Study of Intravitreal REGN2176-3 in Participants With Neo... | NCT02418754

Status Module

Oversight Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
REGN2176-3 (1 mg: 2 mg)	Experimental	Intravitreal injection of REGN2176-3 (REGN2176 1 mg and REGN3 2 mg) every 4 weeks for 12 weeks. After Week 12, dosing was monthly up to Week 28, then criteria based re-dosing from Week 28-52.	Drug: REGN2176-3
REGN2176-3 (3 mg: 2 mg)	Experimental	Intravitreal injection of REGN2176-3 (REGN2176 3 mg and REGN3 2 mg) every 4 weeks for 12 weeks. After Week 12, dosing was monthly up to Week 28, then criteria based re-dosing from Week 28-52.	Drug: REGN2176-3
Intravitreal Aflibercept Injection (IAI) 2 mg	Experimental	IAI every 4 weeks for 12 weeks. After Week 12, dosing was monthly up to Week 28, then criteria based re-dosing from Week 28-52.	Drug: Intravitreal Aflibercept Injection (IAI)
REGN2176-3 (3 mg: 2 mg) to IAI 2 mg	Experimental	Intravitreal injection of REGN2176-3 (REGN2176 3 mg and REGN3 2 mg) every 4 weeks for 12 weeks. After Week 12, dosing was monthly with IAI 2 mg up to Week 28, then criteria based re-dosing from Week 28-52.	Drug: Intravitreal Aflibercept Injection (IAI)
IAI 2 mg to REGN2176-3 (3 mg:2 mg)	Experimental	IAI every 4 weeks for 12 weeks. After Week 12, dosing was monthly with REGN2176-3 (REGN2176 3 mg and REGN3 2 mg) up to Week 28, then criteria based re-dosing from Week 28-52.

Name	Type	Description	Arm Group Labels	Other Names
REGN2176-3	Drug		IAI 2 mg to REGN2176-3 (3 mg:2 mg) REGN2176-3 (1 mg: 2 mg) REGN2176-3 (3 mg: 2 mg)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Best Corrected Visual Acuity (BCVA) of the Study Eye at Week 12	Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol at 4 meters. BCVA score was measured using an eye chart and was reported as the number of letters read correctly at a testing distance of 4 meters using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. Change from baseline calculated by subtracting baseline value from observed post-baseline value at Week 12.	Baseline, Week 12

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Central Subfield Retinal Thickness (CST) at Week 12, as Measured by Optical Coherence Tomography (OCT)	CST was assessed using spectral domain optical coherence tomography (SD-OCT), a non-invasive diagnostic system providing high-resolution imaging sections of the retina. SD-OCT was performed in the study eye after pupil dilation. A negative change from baseline indicated improvement. Change from baseline calculated by subtracting baseline value from LOCF post-baseline value at Week 12.

Eligibility Module

Name	Affiliation	Role
Clinical Trial Management	Regeneron Pharmaceuticals	Study Director

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Group 1: REGN2176-3 (1 mg:2 mg)	Intravitreal injection of REGN2176-3 (REGN2176 1 mg and REGN3 2 mg) every 4 weeks for 12 weeks. At Week 12, Group 1 continued without a secondary randomization. After Week 12, dosing in Group 1 was monthly up to Week 28, then criteria based re-dosing from Week 28-52.
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Group 1: REGN2176-3 (1 mg:2 mg)	Intravitreal injection of REGN2176-3 (REGN2176 1 mg and REGN3 2 mg) every 4 weeks for 12 weeks. At Week 12, Group 1 continued without a secondary randomization. After Week 12, dosing in Group 1 was monthly up to Week 28, then criteria based re-dosing from Week 28-52.
BG001	Group 2: REGN2176-3 (3 mg:2 mg)	Intravitreal injection of REGN2176-3 (REGN2176 3 mg and REGN3 2 mg) every 4 weeks for 12 weeks. At Week 12, a secondary randomization occurred in Group 2 for those participants who completed the Week 12 assessments. After Week 12, dosing in Group 2 was monthly up to Week 28, then criteria based re-dosing from Week 28-52.
BG002	Group 3: Intravitreal Aflibercept Injection (IAI) 2 mg	IAI every 4 weeks for 12 weeks. At Week 12, a secondary randomization occurred in Group 3 for those participants who completed the Week 12 assessments. After Week 12, dosing in Group 3 was monthly up to Week 28, then criteria based re-dosing from Week 28-52.
BG003	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
	BG00079.2± 8.01 BG00178.6± 8.77 BG00277.7± 8.61 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00061 BG001121 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0001 BG0017 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Region of Enrollment

Number

Participants

Title

Denominators

Categories

United States

Title	Measurements
	BG00098 BG001193 BG002

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 Best Corrected Visual Acuity (BCVA) of the Study Eye at Week 12

Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol at 4 meters. BCVA score was measured using an eye chart and was reported as the number of letters read correctly at a testing distance of 4 meters using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. Change from baseline calculated by subtracting baseline value from observed post-baseline value at Week 12.

Full analysis set (FAS) that included all randomized participants who received any study treatment, had a baseline measurement of BCVA, and at least 1 post-baseline assessment of BCVA. Last observation carried forward (LOCF) method was used to impute missing data.

Posted

Least Squares Mean

Standard Error

Letters

Baseline, Week 12

ID	Title	Description
OG000	Group 1: REGN2176-3 (1 mg:2 mg)	Intravitreal injection of REGN2176-3 (REGN2176 1 mg and REGN3 2 mg) every 4 weeks for 12 weeks. At Week 12, Group 1 continued without a secondary randomization. After Week 12, dosing in Group 1 was monthly up to Week 28, then criteria based re-dosing from Week 28-52.
OG001	Group 2: REGN2176-3 (3 mg:2 mg)	Intravitreal injection of REGN2176-3 (REGN2176 3 mg and REGN3 2 mg) every 4 weeks for 12 weeks. At Week 12, a secondary randomization occurred in Group 2 for those participants who completed the Week 12 assessments. After Week 12, dosing in Group 2 was monthly up to Week 28, then criteria based re-dosing from Week 28-52.
OG002	Group 3: Intravitreal Aflibercept Injection (IAI) 2 mg	IAI every 4 weeks for 12 weeks. At Week 12, a secondary randomization occurred in Group 3 for those participants who completed the Week 12 assessments. After Week 12, dosing in Group 3 was monthly up to Week 28, then criteria based re-dosing from Week 28-52.

Units	Counts
Participants	OG000103 OG001200 OG002202

Title

Denominators

Categories

Title	Measurements
	OG0005.9± 1.01 OG0015.7± 0.73 OG0027.4± 0.72

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	To control for the family-wise type I error rate of 5%, for each of the 2 REGN2176-3 groups the 2-sided hypothesis comparing REGN2176-3 (1 mg: 2 mg) vs. Intravitreal Aflibercept Injection (IAI) 2 mg was tested at a significance level of α = 2.5%.	ANCOVA		0.2052	Threshold for significance at 0.025 level.	Least Squares (LS) Mean Difference	-1.58			2-Sided	95	-4.37	1.22					Superiority	Analysis was performed using analysis of covariance (ANCOVA) model with baseline measurements as covariate and treatment group, baseline angiographic choroidal neovascularization (CNV) subtype (predominantly or minimally classic versus occult versus occult with no classic lesions) as fixed factors.

Secondary

Change From Baseline in Central Subfield Retinal Thickness (CST) at Week 12, as Measured by Optical Coherence Tomography (OCT)

CST was assessed using spectral domain optical coherence tomography (SD-OCT), a non-invasive diagnostic system providing high-resolution imaging sections of the retina. SD-OCT was performed in the study eye after pupil dilation. A negative change from baseline indicated improvement. Change from baseline calculated by subtracting baseline value from LOCF post-baseline value at Week 12.

Analysis was performed on FAS. LOCF method was used to impute missing data.

Posted

Least Squares Mean

Standard Error

Microns

Baseline, Week 12

ID	Title	Description
OG000	Group 1: REGN2176-3 (1 mg:2 mg)	Intravitreal injection of REGN2176-3 (REGN2176 1 mg and REGN3 2 mg) every 4 weeks for 12 weeks. At Week 12, Group 1 continued without a secondary randomization. After Week 12, dosing in Group 1 was monthly up to Week 28, then criteria based re-dosing from Week 28-52.
OG001	Group 2: REGN2176-3 (3 mg:2 mg)	Intravitreal injection of REGN2176-3 (REGN2176 3 mg and REGN3 2 mg) every 4 weeks for 12 weeks. At Week 12, a secondary randomization occurred in Group 2 for those participants who completed the Week 12 assessments. After Week 12, dosing in Group 2 was monthly up to Week 28, then criteria based re-dosing from Week 28-52.

Secondary

Percentage of Participants With Complete Resolution of Intraretinal and Subretinal Fluid From Baseline at Week 12 Measured by Optical Coherence Tomography (OCT)

Analysis was performed on FAS. LOCF method was used to impute missing data.

Posted

Number

Percentage of Participants

Week 12

ID	Title	Description
OG000	Group 1: REGN2176-3 (1 mg:2 mg)	Intravitreal injection of REGN2176-3 (REGN2176 1 mg and REGN3 2 mg) every 4 weeks for 12 weeks. At Week 12, Group 1 continued without a secondary randomization. After Week 12, dosing in Group 1 was monthly up to Week 28, then criteria based re-dosing from Week 28-52.
OG001	Group 2: REGN2176-3 (3 mg:2 mg)	Intravitreal injection of REGN2176-3 (REGN2176 3 mg and REGN3 2 mg) every 4 weeks for 12 weeks. At Week 12, a secondary randomization occurred in Group 2 for those participants who completed the Week 12 assessments. After Week 12, dosing in Group 2 was monthly up to Week 28, then criteria based re-dosing from Week 28-52.
OG002	Group 3: Intravitreal Aflibercept Injection (IAI) 2 mg

Secondary

Change From Baseline in Choroidal Neovascularization (CNV) Area at Week 12 Measured by Fluorescein Angiography (FA)

The anatomical state of the retinal vasculature of the study eye and the fellow eye was evaluated by funduscopic examination, fundus photography and FA to evaluate the total lesion area, CNV area, classic CNV area, and fluorescein leakage. CNV area values measured in square millimeters, each disc area was equivalent to 2.54 mm^2 on the retina; lower values represent better outcomes.

Analysis was performed on FAS. LOCF was used to impute missing data. Here, number of participants analyzed = participants with available data for this outcome measure.

Posted

Least Squares Mean

Standard Error

Square Millimeter (mm^2)

Baseline, Week 12

ID	Title	Description
OG000	Group 1: REGN2176-3 (1 mg:2 mg)	Intravitreal injection of REGN2176-3 (REGN2176 1 mg and REGN3 2 mg) every 4 weeks for 12 weeks. At Week 12, Group 1 continued without a secondary randomization. After Week 12, dosing in Group 1 was monthly up to Week 28, then criteria based re-dosing from Week 28-52.
OG001	Group 2: REGN2176-3 (3 mg:2 mg)	Intravitreal injection of REGN2176-3 (REGN2176 3 mg and REGN3 2 mg) every 4 weeks for 12 weeks. At Week 12, a secondary randomization occurred in Group 2 for those participants who completed the Week 12 assessments. After Week 12, dosing in Group 2 was monthly up to Week 28, then criteria based re-dosing from Week 28-52.

Secondary

Change From Baseline in Total Lesion Size at Week 12 Measured by Fluorescein Angiography (FA)

Total Lesion Size was assessed by Fluorescein Angiography.

Analysis was performed on FAS. LOCF was used to impute missing data. Here, number of participants analyzed = participants with available data for this outcome measure.

Posted

Least Squares Mean

Standard Error

Baseline, Week 12

ID	Title	Description
OG000	Group 1: REGN2176-3 (1 mg:2 mg)	Intravitreal injection of REGN2176-3 (REGN2176 1 mg and REGN3 2 mg) every 4 weeks for 12 weeks. At Week 12, Group 1 continued without a secondary randomization. After Week 12, dosing in Group 1 was monthly up to Week 28, then criteria based re-dosing from Week 28-52.
OG001	Group 2: REGN2176-3 (3 mg:2 mg)	Intravitreal injection of REGN2176-3 (REGN2176 3 mg and REGN3 2 mg) every 4 weeks for 12 weeks. At Week 12, a secondary randomization occurred in Group 2 for those participants who completed the Week 12 assessments. After Week 12, dosing in Group 2 was monthly up to Week 28, then criteria based re-dosing from Week 28-52.
OG002	Group 3: Intravitreal Aflibercept Injection (IAI) 2 mg	IAI every 4 weeks for 12 weeks. At Week 12, a secondary randomization occurred in Group 3 for those participants who completed the Week 12 assessments. After Week 12, dosing in Group 3 was monthly up to Week 28, then criteria based re-dosing from Week 28-52.

Secondary

Percentage of Participants Who Gained At Least 15 Letters in BCVA From Baseline at Week 12, Measured by 4-meter Early Treatment Diabetic Retinopathy Scale (ETDRS)

Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol at 4 meters. BCVA score was measured using an eye chart and was reported as the number of letters read correctly at a testing distance of 4 meters using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. This outcome assessed the percentage of participants who gained 15 or more letters of visual acuity at Week 12 compared with baseline.

Analysis was performed on FAS. LOCF was used to impute missing data.

Posted

Number

Percentage of Participants

Week 12

ID	Title	Description
OG000	Group 1: REGN2176-3 (1 mg:2 mg)	Intravitreal injection of REGN2176-3 (REGN2176 1 mg and REGN3 2 mg) every 4 weeks for 12 weeks. At Week 12, Group 1 continued without a secondary randomization. After Week 12, dosing in Group 1 was monthly up to Week 28, then criteria based re-dosing from Week 28-52.
OG001	Group 2: REGN2176-3 (3 mg:2 mg)	Intravitreal injection of REGN2176-3 (REGN2176 3 mg and REGN3 2 mg) every 4 weeks for 12 weeks. At Week 12, a secondary randomization occurred in Group 2 for those participants who completed the Week 12 assessments. After Week 12, dosing in Group 2 was monthly up to Week 28, then criteria based re-dosing from Week 28-52.

Secondary

Percent Change From Baseline in Subretinal Hyperreflectivity Material (SHM) at Week 12 Measured by Optical Coherence Tomography (OCT)

SHM was assessed using spectral domain optical coherence tomography (SD-OCT), a non-invasive diagnostic system providing high-resolution imaging sections of the retina. SD-OCT was performed in the study eye after pupil dilation. A negative change from baseline indicated improvement.

Analysis was performed on FAS. LOCF was used to impute missing data. Here, number of participants analyzed = participants with available data for this outcome measure.

Posted

Least Squares Mean

Standard Error

Percent change

Baseline, Week 12

ID	Title	Description
OG000	Group 1: REGN2176-3 (1 mg:2 mg)	Intravitreal injection of REGN2176-3 (REGN2176 1 mg and REGN3 2 mg) every 4 weeks for 12 weeks. At Week 12, Group 1 continued without a secondary randomization. After Week 12, dosing in Group 1 was monthly up to Week 28, then criteria based re-dosing from Week 28-52.
OG001	Group 2: REGN2176-3 (3 mg:2 mg)	Intravitreal injection of REGN2176-3 (REGN2176 3 mg and REGN3 2 mg) every 4 weeks for 12 weeks. At Week 12, a secondary randomization occurred in Group 2 for those participants who completed the Week 12 assessments. After Week 12, dosing in Group 2 was monthly up to Week 28, then criteria based re-dosing from Week 28-52.

Secondary

Change From Baseline in Central Retinal/Lesion Thickness at Week 12 Measured by Optical Coherence Tomography (OCT)

Analysis was performed on FAS. LOCF was used to impute missing data.

Posted

Least Squares Mean

Standard Error

Microns

Baseline, Week 12

ID	Title	Description
OG000	Group 1: REGN2176-3 (1 mg:2 mg)	Intravitreal injection of REGN2176-3 (REGN2176 1 mg and REGN3 2 mg) every 4 weeks for 12 weeks. At Week 12, Group 1 continued without a secondary randomization. After Week 12, dosing in Group 1 was monthly up to Week 28, then criteria based re-dosing from Week 28-52.
OG001	Group 2: REGN2176-3 (3 mg:2 mg)	Intravitreal injection of REGN2176-3 (REGN2176 3 mg and REGN3 2 mg) every 4 weeks for 12 weeks. At Week 12, a secondary randomization occurred in Group 2 for those participants who completed the Week 12 assessments. After Week 12, dosing in Group 2 was monthly up to Week 28, then criteria based re-dosing from Week 28-52.
OG002

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	Group 1: REGN2176-3 (1 mg:2 mg)	Intravitreal injection of REGN2176-3 (REGN2176 1 mg and REGN3 2 mg) every 4 weeks for 12 weeks. At Week 12, Group 1 continued without a secondary randomization. After Week 12, dosing in Group 1 was monthly up to Week 28, then criteria based re-dosing from Week 28-52.	3	103	17	103	48	103
EG001	Group 2: REGN2176-3 (3 mg:2 mg)	Intravitreal injection of REGN2176-3 (REGN2176 3 mg and REGN3 2 mg) every 4 weeks for 12 weeks. At Week 12, a secondary randomization occurred in Group 2 for those participants who completed the Week 12 assessments. After Week 12, dosing in Group 2 was monthly up to Week 28, then criteria based re-dosing from Week 28-52.	2	106	20	106	50	106
EG002	Group 3: Intravitreal Aflibercept Injection (IAI) 2 mg	IAI every 4 weeks for 12 weeks. At Week 12, a secondary randomization occurred in Group 3 for those participants who completed the Week 12 assessments. After Week 12, dosing in Group 3 was monthly up to Week 28, then criteria based re-dosing from Week 28-52.	3	108	23	108	51	108
EG003	Group 4: REGN2176-3 (3 mg:2 mg) to IAI 2 mg	Intravitreal injection of REGN2176-3 (REGN2176 3 mg and REGN3 2 mg) every 4 weeks for 12 weeks. At Week 12, a secondary randomization occurred in Group 2 for those participants who completed the Week 12 assessments. After Week 12, dosing in Group 4 was monthly with IAI 2 mg up to Week 28, then criteria based re-dosing from Week 28-52.	1	94	17	94	52	94
EG004	Group 5: IAI 2 mg to REGN2176-3 (3 mg:2 mg)	IAI every 4 weeks for 12 weeks. At Week 12, a secondary randomization occurred in Group 3 for those participants who completed the Week 12 assessments. After Week 12, dosing in Group 5 was monthly with REGN2176-3 (REGN2176 3 mg and REGN3 2 mg) up to Week 28, then criteria based re-dosing from Week 28-52.	1	94	15	94	52	94

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment		EG0001 events1 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG0030 events0 affected94 at risk EG0041 events1 affected94 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA 18.0	Systematic Assessment		EG0001 events1 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Acute myocardial infarction	Cardiac disorders	MedDRA 18.0	Systematic Assessment		EG0001 events1 affected103 at risk EG0011 events1 affected106 at risk EG0020 events0 affected108 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 18.0	Systematic Assessment		EG0001 events1 affected103 at risk EG0011 events1 affected106 at risk EG0020 events0 affected108 at risk EG003
Bradycardia	Cardiac disorders	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0021 events1 affected108 at risk EG003
Cardiac failure congestive	Cardiac disorders	MedDRA 18.0	Systematic Assessment		EG0003 events3 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Cardio-Respiratory arrest	Cardiac disorders	MedDRA 18.0	Systematic Assessment		EG0001 events1 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Cardiomyopathy	Cardiac disorders	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Coronary artery disease	Cardiac disorders	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0021 events1 affected108 at risk EG003
Ischaemic cardiomyopathy	Cardiac disorders	MedDRA 18.0	Systematic Assessment		EG0001 events1 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Pericardial effusion	Cardiac disorders	MedDRA 18.0	Systematic Assessment		EG0001 events1 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Stress cardiomyopathy	Cardiac disorders	MedDRA 18.0	Systematic Assessment		EG0001 events1 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Blindness	Eye disorders	MedDRA 18.0	Systematic Assessment	Study eye	EG0001 events1 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Blindness transient	Eye disorders	MedDRA 18.0	Systematic Assessment	Study eye	EG0001 events1 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Macular degeneration	Eye disorders	MedDRA 18.0	Systematic Assessment	Study eye	EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0021 events1 affected108 at risk EG003
Neovascular age-related macular degeneration	Eye disorders	MedDRA 18.0	Systematic Assessment	Study eye	EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0021 events1 affected108 at risk EG003
Open angle glaucoma	Eye disorders	MedDRA 18.0	Systematic Assessment	Study eye	EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0021 events1 affected108 at risk EG003
Retinal haemorrhage	Eye disorders	MedDRA 18.0	Systematic Assessment	Study eye	EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Uveitis	Eye disorders	MedDRA 18.0	Systematic Assessment	Study eye	EG0002 events1 affected103 at risk EG0012 events2 affected106 at risk EG0020 events0 affected108 at risk EG003
Visual acuity reduced	Eye disorders	MedDRA 18.0	Systematic Assessment	Study eye	EG0002 events2 affected103 at risk EG0011 events1 affected106 at risk EG0020 events0 affected108 at risk EG003
Ileus	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0011 events1 affected106 at risk EG0020 events0 affected108 at risk EG003
Intestinal obstruction	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0011 events1 affected106 at risk EG0020 events0 affected108 at risk EG003
Large intestine polyp	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0021 events1 affected108 at risk EG003
Chest pain	General disorders	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0011 events1 affected106 at risk EG0020 events0 affected108 at risk EG003
Death	General disorders	MedDRA 18.0	Systematic Assessment		EG0001 events1 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Non-Cardiac chest pain	General disorders	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0011 events1 affected106 at risk EG0020 events0 affected108 at risk EG003
Hepatitis acute	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment		EG0001 events1 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Bronchitis	Infections and infestations	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0022 events2 affected108 at risk EG003
Device related infection	Infections and infestations	MedDRA 18.0	Systematic Assessment		EG0001 events1 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Diverticulitis	Infections and infestations	MedDRA 18.0	Systematic Assessment		EG0001 events1 affected103 at risk EG0011 events1 affected106 at risk EG0020 events0 affected108 at risk EG003
Endophthalmitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	Study eye	EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0021 events1 affected108 at risk EG003
Infectious colitis	Infections and infestations	MedDRA 18.0	Systematic Assessment		EG0001 events1 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Osteomyelitis	Infections and infestations	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0011 events1 affected106 at risk EG0020 events0 affected108 at risk EG003
Pneumonia	Infections and infestations	MedDRA 18.0	Systematic Assessment		EG0001 events1 affected103 at risk EG0011 events1 affected106 at risk EG0020 events0 affected108 at risk EG003
Sepsis	Infections and infestations	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0012 events2 affected106 at risk EG0020 events0 affected108 at risk EG003
Staphylococcal bacteraemia	Infections and infestations	MedDRA 18.0	Systematic Assessment		EG0002 events1 affected103 at risk EG0011 events1 affected106 at risk EG0020 events0 affected108 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0011 events1 affected106 at risk EG0020 events0 affected108 at risk EG003
Vestibular neuronitis	Infections and infestations	MedDRA 18.0	Systematic Assessment		EG0001 events1 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Ankle fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0021 events1 affected108 at risk EG003
Back injury	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment		EG0001 events1 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Comminuted fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0012 events2 affected106 at risk EG0021 events1 affected108 at risk EG003
Femur fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0012 events2 affected106 at risk EG0020 events0 affected108 at risk EG003
Humerus fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0021 events1 affected108 at risk EG003
Impacted fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0011 events1 affected106 at risk EG0020 events0 affected108 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Toxicity to various agents	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Blood pressure increased	Investigations	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0011 events1 affected106 at risk EG0020 events0 affected108 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0021 events1 affected108 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0021 events1 affected108 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Muscle haemorrhage	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0021 events1 affected108 at risk EG003
Bladder cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0021 events1 affected108 at risk EG003
Gastric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0022 events2 affected108 at risk EG003
Leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0011 events1 affected106 at risk EG0020 events0 affected108 at risk EG003
Lip squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0021 events1 affected108 at risk EG003
Lung adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0011 events1 affected106 at risk EG0020 events0 affected108 at risk EG003
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0011 events1 affected106 at risk EG0022 events2 affected108 at risk EG003
Non-Small cell lung cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0021 events1 affected108 at risk EG003
Oesophageal carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0021 events1 affected108 at risk EG003
Prostate cancer stage ii	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	Study eye	EG0001 events1 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment		EG0001 events1 affected103 at risk EG0010 events0 affected106 at risk EG0021 events1 affected108 at risk EG003
Basal ganglia stroke	Nervous system disorders	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0021 events1 affected108 at risk EG003
Carotid artery stenosis	Nervous system disorders	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Cerebrovascular accident	Nervous system disorders	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0011 events1 affected106 at risk EG0021 events1 affected108 at risk EG003
Dementia alzheimer's type	Nervous system disorders	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Dysarthria	Nervous system disorders	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Encephalopathy	Nervous system disorders	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0021 events1 affected108 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA 18.0	Systematic Assessment		EG0001 events1 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Metabolic encephalopathy	Nervous system disorders	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0021 events1 affected108 at risk EG003
Syncope	Nervous system disorders	MedDRA 18.0	Systematic Assessment		EG0001 events1 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Tremor	Nervous system disorders	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0021 events1 affected108 at risk EG003
Major depression	Psychiatric disorders	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Calculus ureteric	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0011 events1 affected106 at risk EG0020 events0 affected108 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0021 events1 affected108 at risk EG003
Nephrolithiasis	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0021 events1 affected108 at risk EG003
Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment		EG0002 events1 affected103 at risk EG0011 events1 affected106 at risk EG0020 events0 affected108 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0011 events1 affected106 at risk EG0020 events0 affected108 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment		EG0002 events1 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0021 events1 affected108 at risk EG003
Hypotension	Vascular disorders	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0011 events1 affected106 at risk EG0021 events1 affected108 at risk EG003
Peripheral ischaemia	Vascular disorders	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0011 events1 affected106 at risk EG0020 events0 affected108 at risk EG003
Shock haemorrhagic	Vascular disorders	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Neovascular age-related macular degeneration	Eye disorders	MedDRA 18.0	Systematic Assessment	Fellow eye	EG0001 events1 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment		EG0000 events0 affected103 at risk EG0010 events0 affected106 at risk EG0021 events1 affected108 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Cataract	Eye disorders	MedDRA 18.0	Systematic Assessment	Fellow eye	EG0006 events6 affected103 at risk EG0011 events1 affected106 at risk EG0022 events2 affected108 at risk EG0031 events1 affected94 at risk EG004
Conjunctival haemorrhage	Eye disorders	MedDRA 18.0	Systematic Assessment	Study eye	EG0006 events6 affected103 at risk EG0014 events4 affected106 at risk EG0027 events6 affected108 at risk EG003
Eye pain	Eye disorders	MedDRA 18.0	Systematic Assessment	Study eye	EG0003 events3 affected103 at risk EG0016 events5 affected106 at risk EG0021 events1 affected108 at risk EG003
Neovascular age-related macular degeneration	Eye disorders	MedDRA 18.0	Systematic Assessment	Fellow eye	EG0001 events1 affected103 at risk EG00110 events10 affected106 at risk EG0029 events8 affected108 at risk EG003
Posterior capsule opacification	Eye disorders	MedDRA 18.0	Systematic Assessment	Study eye	EG0001 events1 affected103 at risk EG0012 events2 affected106 at risk EG0021 events1 affected108 at risk EG003
Retinal haemorrhage	Eye disorders	MedDRA 18.0	Systematic Assessment	Study eye	EG0007 events6 affected103 at risk EG0018 events8 affected106 at risk EG0023 events3 affected108 at risk EG003
Vitreous detachment	Eye disorders	MedDRA 18.0	Systematic Assessment	Study eye	EG0003 events3 affected103 at risk EG0014 events3 affected106 at risk EG0022 events2 affected108 at risk EG003
Vitreous floaters	Eye disorders	MedDRA 18.0	Systematic Assessment	Study eye	EG0003 events2 affected103 at risk EG0011 events1 affected106 at risk EG0021 events1 affected108 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 18.0	Systematic Assessment		EG0003 events3 affected103 at risk EG0016 events6 affected106 at risk EG00212 events9 affected108 at risk EG003
Sinusitis	Infections and infestations	MedDRA 18.0	Systematic Assessment		EG0003 events2 affected103 at risk EG0018 events7 affected106 at risk EG0022 events2 affected108 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment		EG0008 events7 affected103 at risk EG0019 events7 affected106 at risk EG0024 events4 affected108 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment		EG0006 events5 affected103 at risk EG0016 events6 affected106 at risk EG0022 events2 affected108 at risk EG003
Hypertension	Vascular disorders	MedDRA 18.0	Systematic Assessment		EG0006 events6 affected103 at risk EG0014 events4 affected106 at risk EG00210 events10 affected108 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment		EG0003 events3 affected103 at risk EG0010 events0 affected106 at risk EG0022 events2 affected108 at risk EG003
Posterior capsule opacification	Eye disorders	MedDRA 18.0	Systematic Assessment	Fellow eye	EG0005 events5 affected103 at risk EG0011 events1 affected106 at risk EG0022 events2 affected108 at risk EG003
Vitreous floaters	Eye disorders	MedDRA 18.0	Systematic Assessment	Fellow eye	EG0002 events2 affected103 at risk EG0010 events0 affected106 at risk EG0020 events0 affected108 at risk EG003

Facility	Status	City	State	ZIP	Country	Contacts
		Phoenix	Arizona		United States