Study of the Efficacy and Safety of Intravitreal (IVT) Af... | NCT02718326

NCT02718326

ID	Type	Description	Link
2016-002639-14	EudraCT Number

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
Dosing regimen 1	Experimental	Participants will receive IVT aflibercept dosing regimen 1	Drug: Intravitreal aflibercept injection [IAI]
Dosing regimen 2	Experimental	Participants will receive IVT aflibercept dosing regimen 2	Drug: Intravitreal aflibercept injection [IAI]
Dosing regimen 3	Sham Comparator	Participants will receive matching sham injections	Drug: Sham

Name	Type	Description	Arm Group Labels	Other Names
Intravitreal aflibercept injection [IAI]	Drug		Dosing regimen 1 Dosing regimen 2	EYLEA® (aflibercept) Injection

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants Who Improved by ≥2 Steps From Baseline in the Diabetic Retinopathy Disease Severity Scale (DRSS) Score at Week 24 in the Combined 2Q16 and 2Q8 Groups	The Diabetic Retinopathy Disease Severity Scale (DRSS) may be used to describe overall retinopathy severity as well as the change in severity over time. Severity range from level 10 (DR absent) to level 85 (advanced proliferative DR: posterior fundus obscured, or center of macula detached). Here, DRSS describes severity level 47 (moderately severe NPDR) and level 53 (severe NPDR) at week 24 from baseline.	At Week 24
Percentage of Participants With a ≥ 2-step Change at Week 52 in Diabetic Retinopathy Severity Scale (DRSS) From Baseline	The Diabetic Retinopathy Disease Severity Scale (DRSS) may be used to describe overall retinopathy severity as well as the change in severity over time. Severity range from level 10 (DR absent) to level 85 (advanced proliferative DR: posterior fundus obscured, or center of macula detached). Here, DRSS describes severity level 47 (moderately severe NPDR) and level 53 (severe NPDR) at week 52 from baseline.	At Week 52

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants Who Developed a Vision-Threatening Complication Due to Diabetic Retinopathy at Week 52	Vision-threatening complications are defined as the composite outcome of proliferative diabetic retinopathy (PDR) (inclusive of participants who have vitreous hemorrhage or tractional retinal detachment believed to be due to PDR) and anterior segment neovascularization (ASNV) (participants with neovascularization of the iris [at least 2 cumulative clock hours], and/or definitive neovascularization of the iridocorneal angle).

Eligibility Module

Name	Affiliation	Role
Clinical Trial Management	Regeneron Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Regeneron Study Site		Phoenix	Arizona	85020	United States
Regeneron Study Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
34351414	Derived	Brown DM, Wykoff CC, Boyer D, Heier JS, Clark WL, Emanuelli A, Higgins PM, Singer M, Weinreich DM, Yancopoulos GD, Berliner AJ, Chu K, Reed K, Cheng Y, Vitti R. Evaluation of Intravitreal Aflibercept for the Treatment of Severe Nonproliferative Diabetic Retinopathy: Results From the PANORAMA Randomized Clinical Trial. JAMA Ophthalmol. 2021 Sep 1;139(9):946-955. doi: 10.1001/jamaophthalmol.2021.2809.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Sham Treatment	All participants received sham injections in the study eye every 4 weeks (Q4) to week 16 (after 5 initial monthly sham injections), followed by sham injections Q8 to week 96.
FG001	Intravitreal Aflibercept Injection (IAI) 2Q16

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	Jul 24, 2018	Aug 6, 2019

Arm/Group Information

ID	Title	Description
BG000	Sham Treatment	All participants received sham injections in the study eye every 4 weeks (Q4) to week 16 (after 5 initial monthly sham injections), followed by sham injections Q8 to week 96.
BG001	Intravitreal Aflibercept Injection (IAI) 2Q16	All participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96.
BG002	Intravitreal Aflibercept Injection (IAI) 2Q8	All participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.
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
	BG00055.8± 10.31 BG00155.4± 11.13 BG00255.8± 10.19 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00064 BG00160 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00074 BG00197 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0001 BG0011 BG002

Baseline Diabetic Retinopathy Severity Score (DRSS)

The Diabetic Retinopathy Disease Severity Scale (DRSS) may be used to describe overall retinopathy severity as well as the change in severity over time. Severity range from level 10 (DR absent) to level 85 (advanced proliferative DR: posterior fundus obscured, or center of macula detached).

Count of Participants

Participants

Title

Denominators

Categories

Level 47 (Moderately Severe)

Title	Measurements
	BG00099 BG001

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

Percentage of Participants Who Improved by ≥2 Steps From Baseline in the Diabetic Retinopathy Disease Severity Scale (DRSS) Score at Week 24 in the Combined 2Q16 and 2Q8 Groups

FAS included all randomized participants who received any study treatment as assigned at baseline (as randomized). The missing data were imputed using last observation carried forward (LOCF) method.

Posted

Number

Percentage of participants

At Week 24

ID	Title	Description
OG000	Sham Treatment	All participants received sham injections in the study eye every 4 weeks (Q4) to week 16 (after 5 initial monthly sham injections), followed by sham injections Q8 to week 96.
OG001	Intravitreal Aflibercept Injection (IAI) 2Q16	All participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96.
OG002	Intravitreal Aflibercept Injection (IAI) 2Q8	All participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.
OG003	IAI 2 mg Groups Combined (2Q16 & 2Q8)	IAI 2Q16: Participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96; IAI 2Q8: Participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.

Units	Counts
Participants	OG000133 OG001135 OG002134 OG003

Title

Denominators

Categories

Title	Measurements
	OG0006.0 OG00161.5 OG00255.2 OG003

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 OG003		Cochran-Mantel-Haenszel		<0.0001		percentage difference	52.3			2-Sided	95	45.2	59.5					Superiority

Primary

Percentage of Participants With a ≥ 2-step Change at Week 52 in Diabetic Retinopathy Severity Scale (DRSS) From Baseline

FAS included all randomized participants who received any study treatment as assigned at baseline (as randomized). The missing data were imputed using LOCF method.

Posted

Number

Percentage of participants

At Week 52

ID	Title	Description
OG000	Sham Treatment	All participants received sham injections in the study eye every 4 weeks (Q4) to week 16 (after 5 initial monthly sham injections), followed by sham injections Q8 to week 96.
OG001	Intravitreal Aflibercept Injection (IAI) 2Q16	All participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96.
OG002	Intravitreal Aflibercept Injection (IAI) 2Q8

Secondary

Percentage of Participants Who Developed a Vision-Threatening Complication Due to Diabetic Retinopathy at Week 52

Vision-threatening complications are defined as the composite outcome of proliferative diabetic retinopathy (PDR) (inclusive of participants who have vitreous hemorrhage or tractional retinal detachment believed to be due to PDR) and anterior segment neovascularization (ASNV) (participants with neovascularization of the iris [at least 2 cumulative clock hours], and/or definitive neovascularization of the iridocorneal angle).

FAS included all randomized participants who received any study treatment as assigned at baseline (as randomized).

Posted

Number

Percentage of participants

At Week 52

ID	Title	Description
OG000	Sham Treatment	All participants received sham injections in the study eye every 4 weeks (Q4) to week 16 (after 5 initial monthly sham injections), followed by sham injections Q8 to week 96.
OG001	Intravitreal Aflibercept Injection (IAI) 2Q16	All participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96.
OG002	Intravitreal Aflibercept Injection (IAI) 2Q8

Secondary

Percentage of Participants Who Developed Central Involved-Diabetic Macular Edema (CI-DME) at Week 52

The percentage of participants who developed CI-DME at week 52 were reported.

FAS included all randomized participants who received any study treatment as assigned at baseline (as randomized).

Posted

Number

Percentage of participants

At Week 52

ID	Title	Description
OG000	Sham Treatment	All participants received sham injections in the study eye every 4 weeks (Q4) to week 16 (after 5 initial monthly sham injections), followed by sham injections Q8 to week 96.
OG001	Intravitreal Aflibercept Injection (IAI) 2Q16	All participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96.
OG002	Intravitreal Aflibercept Injection (IAI) 2Q8	All participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.

Secondary

Time to Development of Any Neovascular Vision Threatening Complication (PDR/ASNV) Through Week 52

Vision-threatening complication (VTC) is defined as the composite outcome of proliferative diabetic retinopathy (PDR) (inclusive of participants who have vitreous hemorrhage or tractional retinal detachment believed to be due to PDR) and anterior segment neovascularization (ASNV) (participants with neovascularization of the iris [at least 2 cumulative clock hours], and/or definitive neovascularization of the iridocorneal angle). Vision Threatening Complications include PDR/ASNV identified by investigators and Diabetic Retinopathy Scale Score (DRSS) >61.

FAS included all randomized participants who received any study treatment as assigned at baseline (as randomized). Participants who did not have an event were censored at their last visit at or before the week 52 visit.

Here, the value "NA" = Not evaluable due to small number of VTC events.

Posted

Median

Inter-Quartile Range

Days

Baseline through week 52 (day 365)

ID	Title	Description
OG000	Sham Treatment	All participants received sham injections in the study eye every 4 weeks (Q4) to week 16 (after 5 initial monthly sham injections), followed by sham injections Q8 to week 96.
OG001	Intravitreal Aflibercept Injection (IAI) 2Q16	All participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96.

Secondary

Time to Development of Central Involved-Diabetic Macular Edema (CI-DME) Through Week 52

Time to develop Central Involved-Diabetic Macular Edema (CI-DME) through week 52 reported.

Posted

Median

Inter-Quartile Range

Days

Baseline through week 52 (day 365)

ID	Title	Description
OG000	Sham Treatment	All participants received sham injections in the study eye every 4 weeks (Q4) to week 16 (after 5 initial monthly sham injections), followed by sham injections Q8 to week 96.
OG001	Intravitreal Aflibercept Injection (IAI) 2Q16	All participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96.
OG002	Intravitreal Aflibercept Injection (IAI) 2Q8	All participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.

Secondary

Percentage of Participants Who Received Panretinal Photocoagulation (PRP), Inclusive of Participants Undergoing Vitrectomy With Endolaser, at Week 52

The percentage of participants who received panretinal photocoagulation (PRP), inclusive of participants undergoing vitrectomy with endolaser, at week 52 were reported.

FAS included all randomized participants who received any study treatment as assigned at baseline (as randomized).

Posted

Number

Percentage of participants

At Week 52

ID	Title	Description
OG000	Sham Treatment	All participants received sham injections in the study eye every 4 weeks (Q4) to week 16 (after 5 initial monthly sham injections), followed by sham injections Q8 to week 96.
OG001	Intravitreal Aflibercept Injection (IAI) 2Q16	All participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96.
OG002	Intravitreal Aflibercept Injection (IAI) 2Q8	All participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.

Secondary

Area Under the Curve (AUC) for Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 52

The area under the curve (AUC) is the area under the best corrected visual acuity (BCVA) versus time curve from baseline to week 52. Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. BCVA scale range is 0 (worst) to 100 (best).

AUC was calculated as a weighted average based on total AUC (using the trapezoidal rule) divided by total duration in days. FAS included all randomized participants who received any study treatment as assigned at baseline (as randomized).

Posted

Mean

Standard Deviation

scores on a scale

At week 52

ID	Title	Description
OG000	Sham Treatment	All participants received sham injections in the study eye every 4 weeks (Q4) to week 16 (after 5 initial monthly sham injections), followed by sham injections Q8 to week 96.
OG001	Intravitreal Aflibercept Injection (IAI) 2Q16	All participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96.
OG002	Intravitreal Aflibercept Injection (IAI) 2Q8

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	Sham Treatment	All participants received sham injections in the study eye every 4 weeks (Q4) to week 16 (after 5 initial monthly sham injections), followed by sham injections Q8 to week 96.	8	133	38	133	104	133
EG001	Intravitreal Aflibercept Injection (IAI) 2Q16	All participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96.	1	135	38	135	104	135
EG002	Intravitreal Aflibercept Injection (IAI) 2Q8	All participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.	3	134	47	134	106	134
EG003	IAI 2 mg Groups Combined (2Q16 & 2Q8)	IAI 2Q16: Participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96; IAI 2Q8: Participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.	4	269	85	269	210	269

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Coronary artery disease	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0015 events5 affected135 at risk EG0024 events4 affected134 at risk EG0039 events9 affected269 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0012 events2 affected135 at risk EG0023 events3 affected134 at risk EG003
Myocardial infarction	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0012 events2 affected135 at risk EG0021 events1 affected134 at risk EG003
Acute myocardial infarction	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0002 events2 affected133 at risk EG0012 events2 affected135 at risk EG0020 events0 affected134 at risk EG003
Cardiac failure acute	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0012 events1 affected135 at risk EG0021 events1 affected134 at risk EG003
Coronary artery stenosis	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0012 events2 affected135 at risk EG0020 events0 affected134 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Atrial flutter	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0011 events1 affected135 at risk EG0020 events0 affected134 at risk EG003
Cardiac arrest	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Cardiac failure chronic	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0011 events1 affected135 at risk EG0020 events0 affected134 at risk EG003
Myocardial ischaemia	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Supraventricular tachycardia	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0011 events1 affected135 at risk EG0020 events0 affected134 at risk EG003
Acute coronary syndrome	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0020 events0 affected134 at risk EG003
Cardiac failure	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0020 events0 affected134 at risk EG003
Ischaemic cardiomyopathy	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0020 events0 affected134 at risk EG003
Left ventricular dysfunction	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0020 events0 affected134 at risk EG003
Left ventricular failure	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0002 events2 affected133 at risk EG0010 events0 affected135 at risk EG0020 events0 affected134 at risk EG003
Pulseless electrical activity	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0020 events0 affected134 at risk EG003
Cellulitis	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0012 events2 affected135 at risk EG0026 events5 affected134 at risk EG003
Pneumonia	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0002 events2 affected133 at risk EG0013 events3 affected135 at risk EG0025 events3 affected134 at risk EG003
Diabetic foot infection	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0013 events3 affected135 at risk EG0020 events0 affected134 at risk EG003
Sepsis	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0023 events3 affected134 at risk EG003
Abscess limb	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0022 events2 affected134 at risk EG003
Arthritis bacterial	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Enterococcal bacteraemia	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Gastroenteritis viral	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Influenza	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Osteomyelitis	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0004 events4 affected133 at risk EG0011 events1 affected135 at risk EG0020 events0 affected134 at risk EG003
Osteomyelitis acute	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Pneumonia bacterial	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Sepsis syndrome	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0011 events1 affected135 at risk EG0020 events0 affected134 at risk EG003
Staphylococcal infection	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0011 events1 affected135 at risk EG0020 events0 affected134 at risk EG003
Staphylococcal osteomyelitis	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Staphylococcal skin infection	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0012 events1 affected135 at risk EG0020 events0 affected134 at risk EG003
Appendicitis	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0020 events0 affected134 at risk EG003
Diabetic gangrene	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0020 events0 affected134 at risk EG003
Infected skin ulcer	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0020 events0 affected134 at risk EG003
Septic shock	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0020 events0 affected134 at risk EG003
Anaemia postoperative	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Ankle fracture	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0011 events1 affected135 at risk EG0020 events0 affected134 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0011 events1 affected135 at risk EG0020 events0 affected134 at risk EG003
Femur fracture	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Fibula fracture	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Meniscus injury	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0011 events1 affected135 at risk EG0020 events0 affected134 at risk EG003
Postoperative respiratory failure	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Postoperative thoracic procedure complication	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0011 events1 affected135 at risk EG0020 events0 affected134 at risk EG003
Radius fracture	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Skin laceration	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Tibia fracture	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Traumatic arthropathy	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0011 events1 affected135 at risk EG0020 events0 affected134 at risk EG003
Ulna fracture	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Limb injury	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0020 events0 affected134 at risk EG003
Pneumocephalus	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0020 events0 affected134 at risk EG003
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0020 events0 affected134 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0023 events3 affected134 at risk EG003
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0012 events2 affected135 at risk EG0020 events0 affected134 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0012 events2 affected135 at risk EG0020 events0 affected134 at risk EG003
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Gout	Metabolism and nutrition disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0011 events1 affected135 at risk EG0020 events0 affected134 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0020 events0 affected134 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0020 events0 affected134 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA (22.0)	Systematic Assessment	EG0002 events2 affected133 at risk EG0011 events1 affected135 at risk EG0023 events3 affected134 at risk EG003
Chronic kidney disease	Renal and urinary disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0011 events1 affected135 at risk EG0020 events0 affected134 at risk EG003
End stage renal disease	Renal and urinary disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Urge incontinence	Renal and urinary disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0011 events1 affected135 at risk EG0020 events0 affected134 at risk EG003
Urinary retention	Renal and urinary disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0011 events1 affected135 at risk EG0020 events0 affected134 at risk EG003
Cerebrovascular accident	Nervous system disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0013 events3 affected135 at risk EG0021 events1 affected134 at risk EG003
Brain stem stroke	Nervous system disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0011 events1 affected135 at risk EG0020 events0 affected134 at risk EG003
Cerebral infarction	Nervous system disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0011 events1 affected135 at risk EG0020 events0 affected134 at risk EG003
Hepatic encephalopathy	Nervous system disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Hypoglycaemic unconsciousness	Nervous system disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0020 events0 affected134 at risk EG003
Ischaemic stroke	Nervous system disorders	MedDRA (22.0)	Systematic Assessment	EG0003 events3 affected133 at risk EG0010 events0 affected135 at risk EG0020 events0 affected134 at risk EG003
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0022 events2 affected134 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Systematic Assessment	EG0002 events2 affected133 at risk EG0011 events1 affected135 at risk EG0021 events1 affected134 at risk EG003
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Pulmonary arterial hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Respiratory acidosis	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0011 events1 affected135 at risk EG0020 events0 affected134 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0011 events1 affected135 at risk EG0020 events0 affected134 at risk EG003
Pulmonary congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0020 events0 affected134 at risk EG003
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Systematic Assessment	EG0002 events2 affected133 at risk EG0010 events0 affected135 at risk EG0020 events0 affected134 at risk EG003
Cervix carcinoma stage 0	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Gastric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0011 events1 affected135 at risk EG0020 events0 affected134 at risk EG003
Malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Pancreatic carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Transitional cell carcinoma metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0020 events0 affected134 at risk EG003
Papillary thyroid cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Systematic Assessment	EG0002 events1 affected133 at risk EG0010 events0 affected135 at risk EG0020 events0 affected134 at risk EG003
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0020 events0 affected134 at risk EG003
Diabetic gastroparesis	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Faecaloma	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Impaired gastric emptying	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0025 events1 affected134 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0011 events1 affected135 at risk EG0020 events0 affected134 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0020 events0 affected134 at risk EG003
Ileus	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0020 events0 affected134 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0020 events0 affected134 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Cholecystitis chronic	Hepatobiliary disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Diabetic foot	Skin and subcutaneous tissue disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0011 events1 affected135 at risk EG0022 events2 affected134 at risk EG003
Photosensitivity reaction	Skin and subcutaneous tissue disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0020 events0 affected134 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0012 events2 affected135 at risk EG0020 events0 affected134 at risk EG003
Chest pain	General disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0011 events1 affected135 at risk EG0020 events0 affected134 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Asthenia	General disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0020 events0 affected134 at risk EG003
Generalised oedema	General disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0020 events0 affected134 at risk EG003
Pyrexia	General disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0020 events0 affected134 at risk EG003
Blood glucose increased	Investigations	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Blood sodium decreased	Investigations	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Bipolar disorder	Psychiatric disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0011 events1 affected135 at risk EG0020 events0 affected134 at risk EG003
Peripheral ischaemia	Vascular disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Arteriosclerosis	Vascular disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0020 events0 affected134 at risk EG003
Hypotension	Vascular disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0020 events0 affected134 at risk EG003
Visual acuity reduced Fellow Eye	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0023 events3 affected134 at risk EG003
Diabetic retinal oedema Fellow Eye	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Macular fibrosis Fellow Eye	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Macular hole Fellow Eye	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Retinal vein occlusion Fellow Eye	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0011 events1 affected135 at risk EG0020 events0 affected134 at risk EG003
Visual impairment Fellow Eye	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Vitreous adhesions Fellow Eye	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Vitreous haemorrhage Fellow Eye	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0011 events1 affected135 at risk EG0020 events0 affected134 at risk EG003
Cataract Fellow Eye	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0020 events0 affected134 at risk EG003
Iris neovascularisation Fellow Eye	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG0002 events2 affected133 at risk EG0010 events0 affected135 at risk EG0020 events0 affected134 at risk EG003
Cystoid macular oedema Study Eye	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0022 events1 affected134 at risk EG003
Visual acuity reduced Study Eye	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Vitreous haemorrhage Study Eye	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003
Diabetic retinopathy Study Eye	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG0002 events1 affected133 at risk EG0010 events0 affected135 at risk EG0020 events0 affected134 at risk EG003
Iris neovascularisation Study Eye	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0020 events0 affected134 at risk EG003
Retinal neovascularisation Study Eye	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected135 at risk EG0020 events0 affected134 at risk EG003
Traumatic fracture Study Eye	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected135 at risk EG0021 events1 affected134 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Constipation	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG0003 events3 affected133 at risk EG0015 events5 affected135 at risk EG0027 events7 affected134 at risk EG00312 events12 affected269 at risk
Nausea	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG0009 events8 affected133 at risk EG0015 events5 affected135 at risk EG00214 events6 affected134 at risk EG003
Bronchitis	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0007 events7 affected133 at risk EG00110 events9 affected135 at risk EG0025 events5 affected134 at risk EG003
Cellulitis	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0006 events6 affected133 at risk EG00110 events5 affected135 at risk EG0027 events7 affected134 at risk EG003
Influenza	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0008 events8 affected133 at risk EG00112 events10 affected135 at risk EG0024 events4 affected134 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG00016 events15 affected133 at risk EG00116 events11 affected135 at risk EG00212 events11 affected134 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG00022 events16 affected133 at risk EG00113 events12 affected135 at risk EG00213 events11 affected134 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0005 events5 affected133 at risk EG0017 events5 affected135 at risk EG00211 events8 affected134 at risk EG003
Blood glucose increased	Investigations	MedDRA (22.0)	Systematic Assessment	EG0008 events7 affected133 at risk EG0013 events3 affected135 at risk EG0027 events7 affected134 at risk EG003
Glycosylated haemoglobin increased	Investigations	MedDRA (22.0)	Systematic Assessment	EG0007 events7 affected133 at risk EG0019 events9 affected135 at risk EG0029 events9 affected134 at risk EG003
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA (22.0)	Systematic Assessment	EG00015 events13 affected133 at risk EG00111 events11 affected135 at risk EG0028 events8 affected134 at risk EG003
Headache	Nervous system disorders	MedDRA (22.0)	Systematic Assessment	EG0002 events2 affected133 at risk EG0019 events7 affected135 at risk EG0028 events8 affected134 at risk EG003
Hypertension	Vascular disorders	MedDRA (22.0)	Systematic Assessment	EG00028 events25 affected133 at risk EG00132 events28 affected135 at risk EG00223 events20 affected134 at risk EG003
Blepharitis Fellow Eye	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0013 events3 affected135 at risk EG0027 events7 affected134 at risk EG003
Cataract Fellow Eye	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG0004 events4 affected133 at risk EG0019 events9 affected135 at risk EG0024 events4 affected134 at risk EG003
Conjunctival haemorrhage Fellow Eye	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG0007 events6 affected133 at risk EG00114 events5 affected135 at risk EG00214 events8 affected134 at risk EG003
Diabetic retinal oedema Fellow Eye	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG00025 events19 affected133 at risk EG00124 events17 affected135 at risk EG00227 events23 affected134 at risk EG003
Diabetic retinopathy Fellow Eye	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG00013 events12 affected133 at risk EG00114 events13 affected135 at risk EG00210 events10 affected134 at risk EG003
Macular oedema Fellow Eye	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG0004 events4 affected133 at risk EG0017 events7 affected135 at risk EG0026 events6 affected134 at risk EG003
Retinal exudates Fellow Eye	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG0009 events8 affected133 at risk EG0012 events2 affected135 at risk EG0027 events6 affected134 at risk EG003
Vitreous haemorrhage Fellow Eye	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG0004 events4 affected133 at risk EG00112 events8 affected135 at risk EG0023 events3 affected134 at risk EG003
Blepharitis Study Eye	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected133 at risk EG0012 events2 affected135 at risk EG0027 events7 affected134 at risk EG003
Cataract Study Eye	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG0005 events5 affected133 at risk EG0018 events8 affected135 at risk EG0028 events8 affected134 at risk EG003
Conjunctival haemorrhage Study Eye	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG00014 events8 affected133 at risk EG00127 events18 affected135 at risk EG00234 events25 affected134 at risk EG003
Diabetic retinal oedema Study Eye	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG00054 events43 affected133 at risk EG00122 events14 affected135 at risk EG00225 events19 affected134 at risk EG003
Diabetic retinopathy Study Eye	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG00025 events22 affected133 at risk EG0014 events3 affected135 at risk EG0025 events5 affected134 at risk EG003
Eye pain Study Eye	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG0008 events6 affected133 at risk EG00113 events11 affected135 at risk EG0025 events5 affected134 at risk EG003
Retinal exudates Study Eye	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG0007 events6 affected133 at risk EG0015 events5 affected135 at risk EG0029 events9 affected134 at risk EG003
Vitreous detachment Study Eye	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG0004 events4 affected133 at risk EG0017 events7 affected135 at risk EG0029 events7 affected134 at risk EG003
Vitreous floaters Study Eye	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG0003 events3 affected133 at risk EG0018 events7 affected135 at risk EG00213 events13 affected134 at risk EG003

ID	Term
C533178	aflibercept
D007267	Injections
C005703	salicylhydroxamic acid

ID	Term
D004333	Drug Administration Routes
D004358	Drug Therapy
D013812	Therapeutics