Managing Neovascular (Known as "Wet") Age-related Macular... | NCT02581891

NCT02581891

ID	Type	Description	Link
2014-003132-39	EudraCT Number

Status Module

Name	Class
Regeneron Pharmaceuticals	INDUSTRY

Label	Type	Description	Intervention Names
Early-start T&E / Arm 1	Experimental	Early-start T&E arm: test group, early treatment individualization	Drug: Eylea (Intravitreal Aflibercept, VEGF Trap-Eye, BAY86-5321)
Late-start T&E / Arm 2	Active Comparator	Late-start T&E arm; per label, control group, treatment individualization after Year 1	Drug: Eylea (Intravitreal Aflibercept, VEGF Trap-Eye, BAY86-5321)

Name	Type	Description	Arm Group Labels	Other Names
Eylea (Intravitreal Aflibercept, VEGF Trap-Eye, BAY86-5321)	Drug	3 monthly doses followed by individualized treatment intervals of between 8 to16 weeks based on protocol-defined anatomical criteria

Measure	Description	Time Frame
Change in BCVA as Measured by the ETDRS Letter Score	BCVA (best corrected visual acuity) was measured by the ETDRS (Early Treatment Diabetic Retinopathy Study) letter score of 73 to 25 (= Acuity of 20/40 to 20/320) in the study eye at 4 meters; a higher score represents better functioning.	From Week 16 to Week 104

Measure	Description	Time Frame
Percentage of Participants Maintaining Vision (<3 Lines Loss) at Week 104 Compared With Baseline	Participants maintained 3 lines (15 letters) vision loss in BCVA (Best-corrected visual acuity) as measured by the ETDRS (Early Treatment Diabetic Retinopathy Study) letter.	at Week 104
Change in BCVA From Baseline to Week 52, Baseline to Week 104, and Week 16 to Week 52

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Men and women ≥ 50 years of age.
Active primary subfoveal CNV lesions secondary to nAMD, including juxtafoveal lesions that affect the fovea as evidenced by FA in the study eye. Patients with polypoidal choroidal vasculopathy or retinal angiomatous proliferation are eligible to participate in the study, and their condition should be captured in the eCRF.
ETDRS BCVA of 73 to 25 letters (20/40 to 20/320 Snellen equivalent) in the study eye.
The area of CNV must occupy at least 50% of the total lesion.

Exclusion Criteria:

Any prior ocular (in the study eye) or systemic treatment or surgery for nAMD, except dietary supplements or vitamins.
Any prior or concomitant therapy with another investigational agent to treat nAMD in the study eye.
Prior treatment with anti-VEGF agents as follows:
Prior treatment with anti-VEGF therapy in the study eye is not allowed
Prior treatment with anti-VEGF therapy in the fellow eye with an investigational agent (not approved, e.g. bevacizumab) within the last 3 months before the first dose in the study. Such treatment will also not be allowed during the study. Prior treatment with an approved anti-VEGF therapy in the fellow eye is allowed.
Prior systemic anti-VEGF therapy, investigational or approved, within the last 3 months before the first dose in the study, and such treatment will not be allowed during the study.
Total lesion size >12 disc areas (30.5 mm2, including blood, scars and neovascularization) as assessed by FA in the study eye.
Subretinal hemorrhages that are either 50% or more of the total lesion area, or if the blood is under the fovea and is 1 or more disc areas in size in the study eye. (If the blood is under the fovea, then the fovea must be surrounded by 270 degrees by visible CNV).
Scar or fibrosis making up >50% of the total lesion in the study eye.
Scar, fibrosis, or atrophy involving the center of the fovea in the study eye.
Presence of retinal pigment epithelial tears or rips involving the macula in the study eye.

Name	Affiliation	Role
Bayer Study Director	Bayer	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
		Strathfield	New South Wales	2135	Australia

PubMed Identifier	Type	Citation	Retractions
35821380	Result	Wolf S, Holz FG, Midena E, Souied EH, Lambrou G, Machewitz T, Allmeier H, Mitchell P; ARIES Study Investigators. Patients with Neovascular Age-Related Macular Degeneration Requiring Intensive Intravitreal Aflibercept Treatment: An ARIES Post Hoc Analysis. Ophthalmol Ther. 2022 Oct;11(5):1793-1803. doi: 10.1007/s40123-022-00541-8. Epub 2022 Jul 12.
35303285

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Early-start T&E Arm	All participants during the initiation phase received Aflibercept (Eylea, BAY86-5321) 3 doses at Weeks 0, 4, and 8 followed by one dose 2Q8 (2 mg administered every 8 weeks) at Week 16. From Week 16 to Week 104 participants randomized to Early-start T&E arm (Treat and Extend arm) received treatment in individualized intervals of between 8 to16 weeks based on anatomical criteria.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 2, 2016	Apr 21, 2020

Arm/Group Information

ID	Title	Description
BG000	Early-start T&E Arm	All participants during the initiation phase received Aflibercept (Eylea, BAY86-5321) 3 doses at Weeks 0, 4, and 8 followed by one dose 2Q8 (2 mg administered every 8 weeks) at Week 16. From Week 16 to Week 104 participants randomized to Early-start T&E arm (Treat and Extend arm) received treatment in individualized intervals of between 8 to16 weeks based on anatomical criteria.
BG001	Late-start T&E Arm	All participants during the initiation phase received Aflibercept (Eylea, BAY86-5321) 3 doses at Weeks 0, 4, and 8 followed by one dose 2Q8 (2 mg administered every 8 weeks) at Week 16. From Week 16 participants randomized to Late-start T&E arm received four 2Q8 injections. In Year 2 starting at Week 48, participants received treatment in individualized intervals of between 8 to16 weeks based on anatomical criteria.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	OG000-2.1± 11.4 OG001-0.4± 8.4

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 OG001		ANCOVA		0.0162		LS mean difference	-2.0199	Standard Error of the Mean	1.3833	2-Sided	95	-4.7470	0.7073					Non-Inferiority	The non-inferiority margin is set to 5 letters.

Secondary

Percentage of Participants Maintaining Vision (<3 Lines Loss) at Week 104 Compared With Baseline

Participants maintained 3 lines (15 letters) vision loss in BCVA (Best-corrected visual acuity) as measured by the ETDRS (Early Treatment Diabetic Retinopathy Study) letter.

PPS (Per-protocol set): all participants in the FAS (full analysis set) without any major protocol deviation.

Posted

Number

Percentage

at Week 104

ID	Title	Description
OG000	Early-start T&E Arm	All participants during the initiation phase received Aflibercept (Eylea, BAY86-5321) 3 doses at Weeks 0, 4, and 8 followed by one dose 2Q8 (2 mg administered every 8 weeks) at Week 16. From Week 16 to Week 104 participants randomized to Early-start T&E arm (Treat and Extend arm) received treatment in individualized intervals of between 8 to16 weeks based on anatomical criteria.
OG001	Late-start T&E Arm	All participants during the initiation phase received Aflibercept (Eylea, BAY86-5321) 3 doses at Weeks 0, 4, and 8 followed by one dose 2Q8 (2 mg administered every 8 weeks) at Week 16. From Week 16 participants randomized to Late-start T&E arm received four 2Q8 injections. In Year 2 starting at Week 48, participants received treatment in individualized intervals of between 8 to16 weeks based on anatomical criteria.

Secondary

Change in BCVA From Baseline to Week 52, Baseline to Week 104, and Week 16 to Week 52

PPS (Per-protocol set): all participants in the FAS (full analysis set) without any major protocol deviation.

Posted

Mean

Standard Deviation

Letters

from baseline to Week 52, baseline to Week 104, and Week 16 to Week 52

ID	Title	Description
OG000	Early-start T&E Arm	All participants during the initiation phase received Aflibercept (Eylea, BAY86-5321) 3 doses at Weeks 0, 4, and 8 followed by one dose 2Q8 (2 mg administered every 8 weeks) at Week 16. From Week 16 to Week 104 participants randomized to Early-start T&E arm (Treat and Extend arm) received treatment in individualized intervals of between 8 to16 weeks based on anatomical criteria.
OG001	Late-start T&E Arm	All participants during the initiation phase received Aflibercept (Eylea, BAY86-5321) 3 doses at Weeks 0, 4, and 8 followed by one dose 2Q8 (2 mg administered every 8 weeks) at Week 16. From Week 16 participants randomized to Late-start T&E arm received four 2Q8 injections. In Year 2 starting at Week 48, participants received treatment in individualized intervals of between 8 to16 weeks based on anatomical criteria.

Secondary

Percentage of Participants Maintaining Vision (<3 Lines Loss) at Week 52 Compared With Baseline

Participants maintained 3 lines (15 letters) vision loss in BCVA (Best-corrected visual acuity) as measured by the ETDRS (Early Treatment Diabetic Retinopathy Study) letter.

PPS (Per-protocol set): all participants in the FAS (full analysis set) without any major protocol deviation.

Posted

Number

Percentage

At week 52

ID	Title	Description
OG000	Early-start T&E Arm	All participants during the initiation phase received Aflibercept (Eylea, BAY86-5321) 3 doses at Weeks 0, 4, and 8 followed by one dose 2Q8 (2 mg administered every 8 weeks) at Week 16. From Week 16 to Week 104 participants randomized to Early-start T&E arm (Treat and Extend arm) received treatment in individualized intervals of between 8 to16 weeks based on anatomical criteria.
OG001	Late-start T&E Arm	All participants during the initiation phase received Aflibercept (Eylea, BAY86-5321) 3 doses at Weeks 0, 4, and 8 followed by one dose 2Q8 (2 mg administered every 8 weeks) at Week 16. From Week 16 participants randomized to Late-start T&E arm received four 2Q8 injections. In Year 2 starting at Week 48, participants received treatment in individualized intervals of between 8 to16 weeks based on anatomical criteria.

Secondary

Percentage of Participants Gained 3-line at Week 52 and Week 104 Compared With Baseline

Participants gained 3 lines (15 letters) in BCVA (Best-corrected visual acuity) as measured by the ETDRS (Early Treatment Diabetic Retinopathy Study) letter.

PPS (Per-protocol set): all participants in the FAS (full analysis set) without any major protocol deviation.

Posted

Number

Percentage

At Week 52 and Week 104

ID	Title	Description
OG000	Early-start T&E Arm	All participants during the initiation phase received Aflibercept (Eylea, BAY86-5321) 3 doses at Weeks 0, 4, and 8 followed by one dose 2Q8 (2 mg administered every 8 weeks) at Week 16. From Week 16 to Week 104 participants randomized to Early-start T&E arm (Treat and Extend arm) received treatment in individualized intervals of between 8 to16 weeks based on anatomical criteria.
OG001	Late-start T&E Arm	All participants during the initiation phase received Aflibercept (Eylea, BAY86-5321) 3 doses at Weeks 0, 4, and 8 followed by one dose 2Q8 (2 mg administered every 8 weeks) at Week 16. From Week 16 participants randomized to Late-start T&E arm received four 2Q8 injections. In Year 2 starting at Week 48, participants received treatment in individualized intervals of between 8 to16 weeks based on anatomical criteria.

Secondary

Change in Central Retinal Thickness (CRT)

CRT were evaluated using spectral domain Optical coherence tomograph (OCT).

PPS (Per-protocol set): all participants in the FAS (full analysis set) without any major protocol deviation.

Posted

Mean

Standard Deviation

μm

From baseline to Week 52, baseline to Week 104, Week 16 to Week 52, and Week 16 to Week 104

ID	Title	Description
OG000	Early-start T&E Arm	All participants during the initiation phase received Aflibercept (Eylea, BAY86-5321) 3 doses at Weeks 0, 4, and 8 followed by one dose 2Q8 (2 mg administered every 8 weeks) at Week 16. From Week 16 to Week 104 participants randomized to Early-start T&E arm (Treat and Extend arm) received treatment in individualized intervals of between 8 to16 weeks based on anatomical criteria.
OG001	Late-start T&E Arm	All participants during the initiation phase received Aflibercept (Eylea, BAY86-5321) 3 doses at Weeks 0, 4, and 8 followed by one dose 2Q8 (2 mg administered every 8 weeks) at Week 16. From Week 16 participants randomized to Late-start T&E arm received four 2Q8 injections. In Year 2 starting at Week 48, participants received treatment in individualized intervals of between 8 to16 weeks based on anatomical criteria.

Secondary

Number of Study Drug Injections From Baseline to Week 52 and Baseline to Week 104

PPS (Per-protocol set): all participants in the FAS (full analysis set) without any major protocol deviation.

Posted

Mean

Standard Deviation

injections

At Week 52 and Week 104

ID	Title	Description
OG000	Early-start T&E Arm	All participants during the initiation phase received Aflibercept (Eylea, BAY86-5321) 3 doses at Weeks 0, 4, and 8 followed by one dose 2Q8 (2 mg administered every 8 weeks) at Week 16. From Week 16 to Week 104 participants randomized to Early-start T&E arm (Treat and Extend arm) received treatment in individualized intervals of between 8 to16 weeks based on anatomical criteria.
OG001	Late-start T&E Arm	All participants during the initiation phase received Aflibercept (Eylea, BAY86-5321) 3 doses at Weeks 0, 4, and 8 followed by one dose 2Q8 (2 mg administered every 8 weeks) at Week 16. From Week 16 participants randomized to Late-start T&E arm received four 2Q8 injections. In Year 2 starting at Week 48, participants received treatment in individualized intervals of between 8 to16 weeks based on anatomical criteria.

Units	Counts
Participants

Secondary

Duration of Last Treatment Interval

PPS (Per-protocol set): all participants in the FAS (full analysis set) without any major protocol deviation.

Posted

Mean

Standard Deviation

Weeks

Early-Start T&E: from week 16 up to Week 104 or early termination; Late-Start T&E: From end of Year 1 up to Week 104 or early termination

ID	Title	Description
OG000	Early-start T&E Arm	All participants during the initiation phase received Aflibercept (Eylea, BAY86-5321) 3 doses at Weeks 0, 4, and 8 followed by one dose 2Q8 (2 mg administered every 8 weeks) at Week 16. From Week 16 to Week 104 participants randomized to Early-start T&E arm (Treat and Extend arm) received treatment in individualized intervals of between 8 to16 weeks based on anatomical criteria.
OG001	Late-start T&E Arm	All participants during the initiation phase received Aflibercept (Eylea, BAY86-5321) 3 doses at Weeks 0, 4, and 8 followed by one dose 2Q8 (2 mg administered every 8 weeks) at Week 16. From Week 16 participants randomized to Late-start T&E arm received four 2Q8 injections. In Year 2 starting at Week 48, participants received treatment in individualized intervals of between 8 to16 weeks based on anatomical criteria.

Units	Counts

Secondary

Percentage of Participants Requiring Retreatment at 8 Weeks, 10 Weeks, 12 Weeks, 14 Weeks, and 16 Weeks as the Last Treatment Interval

PPS (Per-protocol set): all participants in the FAS (full analysis set) without any major protocol deviation.

Posted

Number

percentage

at 8 weeks, 10 weeks, 12 weeks, 14 weeks, and 16 weeks

ID	Title	Description
OG000	Early-start T&E Arm	All participants during the initiation phase received Aflibercept (Eylea, BAY86-5321) 3 doses at Weeks 0, 4, and 8 followed by one dose 2Q8 (2 mg administered every 8 weeks) at Week 16. From Week 16 to Week 104 participants randomized to Early-start T&E arm (Treat and Extend arm) received treatment in individualized intervals of between 8 to16 weeks based on anatomical criteria.
OG001	Late-start T&E Arm	All participants during the initiation phase received Aflibercept (Eylea, BAY86-5321) 3 doses at Weeks 0, 4, and 8 followed by one dose 2Q8 (2 mg administered every 8 weeks) at Week 16. From Week 16 participants randomized to Late-start T&E arm received four 2Q8 injections. In Year 2 starting at Week 48, participants received treatment in individualized intervals of between 8 to16 weeks based on anatomical criteria.

Units	Counts

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Early-start T&E Arm	All participants during the initiation phase received Aflibercept (Eylea, BAY86-5321) 3 doses at Weeks 0, 4, and 8 followed by one dose 2Q8 (2 mg administered every 8 weeks) at Week 16. From Week 16 to Week 104 participants randomized to Early-start T&E arm (Treat and Extend arm) received treatment in individualized intervals of between 8 to16 weeks based on anatomical criteria.	3	135	29	135	93	135
EG001	Late-start T&E Arm	All participants during the initiation phase received Aflibercept (Eylea, BAY86-5321) 3 doses at Weeks 0, 4, and 8 followed by one dose 2Q8 (2 mg administered every 8 weeks) at Week 16. From Week 16 participants randomized to Late-start T&E arm received four 2Q8 injections. In Year 2 starting at Week 48, participants received treatment in individualized intervals of between 8 to16 weeks based on anatomical criteria.	4	136	35	136	80	136
EG002	Treated, But Not Randomized	Participants were treated during the initiation phase, received Aflibercept (Eylea, BAY86-5321) 3 doses at Weeks 0, 4 and 8 followed by one dose 2Q8 (2 mg administered every 8 weeks)at Week 16, but were not randomized to a treatment arm after the initiation phase.	0	16	3	16	10	16

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute myocardial infarction	Cardiac disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0021 events1 affected16 at risk
Atrial fibrillation	Cardiac disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Atrial flutter	Cardiac disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Atrioventricular block	Cardiac disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Atrioventricular block second degree	Cardiac disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Cardiac arrest	Cardiac disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA (22.0)	Non-systematic Assessment	EG0002 events2 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Cor pulmonale acute	Cardiac disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Coronary artery stenosis	Cardiac disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Myocardial infarction	Cardiac disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Pericardial haemorrhage	Cardiac disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Ventricular tachycardia	Cardiac disorders	MedDRA (22.0)	Non-systematic Assessment	EG0002 events1 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Congestive cardiomyopathy	Cardiac disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0012 events1 affected136 at risk EG0020 events0 affected16 at risk
Cardiac valve disease	Cardiac disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Eye inflammation	Eye disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Retinal artery embolism	Eye disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Visual acuity reduced	Eye disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0012 events2 affected136 at risk EG0020 events0 affected16 at risk
Visual impairment	Eye disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Eyelid cyst	Eye disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0002 events2 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Constipation	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0002 events1 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Duodenal ulcer perforation	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Gastritis	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Haematochezia	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Ileus	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0002 events2 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Intestinal perforation	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Large intestine polyp	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Noninfective sialoadenitis	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Hernia	General disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Pyrexia	General disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Multiple organ dysfunction syndrome	General disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Acute hepatic failure	Hepatobiliary disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Biliary colic	Hepatobiliary disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Cholangitis	Hepatobiliary disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA (22.0)	Non-systematic Assessment	EG0002 events2 affected135 at risk EG0012 events2 affected136 at risk EG0020 events0 affected16 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Bronchitis	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Cystitis	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Influenza	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0002 events2 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Pneumonia	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0004 events3 affected135 at risk EG0015 events5 affected136 at risk EG0020 events0 affected16 at risk
Pneumonia pseudomonal	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Sepsis	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Enterococcal sepsis	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Infective exacerbation of chronic obstructive airways disease	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0004 events3 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Adenovirus infection	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Concussion	Injury, poisoning and procedural complications	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Facial bones fracture	Injury, poisoning and procedural complications	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Splenic rupture	Injury, poisoning and procedural complications	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Traumatic fracture	Injury, poisoning and procedural complications	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Inflammation of wound	Injury, poisoning and procedural complications	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Pelvic fracture	Injury, poisoning and procedural complications	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Fluid overload	Metabolism and nutrition disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Intervertebral disc disorder	Musculoskeletal and connective tissue disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Fracture pain	Musculoskeletal and connective tissue disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Adenocarcinoma of colon	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Bladder neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Chronic myeloid leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Lung neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Epithelioid mesothelioma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Papillary renal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Carotid artery stenosis	Nervous system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Cerebral infarction	Nervous system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected136 at risk EG0022 events2 affected16 at risk
Haemorrhagic stroke	Nervous system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Hemiplegia	Nervous system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Vertebrobasilar insufficiency	Nervous system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Suicide attempt	Psychiatric disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
End stage renal disease	Renal and urinary disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0002 events1 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0013 events2 affected136 at risk EG0020 events0 affected16 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0012 events1 affected136 at risk EG0020 events0 affected16 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Implantable defibrillator replacement	Surgical and medical procedures	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Aortic aneurysm	Vascular disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Aortic dissection	Vascular disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Haematoma	Vascular disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Hypovolaemic shock	Vascular disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Intermittent claudication	Vascular disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Deep vein thrombosis	Vascular disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Extremity necrosis	Vascular disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Peripheral arterial occlusive disease	Vascular disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected136 at risk EG0020 events0 affected16 at risk
Peripheral artery stenosis	Vascular disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Blepharitis	Eye disorders	MedDRA (22.0)	Non-systematic Assessment	EG0006 events2 affected135 at risk EG00125 events11 affected136 at risk EG0020 events0 affected16 at risk
Cataract	Eye disorders	MedDRA (22.0)	Non-systematic Assessment	EG00014 events9 affected135 at risk EG00113 events8 affected136 at risk EG0020 events0 affected16 at risk
Cataract nuclear	Eye disorders	MedDRA (22.0)	Non-systematic Assessment	EG0004 events2 affected135 at risk EG00116 events7 affected136 at risk EG0020 events0 affected16 at risk
Conjunctival haemorrhage	Eye disorders	MedDRA (22.0)	Non-systematic Assessment	EG00026 events20 affected135 at risk EG00120 events18 affected136 at risk EG0020 events0 affected16 at risk
Corneal erosion	Eye disorders	MedDRA (22.0)	Non-systematic Assessment	EG0006 events5 affected135 at risk EG0013 events2 affected136 at risk EG0021 events1 affected16 at risk
Dry eye	Eye disorders	MedDRA (22.0)	Non-systematic Assessment	EG00011 events6 affected135 at risk EG00118 events11 affected136 at risk EG0020 events0 affected16 at risk
Erythema of eyelid	Eye disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0010 events0 affected136 at risk EG0022 events1 affected16 at risk
Macular degeneration	Eye disorders	MedDRA (22.0)	Non-systematic Assessment	EG0006 events6 affected135 at risk EG0015 events5 affected136 at risk EG0021 events1 affected16 at risk
Punctate keratitis	Eye disorders	MedDRA (22.0)	Non-systematic Assessment	EG00023 events10 affected135 at risk EG0019 events5 affected136 at risk EG0021 events1 affected16 at risk
Retinal haemorrhage	Eye disorders	MedDRA (22.0)	Non-systematic Assessment	EG0004 events4 affected135 at risk EG0017 events6 affected136 at risk EG0022 events2 affected16 at risk
Swelling of eyelid	Eye disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0010 events0 affected136 at risk EG0022 events1 affected16 at risk
Visual acuity reduced	Eye disorders	MedDRA (22.0)	Non-systematic Assessment	EG00024 events21 affected135 at risk EG00119 events17 affected136 at risk EG0021 events1 affected16 at risk
Visual impairment	Eye disorders	MedDRA (22.0)	Non-systematic Assessment	EG00011 events8 affected135 at risk EG0014 events4 affected136 at risk EG0020 events0 affected16 at risk
Vitreous floaters	Eye disorders	MedDRA (22.0)	Non-systematic Assessment	EG0008 events8 affected135 at risk EG0015 events4 affected136 at risk EG0020 events0 affected16 at risk
Vitreous adhesions	Eye disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0012 events2 affected136 at risk EG0021 events1 affected16 at risk
Choroidal neovascularisation	Eye disorders	MedDRA (22.0)	Non-systematic Assessment	EG0007 events7 affected135 at risk EG0015 events5 affected136 at risk EG0020 events0 affected16 at risk
Retinal pigment epithelial tear	Eye disorders	MedDRA (22.0)	Non-systematic Assessment	EG0003 events3 affected135 at risk EG0012 events2 affected136 at risk EG0021 events1 affected16 at risk
Neovascular age-related macular degeneration	Eye disorders	MedDRA (22.0)	Non-systematic Assessment	EG00015 events15 affected135 at risk EG00114 events14 affected136 at risk EG0021 events1 affected16 at risk
Macular fibrosis	Eye disorders	MedDRA (22.0)	Non-systematic Assessment	EG0002 events2 affected135 at risk EG0016 events6 affected136 at risk EG0021 events1 affected16 at risk
Gastroenteritis	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0013 events3 affected136 at risk EG0021 events1 affected16 at risk
Influenza	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG00012 events11 affected135 at risk EG00113 events12 affected136 at risk EG0020 events0 affected16 at risk
Nasopharyngitis	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG00021 events18 affected135 at risk EG00122 events17 affected136 at risk EG0020 events0 affected16 at risk
Foreign body in eye	Injury, poisoning and procedural complications	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0010 events0 affected136 at risk EG0021 events1 affected16 at risk
Post procedural swelling	Injury, poisoning and procedural complications	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0010 events0 affected136 at risk EG0021 events1 affected16 at risk
Dyslipidaemia	Metabolism and nutrition disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected135 at risk EG0010 events0 affected136 at risk EG0021 events1 affected16 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (22.0)	Non-systematic Assessment	EG0009 events8 affected135 at risk EG0011 events1 affected136 at risk EG0020 events0 affected16 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected135 at risk EG0012 events2 affected136 at risk EG0021 events1 affected16 at risk
Hypertension	Vascular disorders	MedDRA (22.0)	Non-systematic Assessment	EG00015 events13 affected135 at risk EG00111 events11 affected136 at risk EG0020 events0 affected16 at risk

ID	Term
D012162	Retinal Degeneration
D012164	Retinal Diseases
D005128	Eye Diseases