-systematic Assessment	EG0002 events2 affected136 at risk EG0010 events0 affected135 at risk EG0023 events3 affected133 at risk
Angina unstable	Cardiac disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Arrhythmia	Cardiac disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Atrioventricular block complete	Cardiac disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Bundle branch block right	Cardiac disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Cardiac disorder	Cardiac disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Cardiac failure	Cardiac disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0012 events2 affected135 at risk EG0022 events2 affected133 at risk
Cardiac failure acute	Cardiac disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Cardiac failure chronic	Cardiac disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0022 events1 affected133 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Cardiac sarcoidosis	Cardiac disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Cardiac valve disease	Cardiac disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Cardiogenic shock	Cardiac disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Coronary artery disease	Cardiac disorders	MedDRA (18.0)	Non-systematic Assessment	EG0003 events2 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Coronary artery stenosis	Cardiac disorders	MedDRA (18.0)	Non-systematic Assessment	EG0002 events2 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Hypertensive heart disease	Cardiac disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Ischaemic cardiomyopathy	Cardiac disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Left ventricular failure	Cardiac disorders	MedDRA (18.0)	Non-systematic Assessment	EG0002 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Mitral valve stenosis	Cardiac disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Myocardial infarction	Cardiac disorders	MedDRA (18.0)	Non-systematic Assessment	EG0004 events4 affected136 at risk EG0011 events1 affected135 at risk EG0021 events1 affected133 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Ventricular arrhythmia	Cardiac disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Ventricular tachycardia	Cardiac disorders	MedDRA (18.0)	Non-systematic Assessment	EG0002 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Deafness	Ear and labyrinth disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Vertigo	Ear and labyrinth disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Toxic nodular goitre	Endocrine disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Cataract	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG0008 events5 affected136 at risk EG00111 events7 affected135 at risk EG0022 events2 affected133 at risk
Cataract subcapsular	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0012 events2 affected135 at risk EG0020 events0 affected133 at risk
Diabetic retinopathy	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0022 events2 affected133 at risk
Iridocyclitis	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Macular degeneration	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Macular fibrosis	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Macular hole	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Optic atrophy	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Posterior capsule opacification	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Retinal artery occlusion	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Retinal detachment	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0012 events2 affected135 at risk EG0021 events1 affected133 at risk
Retinal exudates	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Retinal neovascularisation	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0024 events3 affected133 at risk
Retinal vascular disorder	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0022 events1 affected133 at risk
Retinopathy proliferative	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Vitreous haemorrhage	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG0005 events4 affected136 at risk EG0011 events1 affected135 at risk EG0024 events2 affected133 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Colitis ischaemic	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Enterocolitis	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Gastric ulcer	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Ileus	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0012 events2 affected135 at risk EG0020 events0 affected133 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Reflux gastritis	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Chest pain	General disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Death	General disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Device failure	General disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0022 events1 affected133 at risk
Generalised oedema	General disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0012 events1 affected135 at risk EG0020 events0 affected133 at risk
Injection site injury	General disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Oedema peripheral	General disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Hepatic cirrhosis	Hepatobiliary disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Cellulitis	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0012 events2 affected135 at risk EG0022 events2 affected133 at risk
Cholecystitis infective	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Endophthalmitis	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Gangrene	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Gastroenteritis	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Infected dermal cyst	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Infected skin ulcer	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Osteomyelitis	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Pilonidal cyst	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Pneumonia	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0013 events3 affected135 at risk EG0020 events0 affected133 at risk
Pyelonephritis	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Salmonellosis	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Sepsis	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0021 events1 affected133 at risk
Urinary tract infection	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0022 events1 affected133 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Brain contusion	Injury, poisoning and procedural complications	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Brain herniation	Injury, poisoning and procedural complications	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Fracture	Injury, poisoning and procedural complications	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Head injury	Injury, poisoning and procedural complications	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA (18.0)	Non-systematic Assessment	EG0003 events3 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Joint dislocation	Injury, poisoning and procedural complications	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Lower limb fracture	Injury, poisoning and procedural complications	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Meniscus injury	Injury, poisoning and procedural complications	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Spinal fracture	Injury, poisoning and procedural complications	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Thermal burn	Injury, poisoning and procedural complications	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Tibia fracture	Injury, poisoning and procedural complications	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Traumatic arthrosis	Injury, poisoning and procedural complications	MedDRA (18.0)	Non-systematic Assessment	EG0002 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Traumatic fracture	Injury, poisoning and procedural complications	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Catheterisation cardiac	Investigations	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Electrocardiogram ST segment depression	Investigations	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Visual acuity tests abnormal	Investigations	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA (18.0)	Non-systematic Assessment	EG0002 events1 affected136 at risk EG0012 events2 affected135 at risk EG0022 events1 affected133 at risk
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Fluid retention	Metabolism and nutrition disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0012 events2 affected135 at risk EG0022 events2 affected133 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Ketoacidosis	Metabolism and nutrition disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Type 2 diabetes mellitus	Metabolism and nutrition disorders	MedDRA (18.0)	Non-systematic Assessment	EG0002 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Arthropathy	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Lumbar spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0022 events2 affected133 at risk
Metatarsalgia	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Musculoskeletal disorder	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0002 events2 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Polymyalgia rheumatica	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0021 events1 affected133 at risk
Rotator cuff syndrome	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Spinal column stenosis	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0012 events1 affected135 at risk EG0020 events0 affected133 at risk
Spinal pain	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Spondylolisthesis	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Synovitis	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Tenosynovitis stenosans	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Adenocarcinoma of colon	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Adrenal neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Anaplastic astrocytoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
B-cell lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Bladder neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Lung neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Metastases to liver	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0021 events1 affected133 at risk
Metastases to lung	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0021 events1 affected133 at risk
Neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Pancreatic carcinoma stage IV	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Prostate cancer stage I	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Prostate cancer stage III	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Renal neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Non-systematic Assessment	EG0002 events2 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Brain stem infarction	Nervous system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Cauda equina syndrome	Nervous system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Cerebral atrophy	Nervous system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Cerebral haematoma	Nervous system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0004 events4 affected136 at risk EG0011 events1 affected135 at risk EG0021 events1 affected133 at risk
Ischaemic stroke	Nervous system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0002 events2 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Loss of consciousness	Nervous system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Nerve compression	Nervous system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Peripheral sensorimotor neuropathy	Nervous system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Syncope	Nervous system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Depression	Psychiatric disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0022 events1 affected133 at risk
Suicide attempt	Psychiatric disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Chronic kidney disease	Renal and urinary disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Renal artery stenosis	Renal and urinary disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Renal failure	Renal and urinary disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0012 events2 affected135 at risk EG0020 events0 affected133 at risk
Renal impairment	Renal and urinary disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0012 events1 affected135 at risk EG0020 events0 affected133 at risk
Stress urinary incontinence	Renal and urinary disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0022 events2 affected133 at risk
Uterine polyp	Reproductive system and breast disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Uterine prolapse	Reproductive system and breast disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Hydrothorax	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Sleep apnoea syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Dermal cyst	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Diabetic foot	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0002 events1 affected136 at risk EG0010 events0 affected135 at risk EG0022 events2 affected133 at risk
Psoriasis	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0023 events2 affected133 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0022 events2 affected133 at risk
Arteriovenous shunt operation	Surgical and medical procedures	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Cataract operation	Surgical and medical procedures	MedDRA (18.0)	Non-systematic Assessment	EG0003 events3 affected136 at risk EG0011 events1 affected135 at risk EG0023 events2 affected133 at risk
Hip arthroplasty	Surgical and medical procedures	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Osteosynthesis	Surgical and medical procedures	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Peripheral artery bypass	Surgical and medical procedures	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Radical prostatectomy	Surgical and medical procedures	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Transurethral prostatectomy	Surgical and medical procedures	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Vitrectomy	Surgical and medical procedures	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Arterial haemorrhage	Vascular disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Arteriosclerosis	Vascular disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Circulatory collapse	Vascular disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Deep vein thrombosis	Vascular disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0020 events0 affected133 at risk
Hypertension	Vascular disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0011 events1 affected135 at risk EG0020 events0 affected133 at risk
Lymphoedema	Vascular disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Peripheral arterial occlusive disease	Vascular disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0012 events2 affected135 at risk EG0023 events3 affected133 at risk
Peripheral artery stenosis	Vascular disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected135 at risk EG0021 events1 affected133 at risk
Peripheral ischaemia	Vascular disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected135 at risk EG0023 events1 affected133 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0006 events6 affected136 at risk EG0013 events3 affected135 at risk EG0028 events8 affected133 at risk
Cataract	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG00043 events31 affected136 at risk EG00137 events26 affected135 at risk EG00229 events17 affected133 at risk
Cataract cortical	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG00012 events7 affected136 at risk EG0017 events6 affected135 at risk EG0023 events1 affected133 at risk
Cataract subcapsular	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG00016 events11 affected136 at risk EG0016 events5 affected135 at risk EG0024 events4 affected133 at risk
Conjunctival haemorrhage	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG00059 events43 affected136 at risk EG00158 events39 affected135 at risk EG00226 events17 affected133 at risk
Conjunctival hyperaemia	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG00010 events8 affected136 at risk EG0015 events3 affected135 at risk EG00215 events9 affected133 at risk
Corneal erosion	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG00011 events9 affected136 at risk EG00110 events8 affected135 at risk EG00216 events7 affected133 at risk
Cystoid macular oedema	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG00018 events10 affected136 at risk EG00167 events20 affected135 at risk EG00251 events18 affected133 at risk
Diabetic retinal oedema	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG00049 events33 affected136 at risk EG00144 events23 affected135 at risk EG00225 events18 affected133 at risk
Eye pain	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG00034 events15 affected136 at risk EG00119 events10 affected135 at risk EG00215 events10 affected133 at risk
Macular fibrosis	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG00013 events10 affected136 at risk EG00117 events12 affected135 at risk EG00214 events11 affected133 at risk
Macular oedema	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG00041 events21 affected136 at risk EG00131 events20 affected135 at risk EG00246 events22 affected133 at risk
Ocular hyperaemia	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG00012 events5 affected136 at risk EG0019 events7 affected135 at risk EG0025 events4 affected133 at risk
Ocular hypertension	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG00021 events10 affected136 at risk EG0019 events4 affected135 at risk EG0027 events6 affected133 at risk
Posterior capsule opacification	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG00015 events10 affected136 at risk EG00115 events12 affected135 at risk EG00218 events10 affected133 at risk
Punctate keratitis	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG00013 events7 affected136 at risk EG00119 events11 affected135 at risk EG00214 events8 affected133 at risk
Retinal aneurysm	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG00026 events14 affected136 at risk EG00126 events12 affected135 at risk EG00216 events9 affected133 at risk
Retinal exudates	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG00038 events20 affected136 at risk EG00149 events22 affected135 at risk EG00232 events15 affected133 at risk
Retinal haemorrhage	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG00035 events21 affected136 at risk EG00164 events25 affected135 at risk EG00263 events21 affected133 at risk
Retinal vascular disorder	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG00020 events9 affected136 at risk EG00113 events8 affected135 at risk EG00210 events5 affected133 at risk
Visual acuity reduced	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG00064 events33 affected136 at risk EG00181 events33 affected135 at risk EG00257 events30 affected133 at risk
Vitreous detachment	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG00012 events9 affected136 at risk EG00111 events10 affected135 at risk EG0027 events5 affected133 at risk
Vitreous floaters	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG00014 events13 affected136 at risk EG0017 events5 affected135 at risk EG0024 events4 affected133 at risk
Vitreous haemorrhage	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG00014 events7 affected136 at risk EG00111 events11 affected135 at risk EG00212 events8 affected133 at risk
Bronchitis	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG00016 events12 affected136 at risk EG0015 events5 affected135 at risk EG00210 events9 affected133 at risk
Conjunctivitis	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG00016 events14 affected136 at risk EG00120 events13 affected135 at risk EG00210 events8 affected133 at risk
Influenza	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG00010 events7 affected136 at risk EG00111 events11 affected135 at risk EG00216 events13 affected133 at risk
Nasopharyngitis	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG00067 events38 affected136 at risk EG00169 events39 affected135 at risk EG00262 events34 affected133 at risk
Urinary tract infection	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0008 events6 affected136 at risk EG00122 events11 affected135 at risk EG00211 events6 affected133 at risk
Blood creatinine increased	Investigations	MedDRA (18.0)	Non-systematic Assessment	EG0008 events7 affected136 at risk EG0016 events6 affected135 at risk EG0025 events5 affected133 at risk
Blood glucose increased	Investigations	MedDRA (18.0)	Non-systematic Assessment	EG00013 events10 affected136 at risk EG0018 events7 affected135 at risk EG00210 events8 affected133 at risk
Blood urea increased	Investigations	MedDRA (18.0)	Non-systematic Assessment	EG0008 events6 affected136 at risk EG00110 events10 affected135 at risk EG0027 events6 affected133 at risk
Glycosylated haemoglobin increased	Investigations	MedDRA (18.0)	Non-systematic Assessment	EG00015 events12 affected136 at risk EG00112 events11 affected135 at risk EG00211 events11 affected133 at risk
Intraocular pressure increased	Investigations	MedDRA (18.0)	Non-systematic Assessment	EG00077 events28 affected136 at risk EG00151 events18 affected135 at risk EG00232 events16 affected133 at risk
Visual acuity tests abnormal	Investigations	MedDRA (18.0)	Non-systematic Assessment	EG00035 events19 affected136 at risk EG00163 events22 affected135 at risk EG00249 events32 affected133 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA (18.0)	Non-systematic Assessment	EG0006 events6 affected136 at risk EG00112 events10 affected135 at risk EG00210 events9 affected133 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0005 events4 affected136 at risk EG0013 events3 affected135 at risk EG00211 events11 affected133 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected136 at risk EG0019 events9 affected135 at risk EG0021 events1 affected133 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG00010 events7 affected136 at risk EG0016 events6 affected135 at risk EG00210 events7 affected133 at risk
Hypertension	Vascular disorders	MedDRA (18.0)	Non-systematic Assessment	EG00032 events23 affected136 at risk EG00137 events25 affected135 at risk EG00241 events24 affected133 at risk
Dry eye	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG0009 events5 affected136 at risk EG0017 events5 affected135 at risk EG00213 events8 affected133 at risk

ID	Term
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases
D008268	Macular Degeneration
D012162	Retinal Degeneration
D012164	Retinal Diseases
D005128	Eye Diseases

ID	Title	Description
BG000	Intravitreal Aflibercept Injection 2Q4	Participants received 2mg Intravitreal aflibercept injection (IAI) (EYLEA, VEGF Trap-Eye, BAY86-5321) every 4 weeks (2Q4).
BG001	Intravitreal Aflibercept Injection 2Q8	Participants received 2mg Intravitreal aflibercept injection (IAI) (EYLEA, VEGF Trap-Eye, BAY86-5321) every 4 weeks for 5 visits followed by injections every 8 weeks (2Q8).
BG002	Control	Participants received laser treatment at baseline and as needed at visits at which laser retreatment criteria were met, but no more frequently than every 12 weeks.
BG003	Total	Total of all reporting groups

ID	Title	Description	Serious Events (Affected)	Other Events (Affected)	Other Events (At Risk)
EG000	Intravitreal Aflibercept Injection 2Q4	Participants received 2mg Intravitreal aflibercept injection (IAI) (EYLEA, VEGF Trap-Eye, BAY86-5321) every 4 weeks (2Q4).	63	117	136
EG001	Intravitreal Aflibercept Injection 2Q8	Participants received 2mg Intravitreal aflibercept injection (IAI) (EYLEA, VEGF Trap-Eye, BAY86-5321) every 4 weeks for 5 visits followed by injections every 8 weeks (2Q8).	60	122	135
EG002	Macular Laser Photocoagulation (Control)	Participants received laser treatment at baseline and as needed at visits at which laser retreatment criteria were met, but no more frequently than every 12 weeks. During year 3 laser patients could receive IAI as needed (PRN) .	51	113	133