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Trial record 12 of 124 for:    regeneron AND VEGF Trap-Eye

Study of Intravitreal Aflibercept Injection (IAI; EYLEA®; BAY86-5321) in Patients With Diabetic Macular Edema (VISTA DME)

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ClinicalTrials.gov Identifier: NCT01363440
Recruitment Status : Completed
First Posted : June 1, 2011
Results First Posted : April 20, 2015
Last Update Posted : May 30, 2016
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Diabetic Macular Edema
Interventions Drug: Intravitreal Aflibercept Injection (IAI; EYLEA®; BAY86-5321)
Procedure: Macular Laser Photocoagulation
Enrollment 466

Recruitment Details Participants with diabetic macular edema (DME) secondary to diabetes mellitus involving the center of the macula in the study eye could participate in the study.
Pre-assignment Details Of 687 participants who were screened for inclusion in the study, 466 were enrolled (started) and 461 received treatment.
Arm/Group Title Macular Laser Photocoagulation Treatment (Control) Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q4 Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q8
Hide Arm/Group Description Participants received macular laser treatment at baseline and as-needed at visits at which laser re-treatment criteria were met, but no more frequently than every 12 weeks. Participants received 2mg Intravitreal aflibercept injection (IAI) every 4 weeks. Participants received 2mg Intravitreal aflibercept injection (IAI) every 4 weeks for 5 visits followed by injections every 8 weeks.
Period Title: Overall Study
Started 156 [1] 156 [1] 154 [1]
Participants Received Treatment 154 [2] 155 [2] 152 [2]
Completed Week 52 145 146 144
Completed Week 100 133 125 127
Completed 133 [3] 125 [3] 127 [3]
Not Completed 23 31 27
Reason Not Completed
Adverse Event             5             4             4
Death             3             7             5
Withdrawal by Subject             9             11             11
Lost to Follow-up             2             4             5
Other             4             5             2
[1]
randomized
[2]
safety analysis set (SAF)
[3]
Completed Week 100
Arm/Group Title Control Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q4 Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q8 Total
Hide Arm/Group Description Participants received macular laser treatment at baseline and as-needed at visits at which laser re-treatment criteria were met, but no more frequently than every 12 weeks. Participants received 2mg Intravitreal aflibercept injection (IAI) every 4 weeks. Participants received 2mg Intravitreal aflibercept injection (IAI) every 4 weeks for 5 visits followed by injections every 8 weeks. Total of all reporting groups
Overall Number of Baseline Participants 154 155 152 461
Hide Baseline Analysis Population Description
Baseline population analyzed using the SAF
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 154 participants 155 participants 152 participants 461 participants
61.7  (8.65) 62  (11.16) 63.1  (9.36) 62.2  (9.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 154 participants 155 participants 152 participants 461 participants
Female
69
  44.8%
68
  43.9%
73
  48.0%
210
  45.6%
Male
85
  55.2%
87
  56.1%
79
  52.0%
251
  54.4%
1.Primary Outcome
Title Change From Baseline in Best Corrected Visual Acuity (BCVA) as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 52 - Last Observation Carried Forward (LOCF)
Hide Description Visual function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score of 73 to 24 (= Acuity of 20/40 to 20/320) in the study eye were included; a higher score represents better functioning.
Time Frame Baseline and Week 52
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Primary efficacy endpoint was analyzed using the full analysis set (FAS). The FAS included all 'Participants received Treatment' and had a baseline and at least 1 post-baseline assessment of Best Corrected Visual Acuity (BCVA).
Arm/Group Title Control Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q4 Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q8
Hide Arm/Group Description:
Participants received macular laser treatment at baseline and as-needed at visits at which laser re-treatment criteria were met, but no more frequently than every 12 weeks.
Participants received 2mg Intravitreal aflibercept injection (IAI) every 4 weeks.
Participants received 2mg Intravitreal aflibercept injection (IAI) every 4 weeks for 5 visits followed by injections every 8 weeks.
Overall Number of Participants Analyzed 154 154 151
Least Squares Mean (Standard Error)
Unit of Measure: letters correctly read
.10  (1.03) 12.3  (.76) 10.6  (.69)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Control, Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q4
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 12.19
Confidence Interval (2-Sided) 97.5%
9.35 to 15.04
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Control, Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q8
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 10.45
Confidence Interval (2-Sided) 97.5%
7.73 to 13.17
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants Who Gained at Least 10 Letters in BCVA as Measured by ETDRS Letter Score Compared With Baseline at Week 52 - LOCF
Hide Description [Not Specified]
Time Frame Baseline and Week 52
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All secondary efficacy endpoints were analyzed using the full analysis set (FAS). The FAS included all 'Participants received Treatment' and had a baseline and at least 1 post-baseline assessment of Best Corrected Visual Acuity (BCVA).
Arm/Group Title Control Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q4 Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q8
Hide Arm/Group Description:
Participants received macular laser treatment at baseline and as-needed at visits at which laser re-treatment criteria were met, but no more frequently than every 12 weeks.
Participants received 2mg Intravitreal aflibercept injection (IAI) every 4 weeks.
Participants received 2mg Intravitreal aflibercept injection (IAI) every 4 weeks for 5 visits followed by injections every 8 weeks.
Overall Number of Participants Analyzed 154 154 151
Measure Type: Number
Unit of Measure: percentage of participants
30 100 88
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Control, Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q4
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 45.9
Confidence Interval (2-Sided) 97.5%
34.7 to 57.0
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Control, Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q8
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 38.8
Confidence Interval (2-Sided) 97.5%
27.2 to 50.3
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants Who Gained at Least 15 Letters in BCVA as Measured by ETDRS Letter Score Compared With Baseline at Week 52 - LOCF
Hide Description [Not Specified]
Time Frame Baseline and Week 52
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Control Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q4 Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q8
Hide Arm/Group Description:
Participants received macular laser treatment at baseline and as-needed at visits at which laser re-treatment criteria were met, but no more frequently than every 12 weeks.
Participants received 2mg Intravitreal aflibercept injection (IAI) every 4 weeks.
Participants received 2mg Intravitreal aflibercept injection (IAI) every 4 weeks for 5 visits followed by injections every 8 weeks.
Overall Number of Participants Analyzed 154 154 151
Measure Type: Number
Unit of Measure: percentage of participants
12 64 47
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Control, Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q4
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 34.2
Confidence Interval (2-Sided) 97.5%
24.1 to 44.4
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Control, Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q8
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 23.3
Confidence Interval (2-Sided) 97.5%
13.5 to 33.1
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants With a ≥2-step Improvement From Baseline in the ETDRS DRSS (Diabetic Retinopathy Severity Score) as Assessed by FP (Fundus Photography) at Week 52 - LOCF
Hide Description Baseline ETDRS DRSS: None (level 10); Mild to moderate nonproliferative DR (levels 14, 15, 20, 35, and 43); Moderately severe/severe nonproliferative DR (levels 47 and 53); Mild/moderate/high-risk/advanced proliferative DR (levels 61, 65, 71,75, 81, and 85)
Time Frame Baseline and Week 52
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Control Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q4 Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q8
Hide Arm/Group Description:
Participants received macular laser treatment at baseline and as-needed at visits at which laser re-treatment criteria were met, but no more frequently than every 12 weeks.
Participants received 2mg Intravitreal aflibercept injection (IAI) every 4 weeks.
Participants received 2mg Intravitreal aflibercept injection (IAI) every 4 weeks for 5 visits followed by injections every 8 weeks.
Overall Number of Participants Analyzed 154 154 151
Measure Type: Number
Unit of Measure: percentage of participants
22 52 44
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Control, Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q4
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 19.7
Confidence Interval (2-Sided) 97.5%
9.0 to 30.4
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Control, Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q8
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0017
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 14.9
Confidence Interval (2-Sided) 97.5%
4.4 to 25.4
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Central Retinal Thickness (CRT) at Week 52 as Assessed on Optical Coherence Tomography (OCT) - LOCF
Hide Description [Not Specified]
Time Frame Baseline and Week 52
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Control Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q4 Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q8
Hide Arm/Group Description:
Participants received macular laser treatment at baseline and as-needed at visits at which laser re-treatment criteria were met, but no more frequently than every 12 weeks.
Participants received 2mg Intravitreal aflibercept injection (IAI) every 4 weeks.
Participants received 2mg Intravitreal aflibercept injection (IAI) every 4 weeks for 5 visits followed by injections every 8 weeks.
Overall Number of Participants Analyzed 154 154 151
Least Squares Mean (Standard Error)
Unit of Measure: microns
-73.3  (12.09) -184.1  (6.57) -186.8  (6.90)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Control, Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q4
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -110.8
Confidence Interval (2-Sided) 97.5%
-141.3 to -80.22
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Control, Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q8
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -113.5
Confidence Interval (2-Sided) 97.5%
-144.2 to -82.75
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Near Activities Subscale at Week 52 - LOCF
Hide Description The NEI VFQ-25 total score ranges from 0-100 with a score of 0 being the worst outcome and 100 being the best outcome. The NEI VFQ questionnaire is organized as a collection of subscales that are all scored from 0-100. Near activities are defined as reading ordinary print in newspapers, performing work or hobbies requiring near vision, or finding something on a crowded shelf.
Time Frame Baseline and Week 52
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Control Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q4 Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q8
Hide Arm/Group Description:
Participants received macular laser treatment at baseline and as-needed at visits at which laser re-treatment criteria were met, but no more frequently than every 12 weeks.
Participants received 2mg Intravitreal aflibercept injection (IAI) every 4 weeks.
Participants received 2mg Intravitreal aflibercept injection (IAI) every 4 weeks for 5 visits followed by injections every 8 weeks.
Overall Number of Participants Analyzed 154 154 151
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
3.7  (1.55) 8.9  (1.58) 8.1  (1.44)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Control, Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q4
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0168
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 5.19
Confidence Interval 97.5%
0.33 to 10.04
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Control, Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q8
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0323
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 4.36
Confidence Interval (2-Sided) 97.5%
-0.21 to 8.93
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Distance Activities Subscale at Week 52 - LOCF
Hide Description The NEI VFQ-25 total score ranges from 0-100 with a score of 0 being the worst outcome and 100 being the best outcome. The NEI VFQ questionnaire is organized as a collection of subscales that are all scored from 0-100. Distance activities are defined as reading street signs or names on stores, and going down stairs, steps, or curbs.
Time Frame Baseline and Week 52
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Control Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q4 Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q8
Hide Arm/Group Description:
Participants received macular laser treatment at baseline and as-needed at visits at which laser re-treatment criteria were met, but no more frequently than every 12 weeks.
Participants received 2mg Intravitreal aflibercept injection (IAI) every 4 weeks.
Participants received 2mg Intravitreal aflibercept injection (IAI) every 4 weeks for 5 visits followed by injections every 8 weeks.
Overall Number of Participants Analyzed 154 154 151
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
4.9  (1.44) 7.7  (1.57) 6.5  (1.48)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Control, Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q4
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1702
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.86
Confidence Interval (2-Sided) 97.5%
-1.82 to 7.54
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Control, Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q8
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4067
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.65
Confidence Interval (2-Sided) 97.5%
-2.83 to 6.13
Estimation Comments [Not Specified]
Time Frame From the first study drug injection until 30 days after the last study drug injection at the latest from week 0 to week 100; From the first study drug injection until 30 days after the last study drug injection at the latest from week 0 to week 148.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Control (Week 0 to Week 100) IAI;EYLEA®;BAY86-5321 2Q4 (Week 0 to Week 100) IAI;EYLEA®;BAY86-5321) 2Q8 (Week 0 to Week 100) Control (Week 0 to Week 148) IAI;EYLEA®;BAY86-5321 2Q4 (Week 0 to Week 148) IAI;EYLEA®;BAY86-5321) 2Q8 (Week 0 to Week 148)
Hide Arm/Group Description Participants received macular laser treatment at baseline and as-needed at visits at which laser re-treatment criteria were met, but no more frequently than every 12 weeks. Participants received 2mg Intravitreal aflibercept injection (IAI) every 4 weeks. Participants received 2mg Intravitreal aflibercept injection (IAI) every 4 weeks for 5 visits followed by injections every 8 weeks. Participants received macular laser treatment at baseline and as-needed at visits at which laser re-treatment criteria were met, but no more frequently than every 12 weeks. Participants received 2mg Intravitreal aflibercept injection(IAI) every 4 weeks. Participants received 2mg Intravitreal aflibercept injection (IAI) every 4 weeks for 5 visits followed by injections every 8 weeks.
All-Cause Mortality
Control (Week 0 to Week 100) IAI;EYLEA®;BAY86-5321 2Q4 (Week 0 to Week 100) IAI;EYLEA®;BAY86-5321) 2Q8 (Week 0 to Week 100) Control (Week 0 to Week 148) IAI;EYLEA®;BAY86-5321 2Q4 (Week 0 to Week 148) IAI;EYLEA®;BAY86-5321) 2Q8 (Week 0 to Week 148)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Control (Week 0 to Week 100) IAI;EYLEA®;BAY86-5321 2Q4 (Week 0 to Week 100) IAI;EYLEA®;BAY86-5321) 2Q8 (Week 0 to Week 100) Control (Week 0 to Week 148) IAI;EYLEA®;BAY86-5321 2Q4 (Week 0 to Week 148) IAI;EYLEA®;BAY86-5321) 2Q8 (Week 0 to Week 148)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   67/154 (43.51%)   67/155 (43.23%)   56/152 (36.84%)   84/154 (54.55%)   85/155 (54.84%)   75/152 (49.34%) 
Blood and lymphatic system disorders             
Anaemia * 1  1/154 (0.65%)  9/155 (5.81%)  5/152 (3.29%)  2/154 (1.30%)  10/155 (6.45%)  6/152 (3.95%) 
Coagulopathy * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  1/152 (0.66%) 
Haemorrhagic anaemia * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Microcytic anaemia * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Nephrogenic anaemia * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Normochromic normocytic anaemia * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Cardiac disorders             
Acute coronary syndrome * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Acute myocardial infarction * 1  3/154 (1.95%)  2/155 (1.29%)  2/152 (1.32%)  4/154 (2.60%)  2/155 (1.29%)  3/152 (1.97%) 
Angina pectoris * 1  1/154 (0.65%)  1/155 (0.65%)  1/152 (0.66%)  1/154 (0.65%)  1/155 (0.65%)  1/152 (0.66%) 
Angina unstable * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  2/152 (1.32%) 
Arteriosclerosis coronary artery * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Atrial fibrillation * 1  0/154 (0.00%)  1/155 (0.65%)  3/152 (1.97%)  0/154 (0.00%)  2/155 (1.29%)  4/152 (2.63%) 
Atrial flutter * 1  0/154 (0.00%)  1/155 (0.65%)  1/152 (0.66%)  0/154 (0.00%)  1/155 (0.65%)  1/152 (0.66%) 
Atrioventricular block complete * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  1/152 (0.66%) 
Bradycardia * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Cardiac arrest * 1  2/154 (1.30%)  1/155 (0.65%)  1/152 (0.66%)  3/154 (1.95%)  2/155 (1.29%)  1/152 (0.66%) 
Cardiac failure * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  1/152 (0.66%) 
Cardiac failure acute * 1  4/154 (2.60%)  1/155 (0.65%)  0/152 (0.00%)  4/154 (2.60%)  2/155 (1.29%)  1/152 (0.66%) 
Cardiac failure chronic * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Cardiac failure congestive * 1  5/154 (3.25%)  9/155 (5.81%)  5/152 (3.29%)  6/154 (3.90%)  11/155 (7.10%)  6/152 (3.95%) 
Cor pulmonale chronic * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Coronary artery disease * 1  2/154 (1.30%)  4/155 (2.58%)  2/152 (1.32%)  2/154 (1.30%)  5/155 (3.23%)  4/152 (2.63%) 
Coronary artery occlusion * 1  0/154 (0.00%)  0/155 (0.00%)  2/152 (1.32%)  0/154 (0.00%)  0/155 (0.00%)  2/152 (1.32%) 
Coronary artery stenosis * 1  3/154 (1.95%)  4/155 (2.58%)  5/152 (3.29%)  3/154 (1.95%)  4/155 (2.58%)  5/152 (3.29%) 
Coronary ostial stenosis * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Ischaemic cardiomyopathy * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Mitral valve incompetence * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Myocardial infarction * 1  3/154 (1.95%)  5/155 (3.23%)  3/152 (1.97%)  3/154 (1.95%)  4/155 (2.58%)  2/152 (1.32%) 
Myocardial ischaemia * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Pericardial effusion * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Right ventricular failure * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Supraventricular tachycardia * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  0/155 (0.00%)  2/152 (1.32%) 
Systolic dysfunction * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Ventricular fibrillation * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Ventricular tachycardia * 1  1/154 (0.65%)  0/155 (0.00%)  1/152 (0.66%)  1/154 (0.65%)  0/155 (0.00%)  1/152 (0.66%) 
Ear and labyrinth disorders             
Vertigo positional * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Eye disorders             
Cataract * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  2/154 (1.30%)  0/155 (0.00%)  1/152 (0.66%) 
Cataract * 1 [1]  1/154 (0.65%)  4/155 (2.58%)  0/152 (0.00%)  1/154 (0.65%)  4/155 (2.58%)  0/152 (0.00%) 
Cataract subcapsular * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Cataract subcapsular * 1 [1]  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Corneal epithelium defect * 1 [1]  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Diabetic retinal oedema * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Diabetic retinal oedema * 1 [1]  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Diabetic retinopathy * 1 [1]  2/154 (1.30%)  0/155 (0.00%)  0/152 (0.00%)  2/154 (1.30%)  0/155 (0.00%)  0/152 (0.00%) 
Diabetic retinopathy * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Hyphaema * 1 [1]  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Intraocular pressure increased * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Iris neovascularisation * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Lens dislocation * 1 [1]  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Macular ischaemia * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Punctate keratitis * 1 [1]  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Punctate keratitis * 1 [1]  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Retinal aneurysm * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Retinal artery occlusion * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Retinal artery occlusion * 1 [1]  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Retinal detachment * 1  1/154 (0.65%)  2/155 (1.29%)  1/152 (0.66%)  2/154 (1.30%)  3/155 (1.94%)  0/152 (0.00%) 
Retinal detachment * 1 [1]  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  3/155 (1.94%)  0/152 (0.00%) 
Retinal haemorrhage * 1 [1]  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Retinal haemorrhage * 1  1/154 (0.65%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Retinal ischaemia * 1 [1]  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Retinal ischaemia * 1 [1]  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Retinal neovascularisation * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Retinal tear * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  1/152 (0.66%) 
Retinal vascular disorder * 1 [1]  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  2/155 (1.29%)  0/152 (0.00%) 
Retinal vein occlusion * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  1/155 (0.65%)  1/152 (0.66%) 
Visual acuity reduced * 1  1/154 (0.65%)  1/155 (0.65%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Visual acuity reduced * 1 [1]  0/154 (0.00%)  1/155 (0.65%)  1/152 (0.66%)  0/154 (0.00%)  1/155 (0.65%)  1/152 (0.66%) 
Vitreous haemorrhage * 1 [1]  3/154 (1.95%)  2/155 (1.29%)  1/152 (0.66%)  3/154 (1.95%)  3/155 (1.94%)  2/152 (1.32%) 
Vitreous haemorrhage * 1  2/154 (1.30%)  7/155 (4.52%)  2/152 (1.32%)  3/154 (1.95%)  9/155 (5.81%)  4/152 (2.63%) 
Vitreous haemorrhage * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  3/154 (1.95%)  9/155 (5.81%)  4/152 (2.63%) 
Vitreous opacities * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Gastrointestinal disorders             
Abdominal hernia * 1  1/154 (0.65%)  1/155 (0.65%)  0/152 (0.00%)  1/154 (0.65%)  1/155 (0.65%)  0/152 (0.00%) 
Colitis * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  1/152 (0.66%) 
Colitis ischaemic * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Constipation * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Diabetic gastroparesis * 1  2/154 (1.30%)  0/155 (0.00%)  0/152 (0.00%)  2/154 (1.30%)  0/155 (0.00%)  0/152 (0.00%) 
Diarrhoea * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  2/154 (1.30%)  0/155 (0.00%)  0/152 (0.00%) 
Diverticulum * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Gastric ulcer haemorrhage * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Gastrointestinal haemorrhage * 1  2/154 (1.30%)  3/155 (1.94%)  1/152 (0.66%)  2/154 (1.30%)  4/155 (2.58%)  1/152 (0.66%) 
Gastrooesophageal reflux disease * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  2/152 (1.32%) 
Haematemesis * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Hiatus hernia * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Ileus * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Impaired gastric emptying * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Internal hernia * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Mallory-Weiss syndrome * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Nausea * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Oesophageal ulcer * 1  1/154 (0.65%)  0/155 (0.00%)  1/152 (0.66%)  1/154 (0.65%)  0/155 (0.00%)  1/152 (0.66%) 
Oesophagitis * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Pancreatitis * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  2/154 (1.30%)  1/155 (0.65%)  0/152 (0.00%) 
Pancreatitis acute * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Retroperitoneal haemorrhage * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Small intestinal obstruction * 1  2/154 (1.30%)  0/155 (0.00%)  0/152 (0.00%)  2/154 (1.30%)  0/155 (0.00%)  0/152 (0.00%) 
Volvulus of small bowel * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
General disorders             
Asthenia * 1  0/154 (0.00%)  0/155 (0.00%)  2/152 (1.32%)  0/154 (0.00%)  0/155 (0.00%)  2/152 (1.32%) 
Chest pain * 1  3/154 (1.95%)  1/155 (0.65%)  4/152 (2.63%)  4/154 (2.60%)  1/155 (0.65%)  4/152 (2.63%) 
Death * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Device failure * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Device malfunction * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Drug withdrawal syndrome * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Generalised oedema * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Medical device complication * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Multi-organ failure * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  2/154 (1.30%)  0/155 (0.00%)  0/152 (0.00%) 
Non-cardiac chest pain * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Oedema peripheral * 1  2/154 (1.30%)  0/155 (0.00%)  1/152 (0.66%)  2/154 (1.30%)  0/155 (0.00%)  1/152 (0.66%) 
Pyrexia * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Sudden cardiac death * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Systemic inflammatory response syndrome * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  2/155 (1.29%)  0/152 (0.00%) 
Hepatobiliary disorders             
Cholecystitis acute * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  1/155 (0.65%)  0/152 (0.00%) 
Cholecystitis chronic * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  1/152 (0.66%) 
Cholelithiasis * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  2/154 (1.30%)  0/155 (0.00%)  1/152 (0.66%) 
Gallbladder cholesterolosis * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Infections and infestations             
Abscess limb * 1  2/154 (1.30%)  2/155 (1.29%)  2/152 (1.32%)  2/154 (1.30%)  2/155 (1.29%)  2/152 (1.32%) 
Appendicitis * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  1/152 (0.66%) 
Appendicitis perforated * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Arthritis bacterial * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Breast cellulitis * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Bronchitis * 1  1/154 (0.65%)  1/155 (0.65%)  1/152 (0.66%)  1/154 (0.65%)  2/155 (1.29%)  1/152 (0.66%) 
Burn infection * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Cellulitis * 1  4/154 (2.60%)  7/155 (4.52%)  8/152 (5.26%)  5/154 (3.25%)  9/155 (5.81%)  8/152 (5.26%) 
Chronic sinusitis * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Clostridium difficile infection * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Diabetic foot infection * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  2/155 (1.29%)  0/152 (0.00%) 
Diverticulitis * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Endocarditis bacterial * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Endophthalmitis * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Endophthalmitis * 1 [1]  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  1/152 (0.66%) 
Enterococcal bacteraemia * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Escherichia urinary tract infection * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Gangrene * 1  0/154 (0.00%)  2/155 (1.29%)  1/152 (0.66%)  2/154 (1.30%)  2/155 (1.29%)  2/152 (1.32%) 
Gastroenteritis * 1  1/154 (0.65%)  1/155 (0.65%)  2/152 (1.32%)  1/154 (0.65%)  1/155 (0.65%)  2/152 (1.32%) 
Gastroenteritis viral * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Infected skin ulcer * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Infection * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Influenza * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Klebsiella sepsis * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Lobar pneumonia * 1  1/154 (0.65%)  1/155 (0.65%)  0/152 (0.00%)  1/154 (0.65%)  3/155 (1.94%)  0/152 (0.00%) 
Localised infection * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Mastoiditis * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Osteomyelitis * 1  3/154 (1.95%)  5/155 (3.23%)  2/152 (1.32%)  5/154 (3.25%)  7/155 (4.52%)  3/152 (1.97%) 
Osteomyelitis acute * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Parotitis * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Perineal abscess * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Pneumonia * 1  4/154 (2.60%)  4/155 (2.58%)  3/152 (1.97%)  4/154 (2.60%)  6/155 (3.87%)  4/152 (2.63%) 
Pneumonia bacterial * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Pyelonephritis * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Sepsis * 1  2/154 (1.30%)  2/155 (1.29%)  0/152 (0.00%)  2/154 (1.30%)  3/155 (1.94%)  0/152 (0.00%) 
Sinusitis * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Staphylococcal bacteraemia * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Staphylococcal infection * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Staphylococcal sepsis * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Urinary tract infection * 1  2/154 (1.30%)  0/155 (0.00%)  0/152 (0.00%)  4/154 (2.60%)  2/155 (1.29%)  1/152 (0.66%) 
Urosepsis * 1  1/154 (0.65%)  2/155 (1.29%)  1/152 (0.66%)  1/154 (0.65%)  2/155 (1.29%)  1/152 (0.66%) 
Wound sepsis * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Injury, poisoning and procedural complications             
Accident * 1  1/154 (0.65%)  1/155 (0.65%)  0/152 (0.00%)  1/154 (0.65%)  1/155 (0.65%)  0/152 (0.00%) 
Accidental overdose * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Ankle fracture * 1  0/154 (0.00%)  1/155 (0.65%)  1/152 (0.66%)  0/154 (0.00%)  1/155 (0.65%)  2/152 (1.32%) 
Arteriovenous fistula site complication * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Arteriovenous fistula site haemorrhage * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Arteriovenous graft site haemorrhage * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Cataract operation complication * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Cataract traumatic * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Clavical fracture * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Concussion * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Craniocerebral injury * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Fall * 1  2/154 (1.30%)  3/155 (1.94%)  5/152 (3.29%)  3/154 (1.95%)  3/155 (1.94%)  5/152 (3.29%) 
Femoral neck fracture * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Femur fracture * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Humerus fracture * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Incisional hernia * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Laceration * 1  0/154 (0.00%)  2/155 (1.29%)  0/152 (0.00%)  0/154 (0.00%)  2/155 (1.29%)  0/152 (0.00%) 
Lower limb fracture * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Lumbar vertebral fracture * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Meniscus injury * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Pelvic fracture * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Procedural pain * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Radius fracture * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Rib fracture * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Road traffic accident * 1  1/154 (0.65%)  2/155 (1.29%)  1/152 (0.66%)  1/154 (0.65%)  2/155 (1.29%)  1/152 (0.66%) 
Seroma * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Spinal compression fracture * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Spinal fracture * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Subdural haematoma * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Thoracic vertebral fracture * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Ulna fracture * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Wound haemorrhage * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Investigations             
Blood creatinine increased * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Haematocrit decreased * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Haemoglobin decreased * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  1/154 (0.65%)  0/155 (0.00%)  1/152 (0.66%) 
Heart rate increased * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
International normalised ratio increased * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Intraocular pressure increased * 1 [1]  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Transaminases increased * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Troponin increased * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Visual acuity tests abnormal * 1 [1]  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%) 
Metabolism and nutrition disorders             
Dehydration * 1  1/154 (0.65%)  2/155 (1.29%)  2/152 (1.32%)  4/154 (2.60%)  2/155 (1.29%)  2/152 (1.32%) 
Diabetes mellitus inadequate control * 1  0/154 (0.00%)  3/155 (1.94%)  2/152 (1.32%)  0/154 (0.00%)  4/155 (2.58%)  2/152 (1.32%) 
Diabetes with hyperosmolarity * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Diabetic ketoacidosis * 1  1/154 (0.65%)  2/155 (1.29%)  2/152 (1.32%)  1/154 (0.65%)  2/155 (1.29%)  2/152 (1.32%) 
Failure to thrive * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Fluid overload * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  1/155 (0.65%)  1/152 (0.66%) 
Fluid retention * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Hyperglycaemia * 1  1/154 (0.65%)  1/155 (0.65%)  0/152 (0.00%)  2/154 (1.30%)  1/155 (0.65%)  0/152 (0.00%) 
Hyperkalaemia * 1  4/154 (2.60%)  3/155 (1.94%)  1/152 (0.66%)  6/154 (3.90%)  4/155 (2.58%)  1/152 (0.66%) 
Hypoglycaemia * 1  1/154 (0.65%)  5/155 (3.23%)  0/152 (0.00%)  1/154 (0.65%)  6/155 (3.87%)  0/152 (0.00%) 
Hypokalaemia * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Ketosis * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Metabolic acidosis * 1  1/154 (0.65%)  1/155 (0.65%)  0/152 (0.00%)  1/154 (0.65%)  1/155 (0.65%)  0/152 (0.00%) 
Obesity * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Musculoskeletal and connective tissue disorders             
Arthralgia * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%) 
Arthritis * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Back pain * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  2/154 (1.30%)  1/155 (0.65%)  0/152 (0.00%) 
Cervical spinal stenosis * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Intervertebral disc degeneration * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  2/155 (1.29%)  0/152 (0.00%) 
Intervertebral disc protrusion * 1  0/154 (0.00%)  1/155 (0.65%)  2/152 (1.32%)  0/154 (0.00%)  1/155 (0.65%)  2/152 (1.32%) 
Joint effusion * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Musculoskeletal chest pain * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Neuropathic arthropathy * 1  0/154 (0.00%)  2/155 (1.29%)  0/152 (0.00%)  0/154 (0.00%)  2/155 (1.29%)  0/152 (0.00%) 
Osteoarthritis * 1  3/154 (1.95%)  4/155 (2.58%)  0/152 (0.00%)  3/154 (1.95%)  5/155 (3.23%)  0/152 (0.00%) 
Spinal column stenosis * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Spinal osteoarthritis * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Tendon disorder * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Tendonitits * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Adenocarcinoma gastric * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Bladder cancer stage II * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Breast cancer * 1  0/154 (0.00%)  3/155 (1.94%)  0/152 (0.00%)  0/154 (0.00%)  3/155 (1.94%)  0/152 (0.00%) 
Breast cancer metastatic * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Chronic myeloid leukaemia * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Chronic myelomonocytic leukaemia * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Clear cell renal cell carcinoma * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Diffuse large B-cell lymphoma stage III * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Invasive ductal breast carcinoma * 1  0/154 (0.00%)  1/155 (0.65%)  3/152 (1.97%)  0/154 (0.00%)  1/155 (0.65%)  3/152 (1.97%) 
Malignant melanoma * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Melanocytic naevus * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%) 
Myelodysplastic syndrome * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Prostate cancer * 1  0/154 (0.00%)  3/155 (1.94%)  0/152 (0.00%)  0/154 (0.00%)  3/155 (1.94%)  1/152 (0.66%) 
Prostate cancer recurrent * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Rectal adenocarcinoma * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Rectal neoplasm * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Renal cancer * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Squamous cell carcinoma of skin * 1  0/154 (0.00%)  1/155 (0.65%)  2/152 (1.32%)  0/154 (0.00%)  1/155 (0.65%)  2/152 (1.32%) 
Nervous system disorders             
Amnesia * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Ataxia * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Autonomic nervous system imbalance * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Brain injury * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Brain stem stroke * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Carotid artery stenosis * 1  0/154 (0.00%)  2/155 (1.29%)  0/152 (0.00%)  0/154 (0.00%)  2/155 (1.29%)  0/152 (0.00%) 
Cerebral infarction * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Cerebrovascular accident * 1  2/154 (1.30%)  5/155 (3.23%)  5/152 (3.29%)  4/154 (2.60%)  5/155 (3.23%)  5/152 (3.29%) 
Cognitive disorder * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Coma * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Convulsion * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  2/154 (1.30%)  1/155 (0.65%)  1/152 (0.66%) 
Diabetic coma * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Dizziness * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Encephalopathy * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  1/155 (0.65%)  0/152 (0.00%) 
Haemorrhage intracranial * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Headache * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Hemianopia homonymous * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Hypertensive encephalopathy * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Ischaemic cerebral infarction * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Ischaemic stroke * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  1/152 (0.66%) 
Lacunar infarction * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Lumbar radiculopathy * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Metabolic encephalopathy * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Multiple sclerosis * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Normal pressure hydrocephalus * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Presyncope * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Sciatica * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Sedation * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Syncope * 1  2/154 (1.30%)  2/155 (1.29%)  0/152 (0.00%)  3/154 (1.95%)  3/155 (1.94%)  1/152 (0.66%) 
Thalamic infarction * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Toxic encephalopathy * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Transient ischaemic attack * 1  3/154 (1.95%)  0/155 (0.00%)  1/152 (0.66%)  3/154 (1.95%)  1/155 (0.65%)  1/152 (0.66%) 
VIIth nerve paralysis * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Visual field defect * 1 [1]  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Psychiatric disorders             
Affective disorder * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Confusional state * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Depression * 1  2/154 (1.30%)  1/155 (0.65%)  0/152 (0.00%)  2/154 (1.30%)  1/155 (0.65%)  0/152 (0.00%) 
Disorientation * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Mental status changes * 1  0/154 (0.00%)  2/155 (1.29%)  1/152 (0.66%)  0/154 (0.00%)  2/155 (1.29%)  1/152 (0.66%) 
Schizoaffective disorder * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Renal and urinary disorders             
Azotaemia * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Bladder outlet obstruction * 1  1/154 (0.65%)  1/155 (0.65%)  0/152 (0.00%)  1/154 (0.65%)  1/155 (0.65%)  0/152 (0.00%) 
Calculus ureteric * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Haematuria * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Intercapillary glomerulosclerosis * 1  0/154 (0.00%)  1/155 (0.65%)  1/152 (0.66%)  0/154 (0.00%)  1/155 (0.65%)  1/152 (0.66%) 
Nephrolithiasis * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Nephropathy * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Nephropathy toxic * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Nephrosclerosis * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Nephrotic syndrome * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Renal failure * 1  4/154 (2.60%)  5/155 (3.23%)  1/152 (0.66%)  5/154 (3.25%)  5/155 (3.23%)  1/152 (0.66%) 
Renal failure acute * 1  7/154 (4.55%)  6/155 (3.87%)  6/152 (3.95%)  9/154 (5.84%)  10/155 (6.45%)  8/152 (5.26%) 
Renal failure chronic * 1  2/154 (1.30%)  4/155 (2.58%)  3/152 (1.97%)  4/154 (2.60%)  5/155 (3.23%)  3/152 (1.97%) 
Renal impairment * 1  1/154 (0.65%)  1/155 (0.65%)  0/152 (0.00%)  1/154 (0.65%)  1/155 (0.65%)  0/152 (0.00%) 
Renal tubular necrosis * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Ureteric stenosis * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Urinary retention * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  1/154 (0.65%)  1/155 (0.65%)  0/152 (0.00%) 
Reproductive system and breast disorders             
Breast mass * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%) 
Endometrial hyperplasia * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Labia enlarged * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Menorrhagia * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Postmenopausal haemorrhage * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Uterine mass * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  1/152 (0.66%) 
Respiratory, thoracic and mediastinal disorders             
Acute pulmonary oedema * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Acute respiratory failure * 1  0/154 (0.00%)  1/155 (0.65%)  1/152 (0.66%)  2/154 (1.30%)  2/155 (1.29%)  1/152 (0.66%) 
Asthma * 1  1/154 (0.65%)  1/155 (0.65%)  0/152 (0.00%)  1/154 (0.65%)  1/155 (0.65%)  0/152 (0.00%) 
Atelectasis * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Bronchiectasis * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Chronic obstructive pulmonary disease * 1  2/154 (1.30%)  0/155 (0.00%)  0/152 (0.00%)  2/154 (1.30%)  0/155 (0.00%)  0/152 (0.00%) 
Dyspnoea * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Hypoxia * 1  0/154 (0.00%)  2/155 (1.29%)  0/152 (0.00%)  1/154 (0.65%)  1/155 (0.65%)  0/152 (0.00%) 
Pleural effusion * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  1/155 (0.65%)  0/152 (0.00%) 
Pulmonary embolism * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  1/154 (0.65%)  1/155 (0.65%)  0/152 (0.00%) 
Pulmonary fibrosis * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Pulmonary oedema * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Respiratory distress * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Skin and subcutaneous tissue disorders             
Decubitus ulcer * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Diabetic foot * 1  0/154 (0.00%)  2/155 (1.29%)  2/152 (1.32%)  0/154 (0.00%)  3/155 (1.94%)  2/152 (1.32%) 
Hypertrophic scar * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Skin ulcer * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  1/154 (0.65%)  1/155 (0.65%)  1/152 (0.66%) 
Surgical and medical procedures             
Arteriovenous fistula operation * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Coronary artery bypass * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%) 
Foot amputation * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Vascular disorders             
Arteriosclerosis * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Deep vein thrombosis * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Haematoma * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Hypertension * 1  3/154 (1.95%)  5/155 (3.23%)  1/152 (0.66%)  3/154 (1.95%)  6/155 (3.87%)  2/152 (1.32%) 
Hypertensive crisis * 1  2/154 (1.30%)  2/155 (1.29%)  0/152 (0.00%)  2/154 (1.30%)  2/155 (1.29%)  0/152 (0.00%) 
Hypertensive emergency * 1  1/154 (0.65%)  1/155 (0.65%)  0/152 (0.00%)  1/154 (0.65%)  1/155 (0.65%)  0/152 (0.00%) 
Hypotension * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  1/154 (0.65%)  2/155 (1.29%)  0/152 (0.00%) 
Hypovolaemic shock * 1  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%)  1/154 (0.65%)  0/155 (0.00%)  0/152 (0.00%) 
Intermittent claudication * 1  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Malignant hypertension * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  1/154 (0.65%)  1/155 (0.65%)  1/152 (0.66%) 
Orthostatic hypotension * 1  2/154 (1.30%)  1/155 (0.65%)  0/152 (0.00%)  2/154 (1.30%)  1/155 (0.65%)  0/152 (0.00%) 
Peripheral arterial occlusive disease * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Peripheral artery stenosis * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
Peripheral ischaemia * 1  0/154 (0.00%)  0/155 (0.00%)  0/152 (0.00%)  0/154 (0.00%)  1/155 (0.65%)  0/152 (0.00%) 
Peripheral vascular disorder * 1  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%)  0/154 (0.00%)  0/155 (0.00%)  1/152 (0.66%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 16.1
[1]
Study eye
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Control (Week 0 to Week 100) IAI;EYLEA®;BAY86-5321 2Q4 (Week 0 to Week 100) IAI;EYLEA®;BAY86-5321) 2Q8 (Week 0 to Week 100) Control (Week 0 to Week 148) IAI;EYLEA®;BAY86-5321 2Q4 (Week 0 to Week 148) IAI;EYLEA®;BAY86-5321) 2Q8 (Week 0 to Week 148)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   91/154 (59.09%)   90/155 (58.06%)   76/152 (50.00%)   134/154 (87.01%)   137/155 (88.39%)   136/152 (89.47%) 
Blood and lymphatic system disorders             
Anaemia * 1  12/154 (7.79%)  20/155 (12.90%)  12/152 (7.89%)  15/154 (9.74%)  27/155 (17.42%)  20/152 (13.16%) 
Cardiac disorders             
Cardiac failure congestive * 1  6/154 (3.90%)  12/155 (7.74%)  9/152 (5.92%)  4/154 (2.60%)  6/155 (3.87%)  8/152 (5.26%) 
Endocrine disorders             
Hypothyroidism * 1  7/154 (4.55%)  4/155 (2.58%)  5/152 (3.29%)  8/154 (5.19%)  4/155 (2.58%)  5/152 (3.29%) 
Eye disorders             
Cataract * 1  17/154 (11.04%)  15/155 (9.68%)  11/152 (7.24%)  25/154 (16.23%)  22/155 (14.19%)  17/152 (11.18%) 
Cataract * 1 [1]  16/154 (10.39%)  21/155 (13.55%)  13/152 (8.55%)  24/154 (15.58%)  28/155 (18.06%)  21/152 (13.82%) 
Cataract cortical * 1 [1]  6/154 (3.90%)  3/155 (1.94%)  6/152 (3.95%)  11/154 (7.14%)  2/155 (1.29%)  7/152 (4.61%) 
Cataract cortical * 1  8/154 (5.19%)  2/155 (1.29%)  7/152 (4.61%)  8/154 (5.19%)  5/155 (3.23%)  7/152 (4.61%) 
Cataract nuclear * 1 [1]  2/154 (1.30%)  6/155 (3.87%)  2/152 (1.32%)  6/154 (3.90%)  8/155 (5.16%)  3/152 (1.97%) 
Cataract nuclear * 1  2/154 (1.30%)  6/155 (3.87%)  2/152 (1.32%)  2/154 (1.30%)  8/155 (5.16%)  2/152 (1.32%) 
Cataract subcapsular * 1  6/154 (3.90%)  4/155 (2.58%)  8/152 (5.26%)  8/154 (5.19%)  8/155 (5.16%)  10/152 (6.58%) 
Cataract subcapsular * 1 [1]  7/154 (4.55%)  6/155 (3.87%)  8/152 (5.26%)  10/154 (6.49%)  12/155 (7.74%)  10/152 (6.58%) 
Conjunctival haemorrhage * 1  29/154 (18.83%)  30/155 (19.35%)  27/152 (17.76%)  31/154 (20.13%)  35/155 (22.58%)  29/152 (19.08%) 
Conjunctival haemorrhage * 1 [1]  53/154 (34.42%)  63/155 (40.65%)  48/152 (31.58%)  55/154 (35.71%)  63/155 (40.65%)  50/152 (32.89%) 
Corneal abrasion * 1 [1]  6/154 (3.90%)  4/155 (2.58%)  6/152 (3.95%)  9/154 (5.84%)  7/155 (4.52%)  6/152 (3.95%) 
Diabetic retinal oedema * 1  19/154 (12.34%)  22/155 (14.19%)  18/152 (11.84%)  26/154 (16.88%)  29/155 (18.71%)  23/152 (15.13%) 
Diabetic retinopathy * 1  11/154 (7.14%)  8/155 (5.16%)  14/152 (9.21%)  16/154 (10.39%)  8/155 (5.16%)  18/152 (11.84%) 
Dry eye * 1  7/154 (4.55%)  12/155 (7.74%)  7/152 (4.61%)  8/154 (5.19%)  13/155 (8.39%)  9/152 (5.92%) 
Dry eye * 1 [1]  10/154 (6.49%)  14/155 (9.03%)  7/152 (4.61%)  12/154 (7.79%)  16/155 (10.32%)  9/152 (5.92%) 
Eye irritation * 1 [1]  12/154 (7.79%)  15/155 (9.68%)  11/152 (7.24%)  14/154 (9.09%)  15/155 (9.68%)  13/152 (8.55%) 
Eye irritation * 1  7/154 (4.55%)  6/155 (3.87%)  7/152 (4.61%)  8/154 (5.19%)  9/155 (5.81%)  8/152 (5.26%) 
Eye pain * 1 [1]  20/154 (12.99%)  23/155 (14.84%)  21/152 (13.82%)  23/154 (14.94%)  23/155 (14.84%)  26/152 (17.11%) 
Eye pain * 1  7/154 (4.55%)  11/155 (7.10%)  9/152 (5.92%)  10/154 (6.49%)  13/155 (8.39%)  14/152 (9.21%) 
Foreign body sensation in eyes * 1 [1]  8/154 (5.19%)  8/155 (5.16%)  5/152 (3.29%)  8/154 (5.19%)  9/155 (5.81%)  6/152 (3.95%) 
Lacrimation increased * 1  3/154 (1.95%)  4/155 (2.58%)  7/152 (4.61%)  4/154 (2.60%)  5/155 (3.23%)  9/152 (5.92%) 
Lacrimation increased * 1 [1]  6/154 (3.90%)  7/155 (4.52%)  6/152 (3.95%)  7/154 (4.55%)  8/155 (5.16%)  8/152 (5.26%) 
Macular fibrosis * 1 [1]  15/154 (9.74%)  11/155 (7.10%)  15/152 (9.87%)  20/154 (12.99%)  13/155 (8.39%)  17/152 (11.18%) 
Macular fibrosis * 1  12/154 (7.79%)  11/155 (7.10%)  16/152 (10.53%)  19/154 (12.34%)  14/155 (9.03%)  23/152 (15.13%) 
Macular oedema * 1  1/154 (0.65%)  4/155 (2.58%)  6/152 (3.95%)  7/154 (4.55%)  6/155 (3.87%)  9/152 (5.92%) 
Ocular hyperaemia * 1 [1]  12/154 (7.79%)  6/155 (3.87%)  6/152 (3.95%)  12/154 (7.79%)  6/155 (3.87%)  7/152 (4.61%) 
Pain in extremity * 1  10/154 (6.49%)  8/155 (5.16%)  5/152 (3.29%)  13/154 (8.44%)  12/155 (7.74%)  7/152 (4.61%) 
Photopsia * 1 [1]  7/154 (4.55%)  2/155 (1.29%)  1/152 (0.66%)  8/154 (5.19%)  2/155 (1.29%)  2/152 (1.32%) 
Posterior capsule opacification * 1  10/154 (6.49%)  5/155 (3.23%)  5/152 (3.29%)  12/154 (7.79%)  8/155 (5.16%)  10/152 (6.58%) 
Posterior capsule opacification * 1 [1]  12/154 (7.79%)  7/155 (4.52%)  8/152 (5.26%)  16/154 (10.39%)  9/155 (5.81%)  15/152 (9.87%) 
Punctate keratitis * 1 [1]  1/154 (0.65%)  5/155 (3.23%)  7/152 (4.61%)  3/154 (1.95%)  8/155 (5.16%)  7/152 (4.61%) 
Retinal exudates * 1 [1]  13/154 (8.44%)  12/155 (7.74%)  4/152 (2.63%)  14/154 (9.09%)  15/155 (9.68%)  6/152 (3.95%) 
Retinal exudates * 1  11/154 (7.14%)  12/155 (7.74%)  6/152 (3.95%)  15/154 (9.74%)  15/155 (9.68%)  8/152 (5.26%) 
Retinal haemorrhage * 1 [1]  15/154 (9.74%)  10/155 (6.45%)  5/152 (3.29%)  16/154 (10.39%)  13/155 (8.39%)  7/152 (4.61%) 
Retinal haemorrhage * 1  10/154 (6.49%)  11/155 (7.10%)  5/152 (3.29%)  13/154 (8.44%)  16/155 (10.32%)  6/152 (3.95%) 
Retinal neovascularisation * 1  10/154 (6.49%)  10/155 (6.45%)  4/152 (2.63%)  12/154 (7.79%)  10/155 (6.45%)  5/152 (3.29%) 
Retinal neovascularisation * 1 [1]  12/154 (7.79%)  3/155 (1.94%)  3/152 (1.97%)  12/154 (7.79%)  3/155 (1.94%)  3/152 (1.97%) 
Retinal pigment epitheliopathy * 1 [1]  3/154 (1.95%)  5/155 (3.23%)  8/152 (5.26%)  3/154 (1.95%)  6/155 (3.87%)  9/152 (5.92%) 
Vision blurred * 1 [1]  10/154 (6.49%)  11/155 (7.10%)  6/152 (3.95%)  13/154 (8.44%)  14/155 (9.03%)  9/152 (5.92%) 
Vision blurred * 1  5/154 (3.25%)  8/155 (5.16%)  5/152 (3.29%)  7/154 (4.55%)  11/155 (7.10%)  7/152 (4.61%) 
Visual Impairment * 1 [1]  7/154 (4.55%)  1/155 (0.65%)  3/152 (1.97%)  8/154 (5.19%)  1/155 (0.65%)  3/152 (1.97%) 
Visual acuity reduced * 1  6/154 (3.90%)  4/155 (2.58%)  10/152 (6.58%)  10/154 (6.49%)  8/155 (5.16%)  10/152 (6.58%) 
Visual acuity reduced * 1 [1]  11/154 (7.14%)  7/155 (4.52%)  10/152 (6.58%)  14/154 (9.09%)  10/155 (6.45%)  12/152 (7.89%) 
Vitreous detachment * 1  16/154 (10.39%)  15/155 (9.68%)  18/152 (11.84%)  23/154 (14.94%)  17/155 (10.97%)  23/152 (15.13%) 
Vitreous detachment * 1 [1]  15/154 (9.74%)  14/155 (9.03%)  22/152 (14.47%)  20/154 (12.99%)  20/155 (12.90%)  25/152 (16.45%) 
Vitreous floaters * 1  10/154 (6.49%)  11/155 (7.10%)  10/152 (6.58%)  12/154 (7.79%)  15/155 (9.68%)  14/152 (9.21%) 
Vitreous floaters * 1 [1]  14/154 (9.09%)  21/155 (13.55%)  17/152 (11.18%)  16/154 (10.39%)  23/155 (14.84%)  21/152 (13.82%) 
Vitreous haemorrhage * 1 [1]  12/154 (7.79%)  9/155 (5.81%)  2/152 (1.32%)  13/154 (8.44%)  10/155 (6.45%)  4/152 (2.63%) 
Vitreous haemorrhage * 1  11/154 (7.14%)  8/155 (5.16%)  5/152 (3.29%)  19/154 (12.34%)  11/155 (7.10%)  7/152 (4.61%) 
Gastrointestinal disorders             
Constipation * 1  9/154 (5.84%)  11/155 (7.10%)  5/152 (3.29%)  14/154 (9.09%)  15/155 (9.68%)  6/152 (3.95%) 
Diarrhoea * 1  13/154 (8.44%)  14/155 (9.03%)  6/152 (3.95%)  15/154 (9.74%)  19/155 (12.26%)  7/152 (4.61%) 
Gastrooesophageal reflux disease * 1  9/154 (5.84%)  10/155 (6.45%)  4/152 (2.63%)  14/154 (9.09%)  13/155 (8.39%)  10/152 (6.58%) 
Nausea * 1  15/154 (9.74%)  19/155 (12.26%)  11/152 (7.24%)  16/154 (10.39%)  21/155 (13.55%)  16/152 (10.53%) 
Vomiting * 1  7/154 (4.55%)  14/155 (9.03%)  3/152 (1.97%)  9/154 (5.84%)  16/155 (10.32%)  5/152 (3.29%) 
General disorders             
Chest pain * 1  9/154 (5.84%)  3/155 (1.94%)  5/152 (3.29%)  9/154 (5.84%)  3/155 (1.94%)  5/152 (3.29%) 
Fatigue * 1  4/154 (2.60%)  8/155 (5.16%)  3/152 (1.97%)  5/154 (3.25%)  9/155 (5.81%)  3/152 (1.97%) 
Oedema peripheral * 1  8/154 (5.19%)  15/155 (9.68%)  15/152 (9.87%)  11/154 (7.14%)  19/155 (12.26%)  16/152 (10.53%) 
Pyrexia * 1  2/154 (1.30%)  7/155 (4.52%)  6/152 (3.95%)  5/154 (3.25%)  10/155 (6.45%)  7/152 (4.61%) 
Immune system disorders             
Drug hypersensitivity * 1  2/154 (1.30%)  5/155 (3.23%)  3/152 (1.97%)  6/154 (3.90%)  8/155 (5.16%)  3/152 (1.97%) 
Seasonal allergy * 1  8/154 (5.19%)  6/155 (3.87%)  9/152 (5.92%)  9/154 (5.84%)  9/155 (5.81%)  12/152 (7.89%) 
Infections and infestations             
Bronchitis * 1  11/154 (7.14%)  12/155 (7.74%)  4/152 (2.63%)  13/154 (8.44%)  12/155 (7.74%)  7/152 (4.61%) 
Cellulitis * 1  7/154 (4.55%)  10/155 (6.45%)  12/152 (7.89%)  7/154 (4.55%)  5/155 (3.23%)  8/152 (5.26%) 
Ear infection * 1  4/154 (2.60%)  3/155 (1.94%)  6/152 (3.95%)  6/154 (3.90%)  5/155 (3.23%)  9/152 (5.92%) 
Gastroenteritis viral * 1  2/154 (1.30%)  2/155 (1.29%)  6/152 (3.95%)  2/154 (1.30%)  3/155 (1.94%)  8/152 (5.26%) 
Influenza * 1  9/154 (5.84%)  7/155 (4.52%)  16/152 (10.53%)  15/154 (9.74%)  9/155 (5.81%)  22/152 (14.47%) 
Localised infection * 1  5/154 (3.25%)  10/155 (6.45%)  5/152 (3.29%)  11/154 (7.14%)  11/155 (7.10%)  5/152 (3.29%) 
Nasopharyngitis * 1  17/154 (11.04%)  17/155 (10.97%)  19/152 (12.50%)  23/154 (14.94%)  22/155 (14.19%)  24/152 (15.79%) 
Pneumonia * 1  7/154 (4.55%)  8/155 (5.16%)  7/152 (4.61%)  4/154 (2.60%)  9/155 (5.81%)  6/152 (3.95%) 
Sinusitis * 1  12/154 (7.79%)  13/155 (8.39%)  12/152 (7.89%)  18/154 (11.69%)  14/155 (9.03%)  13/152 (8.55%) 
Upper respiratory tract infection * 1  13/154 (8.44%)  11/155 (7.10%)  15/152 (9.87%)  16/154 (10.39%)  13/155 (8.39%)  17/152 (11.18%) 
Urinary tract infection * 1  14/154 (9.09%)  17/155 (10.97%)  26/152 (17.11%)  20/154 (12.99%)  30/155 (19.35%)  32/152 (21.05%) 
Injury, poisoning and procedural complications             
Fall * 1  8/154 (5.19%)  7/155 (4.52%)  12/152 (7.89%)  12/154 (7.79%)  7/155 (4.52%)  14/152 (9.21%) 
Procedural pain * 1  1/154 (0.65%)  8/155 (5.16%)  2/152 (1.32%)  2/154 (1.30%)  8/155 (5.16%)  3/152 (1.97%) 
Investigations             
Blood creatine phosphokinase increased * 1  12/154 (7.79%)  7/155 (4.52%)  4/152 (2.63%)  12/154 (7.79%)  9/155 (5.81%)  4/152 (2.63%) 
Blood glucose increased * 1  6/154 (3.90%)  9/155 (5.81%)  11/152 (7.24%)  9/154 (5.84%)  15/155 (9.68%)  16/152 (10.53%) 
Blood pressure increased * 1  10/154 (6.49%)  9/155 (5.81%)  7/152 (4.61%)  15/154 (9.74%)  12/155 (7.74%)  8/152 (5.26%) 
Blood pressure systolic increased * 1  2/154 (1.30%)  2/155 (1.29%)  5/152 (3.29%)  2/154 (1.30%)  4/155 (2.58%)  8/152 (5.26%) 
Glycosylated haemoglobin increased * 1  7/154 (4.55%)  7/155 (4.52%)  13/152 (8.55%)  10/154 (6.49%)  10/155 (6.45%)  16/152 (10.53%) 
Intraocular pressure increased * 1 [1]  2/154 (1.30%)  12/155 (7.74%)  10/152 (6.58%)  6/154 (3.90%)  16/155 (10.32%)  10/152 (6.58%) 
Urine protein/ creatinine ratio increased * 1  8/154 (5.19%)  5/155 (3.23%)  2/152 (1.32%)  9/154 (5.84%)  8/155 (5.16%)  3/152 (1.97%) 
Metabolism and nutrition disorders             
Diabetes mellitus * 1  20/154 (12.99%)  13/155 (8.39%)  19/152 (12.50%)  28/154 (18.18%)  23/155 (14.84%)  25/152 (16.45%) 
Hypercholesterolaemia * 1  10/154 (6.49%)  5/155 (3.23%)  3/152 (1.97%)  13/154 (8.44%)  6/155 (3.87%)  4/152 (2.63%) 
Hyperkalaemia * 1  9/154 (5.84%)  9/155 (5.81%)  6/152 (3.95%)  9/154 (5.84%)  11/155 (7.10%)  8/152 (5.26%) 
Hypoglycaemia * 1  3/154 (1.95%)  8/155 (5.16%)  5/152 (3.29%)  10/154 (6.49%)  14/155 (9.03%)  9/152 (5.92%) 
Type 2 diabetes mellitus * 1  6/154 (3.90%)  9/155 (5.81%)  5/152 (3.29%)  9/154 (5.84%)  12/155 (7.74%)  6/152 (3.95%) 
Vitamin D deficiency * 1  7/154 (4.55%)  6/155 (3.87%)  5/152 (3.29%)  7/154 (4.55%)  8/155 (5.16%)  7/152 (4.61%) 
Musculoskeletal and connective tissue disorders             
Arthralgia * 1  9/154 (5.84%)  8/155 (5.16%)  8/152 (5.26%)  12/154 (7.79%)  13/155 (8.39%)  9/152 (5.92%) 
Arthritis * 1  6/154 (3.90%)  5/155 (3.23%)  10/152 (6.58%)  7/154 (4.55%)  6/155 (3.87%)  12/152 (7.89%) 
Back pain * 1  8/154 (5.19%)  20/155 (12.90%)  6/152 (3.95%)  11/154 (7.14%)  22/155 (14.19%)  9/152 (5.92%) 
Muscle spasms * 1  8/154 (5.19%)  5/155 (3.23%)  2/152 (1.32%)  9/154 (5.84%)  6/155 (3.87%)  4/152 (2.63%) 
Osteoarthritis * 1  7/154 (4.55%)  7/155 (4.52%)  5/152 (3.29%)  6/154 (3.90%)  4/155 (2.58%)  12/152 (7.89%) 
Nervous system disorders             
Dizziness * 1  8/154 (5.19%)  7/155 (4.52%)  9/152 (5.92%)  9/154 (5.84%)  9/155 (5.81%)  10/152 (6.58%) 
Headache * 1  19/154 (12.34%)  18/155 (11.61%)  7/152 (4.61%)  22/154 (14.29%)  21/155 (13.55%)  13/152 (8.55%) 
Neuropathy peripheral * 1  5/154 (3.25%)  5/155 (3.23%)  7/152 (4.61%)  6/154 (3.90%)  6/155 (3.87%)  8/152 (5.26%) 
Psychiatric disorders             
Anxiety * 1  7/154 (4.55%)  12/155 (7.74%)  4/152 (2.63%)  9/154 (5.84%)  13/155 (8.39%)  5/152 (3.29%) 
Depression * 1  7/154 (4.55%)  7/155 (4.52%)  4/152 (2.63%)  9/154 (5.84%)  6/155 (3.87%)  4/152 (2.63%) 
Renal and urinary disorders             
Renal failure acute * 1  11/154 (7.14%)  10/155 (6.45%)  9/152 (5.92%)  5/154 (3.25%)  8/155 (5.16%)  7/152 (4.61%) 
Renal failure chronic * 1  4/154 (2.60%)  9/155 (5.81%)  8/152 (5.26%)  5/154 (3.25%)  9/155 (5.81%)  8/152 (5.26%) 
Respiratory, thoracic and mediastinal disorders             
Cough * 1  13/154 (8.44%)  18/155 (11.61%)  17/152 (11.18%)  16/154 (10.39%)  21/155 (13.55%)  20/152 (13.16%) 
Dyspnoea * 1  6/154 (3.90%)  12/155 (7.74%)  11/152 (7.24%)  7/154 (4.55%)  15/155 (9.68%)  13/152 (8.55%) 
Vascular disorders             
Hypertension * 1  49/154 (31.82%)  41/155 (26.45%)  42/152 (27.63%)  56/154 (36.36%)  51/155 (32.90%)  49/152 (32.24%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 16.1
[1]
Study eye
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Not less than 45 days prior to submission of any (M)anuscript, (I)nstitution shall, or cause PI to, provide (S)ponsor a copy of (M). (I) to consider comments submitted by (S), & to delete confidential information upon (S) request. At (S)'s request, (I) to delay publication for an additional 60 days to allow filing of patent applications. (I) & PI agree to delay publication, prior to (M) summarizing data from all sites, unless no (M) is published prior to first anniversary of final study report.
Results Point of Contact
Name/Title: Clinical Trial Management
Organization: Regeneron
Phone: 914 847 7000