FAME: Fluocinolone Acetonide Implant Compared to Sham Injection in Patients With Diabetic Macular Edema
Sponsor
Alimera Sciences (Industry)
Overall Status
Completed
CT.gov ID
NCT00344968
Collaborator
(none)
956
1
3
39
24.5
Study Details
Study Description
Brief Summary
This study will evaluate the safety and efficacy of an intravitreal insert of fluocinolone acetonide for the treatment of diabetic macular edema.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
956 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-Masked, Parallel Group, Multi-center, Dose-Finding Comparison of the Safety and Efficacy of ASI-001A 0.5 μg/Day and ASI-001B 0.2 μg/Day Fluocinolone Acetonide Intravitreal Inserts to Sham Injection in Subjects With Diabetic Macular Edema
Study Start Date
:
Sep 1, 2007
Actual Primary Completion Date
:
Dec 1, 2009
Actual Study Completion Date
:
Dec 1, 2010
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1
|
Drug: fluocinolone acetonide
0.5 mg fluocinolone acetonide intravitreal insert
|
| Experimental: 2
|
Drug: Fluocinolone Acetonide
0.2 mg fluocinolone acetonide intravitreal insert
|
| Sham Comparator: 3
|
Procedure: Standard of care laser photocoagulation
Laser photocoagulation
|
Outcome Measures
Primary Outcome Measures
- Visual Acuity [36 months]
The percentage of subjects with an increase from baseline of 15 or more letters in best corrected visual acuity letter score as assessed by ETDRS eye chart (study eye).
Secondary Outcome Measures
- Retinal Thickness [36 months]
Retinal images where sent to a reading center for analysis. Some images were not clear/distorted and could not be properly analyzed. This accounts for the discrepancy in the number of participants analyzed.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Age >= 18 years with diabetic macular edema
-
Diagnosis of diabetes mellitus types 1 or 2
-
Best corrected visual acuity of 19-68 letters
-
Retinal thickness > 250 micron by OCT
-
Investigator is comfortable deferring macular laser treatment for 6 weeks
Exclusion Criteria:
-
Glaucoma, ocular hypertension, IOP >21 mmHg or concurrent therapy at screening with IOP lowering agents
-
Retinal or choroidal neovascularization due to ocular conditions other than diabetic retinopathy
-
Prior intravitreal, subtenon, or periocular steroid therapy within 6 months
-
Any ocular surgery within the last 3 months
-
Retinal laser treatment within the last 3 months
-
History of uncontrolled IOP elevation with steroid use that did not respond to topical therapy
-
Any lens opacity which impairs visualization of the posterior pole
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Atlanta | Georgia | United States |
Sponsors and Collaborators
- Alimera Sciences
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Alimera Sciences
ClinicalTrials.gov Identifier:
NCT00344968
Other Study ID Numbers:
- C-01-05-001
First Posted:
Jun 27, 2006
Last Update Posted:
May 7, 2014
Last Verified:
Apr 1, 2014
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Sham Comparator | Fluocinolone Acetonide: 0.2 ug/Day Implant | Fluocinolone Acetonide: 0.5 ug/Day Implant |
|---|---|---|---|
| Arm/Group Description | Procedure: Standard of care laser photocoagulation | Dose 0.2 ug/day Medidur Implant | Dose 0.5 ug/day Medidur implant |
| Period Title: Overall Study | |||
| STARTED | 185 | 376 | 395 |
| COMPLETED | 126 | 274 | 279 |
| NOT COMPLETED | 59 | 102 | 116 |
Baseline Characteristics
| Arm/Group Title | Sham Comparator | 0.2 ug/Day Implant | 0.5 ug/Day Implant | Total |
|---|---|---|---|---|
| Arm/Group Description | Procedure: Standard of care laser photocoagulation | Dose 0.2 ug/day Medidur Implant | Dose 0.5 ug/day Medidur implant | Total of all reporting groups |
| Overall Participants | 185 | 376 | 395 | 956 |
| Age (participants) [Number] | ||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
119
64.3%
|
213
56.6%
|
232
58.7%
|
564
59%
|
| >=65 years |
66
35.7%
|
162
43.1%
|
161
40.8%
|
389
40.7%
|
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
61.9
(9.6)
|
63.0
(9.3)
|
62.2
(9.3)
|
62.5
(9.4)
|
| Gender (participants) [Number] | ||||
| Female |
77
41.6%
|
160
42.6%
|
150
38%
|
387
40.5%
|
| Male |
108
58.4%
|
215
57.2%
|
243
61.5%
|
566
59.2%
|
| Region of Enrollment (participants) [Number] | ||||
| North America |
129
69.7%
|
259
68.9%
|
274
69.4%
|
662
69.2%
|
| India |
39
21.1%
|
80
21.3%
|
82
20.8%
|
201
21%
|
| Europe |
17
9.2%
|
37
9.8%
|
39
9.9%
|
93
9.7%
|
Outcome Measures
| Title | Visual Acuity |
|---|---|
| Description | The percentage of subjects with an increase from baseline of 15 or more letters in best corrected visual acuity letter score as assessed by ETDRS eye chart (study eye). |
| Time Frame | 36 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Three subjects were randomized but did not receive treatment. These subjects were not included in the safety analysis, which accounts for the discrepancy in the overall number of participants. |
| Arm/Group Title | Sham Comparator | Fluocinolone Acetonide: 0.2 ug/Day Implant | Fluocinolone Acetonide: 0.5 ug/Day Implant |
|---|---|---|---|
| Arm/Group Description | Procedure: Standard of care laser photocoagulation | Dose 0.2 ug/day Medidur implant | Dose 0.5 ug/day Medidur implant |
| Measure Participants | 185 | 376 | 395 |
| Number [percentage of subjects] |
18.9
(18.01)
|
28.7
(19.04)
|
27.8
(18.96)
|
| Title | Retinal Thickness |
|---|---|
| Description | Retinal images where sent to a reading center for analysis. Some images were not clear/distorted and could not be properly analyzed. This accounts for the discrepancy in the number of participants analyzed. |
| Time Frame | 36 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Sham Comparator | Fluocinolone Acetonide: 0.2 ug/Day Implant | Fluocinolone Acetonide: 0.5 ug/Day Implant |
|---|---|---|---|
| Arm/Group Description | Procedure: Standard of care laser photocoagulation | Dose 0.2 ug/day Medidur Implant | Dose 0.5 ug/day Medidur implant |
| Measure Participants | 182 | 369 | 388 |
| Mean (Standard Deviation) [microns] |
146.1
(192.10)
|
113.5
(151.46)
|
131.8
(162.46)
|
Adverse Events
| Time Frame | ||||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Three subjects were randomized but did not receive treatment. These subjects were not included in the safety analysis, which accounts for the discrepancy in the overall number of participants. | |||||
| Arm/Group Title | Sham Comparator | Fluocinolone Acetonide: 0.2 ug/Day Implant | Fluocinolone Acetonide: 0.5 ug/Day Implant | |||
| Arm/Group Description | Standard of care laser photocoagulation | Dose 0.2 ug/day Medidur implant | Dose 0.5 ug/day Medidur implant | |||
All Cause Mortality |
||||||
| Sham Comparator | Fluocinolone Acetonide: 0.2 ug/Day Implant | Fluocinolone Acetonide: 0.5 ug/Day Implant | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Sham Comparator | Fluocinolone Acetonide: 0.2 ug/Day Implant | Fluocinolone Acetonide: 0.5 ug/Day Implant | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 112/185 (60.5%) | 292/375 (77.9%) | 331/393 (84.2%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 1/185 (0.5%) | 1 | 3/375 (0.8%) | 4 | 3/393 (0.8%) | 3 |
| Coagulopathy | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Haemorrhagic anaemia | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Pancytopenia | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Cardiac disorders | ||||||
| Acute coronary syndrome | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Acute left ventricular failure | 0/185 (0%) | 0 | 1/375 (0.3%) | 2 | 0/393 (0%) | 0 |
| Acute myocardial infarction | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 1/393 (0.3%) | 1 |
| Angina pectoris | 2/185 (1.1%) | 2 | 5/375 (1.3%) | 9 | 6/393 (1.5%) | 6 |
| Angina unstable | 0/185 (0%) | 0 | 4/375 (1.1%) | 5 | 4/393 (1%) | 4 |
| Atrial fibrillation | 1/185 (0.5%) | 1 | 1/375 (0.3%) | 1 | 1/393 (0.3%) | 1 |
| Atrial flutter | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Atrial tachycardia | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Atrioventricular block | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 1/393 (0.3%) | 1 |
| Atrioventricular block complete | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Bradycardia | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 2/393 (0.5%) | 2 |
| Bundle branch block | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Bundle branch block left | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Cardiac arrest | 0/185 (0%) | 0 | 4/375 (1.1%) | 4 | 4/393 (1%) | 4 |
| Cardiac disorder | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 3/393 (0.8%) | 5 |
| Cardiac failure | 1/185 (0.5%) | 1 | 3/375 (0.8%) | 3 | 1/393 (0.3%) | 1 |
| Cardiac failure congestive | 8/185 (4.3%) | 8 | 12/375 (3.2%) | 17 | 16/393 (4.1%) | 25 |
| Cardiac fibrillation | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Cardiac valve disease | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Cardio-respiratory arrest | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Cardiomyopathy | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 2/393 (0.5%) | 3 |
| Cardiopulmonary failure | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Cardiovascular insufficiency | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Coronary artery disease | 4/185 (2.2%) | 5 | 10/375 (2.7%) | 13 | 15/393 (3.8%) | 15 |
| Coronary artery occlusion | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Ischaemic cardiomyopathy | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Left ventricular dysfunction | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Left ventricular failure | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Myocardial infarction | 5/185 (2.7%) | 5 | 14/375 (3.7%) | 17 | 16/393 (4.1%) | 17 |
| Myocardial ischaemia | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 1/393 (0.3%) | 1 |
| Nodal arrhythmia | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Pericardial effusion | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Pericarditis | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Right ventricular failure | 0/185 (0%) | 0 | 2/375 (0.5%) | 2 | 0/393 (0%) | 0 |
| Sick sinus syndrome | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Sinus arrhythmia | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Sinus bradycardia | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Congenital, familial and genetic disorders | ||||||
| Tracheo-oesophageal fistula | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Ear and labyrinth disorders | ||||||
| Vertigo | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 2/393 (0.5%) | 2 |
| Endocrine disorders | ||||||
| Hyperthyroidism | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Eye disorders | ||||||
| Amaurosis fugax | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Angle closure glaucoma | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 2/393 (0.5%) | 2 |
| Anterior capsule contraction | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Blindness | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Blindness | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Cataract | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Cataract subcapsular | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Conjunctival ulcer | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Corneal thinning | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Diabetic retinal oedema | 1/185 (0.5%) | 2 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Diabetic retinal oedema | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Diabetic retinopathy | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 1/393 (0.3%) | 1 |
| Diabetic retinopathy | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Eye haemorrhage | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Eye pain | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Glaucoma | 2/185 (1.1%) | 2 | 12/375 (3.2%) | 12 | 12/393 (3.1%) | 12 |
| Glaucoma | 1/185 (0.5%) | 1 | 1/375 (0.3%) | 1 | 3/393 (0.8%) | 3 |
| Hyphaema | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Hypotony of eye | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Iris adhesions | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Iris bombe | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Iris incarceration | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Keratitis | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Lens dislocation | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Lens dislocation | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Macular hole | 0/185 (0%) | 0 | 2/375 (0.5%) | 2 | 0/393 (0%) | 0 |
| Macular oedema | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Macular oedema | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Maculopathy | 2/185 (1.1%) | 5 | 2/375 (0.5%) | 2 | 2/393 (0.5%) | 2 |
| Maculopathy | 1/185 (0.5%) | 1 | 1/375 (0.3%) | 1 | 2/393 (0.5%) | 2 |
| Ocular hypertension | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 2/393 (0.5%) | 2 |
| Open angle glaucoma | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 2/393 (0.5%) | 2 |
| Optic ischaemic neuropathy | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Posterior capsule rupture | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Retinal artery embolism | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Retinal artery occlusion | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Retinal detachment | 3/185 (1.6%) | 4 | 2/375 (0.5%) | 2 | 4/393 (1%) | 4 |
| Retinal detachment | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 1/393 (0.3%) | 1 |
| Retinal tear | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Retinal tear | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Retinal vein occlusion | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Scleral thinning | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Uveitis | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Visual acuity reduced | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 2/393 (0.5%) | 2 |
| Visual impairment | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Vitreous haemorrhage | 6/185 (3.2%) | 8 | 10/375 (2.7%) | 13 | 8/393 (2%) | 9 |
| Vitreous haemorrhage | 8/185 (4.3%) | 9 | 5/375 (1.3%) | 6 | 9/393 (2.3%) | 10 |
| Vitritis | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Vitritis | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Abdominal pain | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 1/393 (0.3%) | 1 |
| Abdominal pain lower | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Ascites | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Diabetic gastroparesis | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 2/393 (0.5%) | 2 |
| Diarrhoea | 1/185 (0.5%) | 1 | 2/375 (0.5%) | 2 | 0/393 (0%) | 0 |
| Enteritis | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Enterocolitis | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Faecaloma | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Gastric ulcer | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Gastritis | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Gastrointestinal haemorrhage | 0/185 (0%) | 0 | 2/375 (0.5%) | 2 | 1/393 (0.3%) | 1 |
| Gastrointestinal ulcer | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Hiatus hernia | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Impaired gastric emptying | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Intestinal ischaemia | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 1/393 (0.3%) | 1 |
| Intra-abdominal haemorrhage | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Mesenteric artery embolism | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Pancreatitis | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 2/393 (0.5%) | 3 |
| Peritonitis | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Retroperitoneum cyst | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Stomatitis | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Upper gastrointestinal haemorrhage | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Vomiting | 1/185 (0.5%) | 1 | 3/375 (0.8%) | 3 | 0/393 (0%) | 0 |
| General disorders | ||||||
| Adverse drug reaction | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Chest pain | 3/185 (1.6%) | 3 | 8/375 (2.1%) | 9 | 4/393 (1%) | 4 |
| Cyst | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Death | 1/185 (0.5%) | 1 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Hernia | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Hernia obstructive | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Impaired healing | 0/185 (0%) | 0 | 2/375 (0.5%) | 2 | 1/393 (0.3%) | 1 |
| Multi-organ failure | 1/185 (0.5%) | 1 | 1/375 (0.3%) | 1 | 1/393 (0.3%) | 1 |
| Non-cardiac chest pain | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Oedema | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 2/393 (0.5%) | 2 |
| Oedema peripheral | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Polyp | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Pyrexia | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Sudden cardiac death | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Hepatobiliary disorders | ||||||
| Cholecystitis | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Cholelithiasis | 1/185 (0.5%) | 1 | 2/375 (0.5%) | 2 | 1/393 (0.3%) | 1 |
| Hepatic steatosis | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Infections and infestations | ||||||
| Abscess | 2/185 (1.1%) | 2 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Abscess limb | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Appendicitis | 1/185 (0.5%) | 1 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Appendicitis perforated | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Arteriovenous graft site infection | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Arthritis bacterial | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 3/393 (0.8%) | 3 |
| Blister infected | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Bronchitis | 0/185 (0%) | 0 | 2/375 (0.5%) | 3 | 1/393 (0.3%) | 1 |
| Catheter site infection | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Cellulitis | 4/185 (2.2%) | 4 | 4/375 (1.1%) | 6 | 6/393 (1.5%) | 7 |
| Cellulitis staphylococcal | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Clostridium difficile colitis | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Cystitis | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Diabetic foot infection | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Diverticulitis | 1/185 (0.5%) | 1 | 1/375 (0.3%) | 1 | 1/393 (0.3%) | 1 |
| Encephalitis viral | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Endocarditis | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Endophthalmitis | 0/185 (0%) | 0 | 2/375 (0.5%) | 2 | 0/393 (0%) | 0 |
| Endophthalmitis | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Enterocolitis infectious | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Eye infection fungal | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Gangrene | 1/185 (0.5%) | 1 | 1/375 (0.3%) | 1 | 6/393 (1.5%) | 7 |
| Gastroenteritis | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 2/393 (0.5%) | 2 |
| Gastroenteritis viral | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Hepatitis C | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Herpes zoster | 0/185 (0%) | 0 | 2/375 (0.5%) | 2 | 0/393 (0%) | 0 |
| Infection | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 2/393 (0.5%) | 2 |
| Kidney infection | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 1/393 (0.3%) | 1 |
| Liver abscess | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Lobar pneumonia | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Localised infection | 1/185 (0.5%) | 1 | 3/375 (0.8%) | 3 | 3/393 (0.8%) | 3 |
| Lower respiratory tract infection | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Lung infection | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Lyme disease | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Necrotising fasciitis | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Osteomyelitis | 3/185 (1.6%) | 4 | 5/375 (1.3%) | 7 | 0/393 (0%) | 0 |
| Pneumonia | 4/185 (2.2%) | 4 | 13/375 (3.5%) | 13 | 10/393 (2.5%) | 12 |
| Pneumonia klebsiella | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Pneumonia legionella | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Pneumonia staphylococcal | 0/185 (0%) | 0 | 1/375 (0.3%) | 2 | 0/393 (0%) | 0 |
| Post procedural infection | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Postoperative wound infection | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Prostate infection | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 2 |
| Pulmonary tuberculosis | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Pyelonephritis | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Respiratory tract infection | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Sepsis | 0/185 (0%) | 0 | 2/375 (0.5%) | 2 | 5/393 (1.3%) | 5 |
| Sepsis syndrome | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Sinusitis | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Staphylococcal bacteraemia | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Staphylococcal infection | 1/185 (0.5%) | 1 | 2/375 (0.5%) | 2 | 1/393 (0.3%) | 1 |
| Staphylococcal sepsis | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Subcutaneous abscess | 0/185 (0%) | 0 | 2/375 (0.5%) | 2 | 0/393 (0%) | 0 |
| Tracheostomy infection | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Urinary tract infection | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 2/393 (0.5%) | 2 |
| Urosepsis | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Wound infection | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 2 |
| Wound infection staphylococcal | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 3/393 (0.8%) | 3 |
| Injury, poisoning and procedural complications | ||||||
| Ankle fracture | 2/185 (1.1%) | 2 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Cataract operation complication | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Cataract operation complication | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Chemical eye injury | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Eye operation complication | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Fall | 1/185 (0.5%) | 1 | 2/375 (0.5%) | 2 | 3/393 (0.8%) | 3 |
| Femoral neck fracture | 2/185 (1.1%) | 2 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Femur fracture | 0/185 (0%) | 0 | 2/375 (0.5%) | 2 | 2/393 (0.5%) | 2 |
| Forearm fracture | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Foreign body trauma | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Head injury | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Hip fracture | 3/185 (1.6%) | 3 | 2/375 (0.5%) | 2 | 4/393 (1%) | 4 |
| Humerus fracture | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Limb injury | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Lower limb fracture | 1/185 (0.5%) | 1 | 1/375 (0.3%) | 1 | 1/393 (0.3%) | 1 |
| Lumbar vertebral fracture | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Pelvic fracture | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 2/393 (0.5%) | 2 |
| Post concussion syndrome | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Respiratory fume inhalation disorder | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Road traffic accident | 0/185 (0%) | 0 | 2/375 (0.5%) | 2 | 0/393 (0%) | 0 |
| Skin laceration | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Spinal compression fracture | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Splenic injury | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Tendon rupture | 2/185 (1.1%) | 2 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Tibia fracture | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Traumatic shock | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Ulna fracture | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Upper limb fracture | 1/185 (0.5%) | 1 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Wound dehiscence | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Wound haemorrhage | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Investigations | ||||||
| Blood glucose decreased | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Blood glucose increased | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Catheterisation cardiac | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 4/393 (1%) | 4 |
| Diagnostic procedure | 0/185 (0%) | 0 | 1/375 (0.3%) | 2 | 0/393 (0%) | 0 |
| Full blood count decreased | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 2 |
| Heart rate decreased | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Hysteroscopy | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| International normalised ratio increased | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Intraocular pressure increased | 0/185 (0%) | 0 | 12/375 (3.2%) | 16 | 20/393 (5.1%) | 22 |
| Intraocular pressure increased | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 2/393 (0.5%) | 2 |
| Oxygen saturation decreased | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Metabolism and nutrition disorders | ||||||
| Dehydration | 2/185 (1.1%) | 2 | 3/375 (0.8%) | 3 | 2/393 (0.5%) | 2 |
| Diabetes mellitus | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 2/393 (0.5%) | 2 |
| Diabetes mellitus inadequate control | 1/185 (0.5%) | 3 | 2/375 (0.5%) | 2 | 3/393 (0.8%) | 3 |
| Diabetic foot | 0/185 (0%) | 0 | 2/375 (0.5%) | 2 | 0/393 (0%) | 0 |
| Diabetic ketoacidosis | 0/185 (0%) | 0 | 2/375 (0.5%) | 2 | 1/393 (0.3%) | 1 |
| Electrolyte imbalance | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Fluid overload | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 1/393 (0.3%) | 1 |
| Fluid retention | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Gout | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Hyperglycaemia | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 2/393 (0.5%) | 2 |
| Hyperkalaemia | 1/185 (0.5%) | 1 | 3/375 (0.8%) | 3 | 1/393 (0.3%) | 1 |
| Hypoglycaemia | 4/185 (2.2%) | 4 | 4/375 (1.1%) | 4 | 4/393 (1%) | 4 |
| Hypokalaemia | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Hyponatraemia | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Shock hypoglycaemic | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Arthritis | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Arthropathy | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Back pain | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 1/393 (0.3%) | 1 |
| Bone pain | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Flank pain | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Intervertebral disc protrusion | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Muscular weakness | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 3/393 (0.8%) | 3 |
| Musculoskeletal pain | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Neuropathic arthropathy | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Osteoarthritis | 0/185 (0%) | 0 | 2/375 (0.5%) | 2 | 0/393 (0%) | 0 |
| Pain in extremity | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 1/393 (0.3%) | 1 |
| Polymyalgia rheumatica | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 2 |
| Rheumatoid nodule | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Spinal column stenosis | 0/185 (0%) | 0 | 3/375 (0.8%) | 3 | 0/393 (0%) | 0 |
| Spinal osteoarthritis | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Spondylitis | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Spondylolisthesis | 0/185 (0%) | 0 | 2/375 (0.5%) | 2 | 0/393 (0%) | 0 |
| Synovitis | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Adenocarcinoma | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Adenoma benign | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Bone neoplasm malignant | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Brain neoplasm | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Breast cancer female | 0/185 (0%) | 0 | 2/375 (0.5%) | 2 | 0/393 (0%) | 0 |
| Colon cancer | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 1/393 (0.3%) | 1 |
| Colon cancer stage II | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Colorectal cancer metastatic | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Endometrial cancer | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Gastric cancer | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Gastrooesophageal cancer | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Hepatic neoplasm malignant | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Lung neoplasm malignant | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Metastatic carcinoma of the bladder | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Multiple myeloma | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Oesophageal neoplasm | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Ovarian cancer | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Pancreatic carcinoma | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Prostate cancer | 0/185 (0%) | 0 | 2/375 (0.5%) | 2 | 1/393 (0.3%) | 1 |
| Salivary gland neoplasm | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Small cell carcinoma | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Thyroid neoplasm | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Uterine cancer | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Nervous system disorders | ||||||
| Brain stem infarction | 1/185 (0.5%) | 1 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Carotid artery disease | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Carotid artery occlusion | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Carotid artery stenosis | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 1/393 (0.3%) | 1 |
| Cerebral haemorrhage | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Cerebrovascular accident | 6/185 (3.2%) | 6 | 9/375 (2.4%) | 12 | 10/393 (2.5%) | 10 |
| Convulsion | 2/185 (1.1%) | 2 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Dementia | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Diabetic autonomic neuropathy | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Diabetic coma | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Dizziness | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Embolic cerebral infarction | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Haemorrhage intracranial | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Hemiparesis | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 2/393 (0.5%) | 2 |
| Hypertensive encephalopathy | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Ischaemic stroke | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Lacunar infarction | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 1/393 (0.3%) | 1 |
| Loss of consciousness | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 1/393 (0.3%) | 1 |
| Myelopathy | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Neurological symptom | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Spinal cord disorder | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Syncope | 0/185 (0%) | 0 | 3/375 (0.8%) | 3 | 4/393 (1%) | 5 |
| Thalamic infarction | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Transient ischaemic attack | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 5/393 (1.3%) | 5 |
| Vascular dementia | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Psychiatric disorders | ||||||
| Completed suicide | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Suicidal ideation | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Renal and urinary disorders | ||||||
| Calculus ureteric | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Nephrolithiasis | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 2/393 (0.5%) | 2 |
| Proteinuria | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Renal disorder | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Renal failure | 3/185 (1.6%) | 3 | 11/375 (2.9%) | 13 | 10/393 (2.5%) | 10 |
| Renal failure acute | 0/185 (0%) | 0 | 3/375 (0.8%) | 6 | 3/393 (0.8%) | 3 |
| Renal failure chronic | 1/185 (0.5%) | 2 | 4/375 (1.1%) | 5 | 3/393 (0.8%) | 3 |
| Urinary retention | 0/185 (0%) | 0 | 2/375 (0.5%) | 2 | 0/393 (0%) | 0 |
| Reproductive system and breast disorders | ||||||
| Benign prostatic hyperplasia | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Asthma | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Chronic obstructive pulmonary disease | 1/185 (0.5%) | 1 | 4/375 (1.1%) | 6 | 0/393 (0%) | 0 |
| Dyspnoea | 1/185 (0.5%) | 1 | 3/375 (0.8%) | 3 | 4/393 (1%) | 4 |
| Epistaxis | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Hypoxia | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Pleural effusion | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 1/393 (0.3%) | 1 |
| Pleurisy | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Pneumonia aspiration | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Respiratory failure | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 3/393 (0.8%) | 3 |
| Vocal cord thickening | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||
| Decubitus ulcer | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Diabetic ulcer | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Neuropathic ulcer | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Skin ulcer | 0/185 (0%) | 0 | 3/375 (0.8%) | 3 | 0/393 (0%) | 0 |
| Urticaria | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Surgical and medical procedures | ||||||
| Amputation revision | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Angioplasty | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Ankle operation | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Arterial stent insertion | 0/185 (0%) | 0 | 2/375 (0.5%) | 4 | 0/393 (0%) | 0 |
| Arteriovenous graft | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Bladder operation | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Blepharoplasty | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Blepharoplasty | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Cardiac pacemaker insertion | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 1/393 (0.3%) | 1 |
| Carotid artery stent insertion | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Cataract operation | 33/185 (17.8%) | 33 | 188/375 (50.1%) | 188 | 231/393 (58.8%) | 231 |
| Cataract operation | 32/185 (17.3%) | 32 | 85/375 (22.7%) | 85 | 87/393 (22.1%) | 87 |
| Cholecystectomy | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Colon operation | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Coronary arterial stent insertion | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Coronary artery bypass | 1/185 (0.5%) | 1 | 1/375 (0.3%) | 1 | 2/393 (0.5%) | 2 |
| Cryotherapy | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Dialysis device insertion | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Dupuytren's contracture operation | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Eye excision | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Eye operation | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Foot operation | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Gallbladder operation | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Glaucoma surgery | 1/185 (0.5%) | 1 | 7/375 (1.9%) | 7 | 8/393 (2%) | 10 |
| Glaucoma surgery | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 5/393 (1.3%) | 5 |
| Haemorrhoid operation | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Hernia repair | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Hip arthroplasty | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 3/393 (0.8%) | 3 |
| Hysterectomy | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 2/393 (0.5%) | 2 |
| Inguinal hernia repair | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Intraocular lens extraction | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Intraocular lens implant | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 2/393 (0.5%) | 2 |
| Iridotomy | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Knee arthroplasty | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 1/393 (0.3%) | 1 |
| Leg amputation | 1/185 (0.5%) | 1 | 1/375 (0.3%) | 1 | 1/393 (0.3%) | 1 |
| Pancreas transplant | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Penile prosthesis insertion | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Percutaneous coronary intervention | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Ptosis repair | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Removal of foreign body | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Removal of foreign body from eye | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Renal transplant | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Retinal operation | 1/185 (0.5%) | 1 | 1/375 (0.3%) | 1 | 2/393 (0.5%) | 2 |
| Retinal operation | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 1/393 (0.3%) | 1 |
| Rotator cuff repair | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Shoulder arthroplasty | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Sinus operation | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Stent placement | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Thyroidectomy | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Toe amputation | 0/185 (0%) | 0 | 4/375 (1.1%) | 4 | 2/393 (0.5%) | 2 |
| Trabeculectomy | 0/185 (0%) | 0 | 10/375 (2.7%) | 10 | 22/393 (5.6%) | 22 |
| Trabeculoplasty | 0/185 (0%) | 0 | 3/375 (0.8%) | 5 | 10/393 (2.5%) | 11 |
| Transurethral prostatectomy | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 2/393 (0.5%) | 2 |
| Tumour excision | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Umbilical hernia repair | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Uterine polypectomy | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Vascular cauterisation | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Vitrectomy | 16/185 (8.6%) | 16 | 19/375 (5.1%) | 21 | 23/393 (5.9%) | 30 |
| Vitrectomy | 13/185 (7%) | 13 | 25/375 (6.7%) | 27 | 27/393 (6.9%) | 29 |
| Wound closure | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Vascular disorders | ||||||
| Aortic stenosis | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Arteriosclerosis | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Arteritis | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Blood pressure fluctuation | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Deep vein thrombosis | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Femoral artery occlusion | 0/185 (0%) | 0 | 0/375 (0%) | 0 | 1/393 (0.3%) | 1 |
| Haemorrhage | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Hypertension | 2/185 (1.1%) | 2 | 3/375 (0.8%) | 5 | 2/393 (0.5%) | 2 |
| Hypertensive crisis | 1/185 (0.5%) | 1 | 1/375 (0.3%) | 1 | 1/393 (0.3%) | 1 |
| Hypotension | 0/185 (0%) | 0 | 3/375 (0.8%) | 3 | 1/393 (0.3%) | 1 |
| Ischaemia | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Lymphoedema | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Malignant hypertension | 1/185 (0.5%) | 1 | 0/375 (0%) | 0 | 0/393 (0%) | 0 |
| Orthostatic hypotension | 0/185 (0%) | 0 | 1/375 (0.3%) | 1 | 0/393 (0%) | 0 |
| Peripheral ischaemia | 0/185 (0%) | 0 | 1/375 (0.3%) | 2 | 0/393 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||
| Sham Comparator | Fluocinolone Acetonide: 0.2 ug/Day Implant | Fluocinolone Acetonide: 0.5 ug/Day Implant | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 174/185 (94.1%) | 360/375 (96%) | 388/393 (98.7%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 9/185 (4.9%) | 9 | 33/375 (8.8%) | 36 | 42/393 (10.7%) | 46 |
| Eye disorders | ||||||
| Cataract | 53/185 (28.6%) | 54 | 171/375 (45.6%) | 183 | 213/393 (54.2%) | 234 |
| Cataract | 46/185 (24.9%) | 47 | 109/375 (29.1%) | 115 | 121/393 (30.8%) | 127 |
| Cataract subcapsular | 8/185 (4.3%) | 9 | 28/375 (7.5%) | 34 | 24/393 (6.1%) | 34 |
| Conjunctival haemorrhage | 20/185 (10.8%) | 21 | 43/375 (11.5%) | 50 | 50/393 (12.7%) | 62 |
| Dry eye | 11/185 (5.9%) | 11 | 23/375 (6.1%) | 24 | 22/393 (5.6%) | 24 |
| Dry eye | 9/185 (4.9%) | 9 | 23/375 (6.1%) | 24 | 17/393 (4.3%) | 18 |
| Eye irritation | 9/185 (4.9%) | 11 | 27/375 (7.2%) | 30 | 22/393 (5.6%) | 22 |
| Eye pain | 22/185 (11.9%) | 25 | 51/375 (13.6%) | 57 | 65/393 (16.5%) | 77 |
| Eye pain | 11/185 (5.9%) | 11 | 17/375 (4.5%) | 19 | 11/393 (2.8%) | 11 |
| Maculopathy | 16/185 (8.6%) | 21 | 22/375 (5.9%) | 24 | 33/393 (8.4%) | 36 |
| Maculopathy | 9/185 (4.9%) | 9 | 16/375 (4.3%) | 16 | 22/393 (5.6%) | 25 |
| Myodesopsia | 13/185 (7%) | 17 | 67/375 (17.9%) | 80 | 68/393 (17.3%) | 79 |
| Myodesopsia | 11/185 (5.9%) | 12 | 17/375 (4.5%) | 19 | 18/393 (4.6%) | 19 |
| Posterior capsule opacification | 6/185 (3.2%) | 6 | 32/375 (8.5%) | 35 | 25/393 (6.4%) | 27 |
| Posterior capsule opacification | 4/185 (2.2%) | 4 | 19/375 (5.1%) | 21 | 20/393 (5.1%) | 20 |
| Retinal haemorrhage | 11/185 (5.9%) | 13 | 9/375 (2.4%) | 10 | 17/393 (4.3%) | 18 |
| Vision blurred | 13/185 (7%) | 16 | 28/375 (7.5%) | 31 | 20/393 (5.1%) | 22 |
| Vision blurred | 4/185 (2.2%) | 5 | 21/375 (5.6%) | 24 | 14/393 (3.6%) | 15 |
| Visual acuity reduced | 17/185 (9.2%) | 22 | 39/375 (10.4%) | 44 | 35/393 (8.9%) | 42 |
| Visual acuity reduced | 14/185 (7.6%) | 19 | 25/375 (6.7%) | 27 | 23/393 (5.9%) | 35 |
| Visual impairment | 7/185 (3.8%) | 8 | 13/375 (3.5%) | 13 | 31/393 (7.9%) | 35 |
| Vitreous detachment | 12/185 (6.5%) | 12 | 26/375 (6.9%) | 26 | 20/393 (5.1%) | 20 |
| Vitreous haemorrhage | 25/185 (13.5%) | 33 | 38/375 (10.1%) | 52 | 46/393 (11.7%) | 62 |
| Vitreous haemorrhage | 22/185 (11.9%) | 32 | 36/375 (9.6%) | 53 | 49/393 (12.5%) | 65 |
| Gastrointestinal disorders | ||||||
| Constipation | 7/185 (3.8%) | 7 | 18/375 (4.8%) | 20 | 27/393 (6.9%) | 29 |
| Gastrooesophageal reflux disease | 11/185 (5.9%) | 13 | 22/375 (5.9%) | 22 | 26/393 (6.6%) | 26 |
| Nausea | 18/185 (9.7%) | 21 | 28/375 (7.5%) | 37 | 30/393 (7.6%) | 32 |
| Vomiting | 13/185 (7%) | 14 | 15/375 (4%) | 16 | 9/393 (2.3%) | 11 |
| Infections and infestations | ||||||
| Nasopharyngitis | 12/185 (6.5%) | 17 | 22/375 (5.9%) | 22 | 24/393 (6.1%) | 26 |
| Sinusitis | 7/185 (3.8%) | 10 | 16/375 (4.3%) | 17 | 22/393 (5.6%) | 27 |
| Upper respiratory tract infection | 9/185 (4.9%) | 10 | 9/375 (2.4%) | 10 | 20/393 (5.1%) | 26 |
| Urinary tract infection | 11/185 (5.9%) | 14 | 20/375 (5.3%) | 24 | 22/393 (5.6%) | 26 |
| Investigations | ||||||
| Intraocular pressure increased | 21/185 (11.4%) | 22 | 129/375 (34.4%) | 176 | 169/393 (43%) | 244 |
| Intraocular pressure increased | 22/185 (11.9%) | 22 | 40/375 (10.7%) | 48 | 50/393 (12.7%) | 67 |
| Metabolism and nutrition disorders | ||||||
| Hypercholesterolaemia | 13/185 (7%) | 13 | 24/375 (6.4%) | 24 | 24/393 (6.1%) | 24 |
| Nervous system disorders | ||||||
| Headache | 10/185 (5.4%) | 11 | 31/375 (8.3%) | 33 | 21/393 (5.3%) | 25 |
| Psychiatric disorders | ||||||
| Depression | 7/185 (3.8%) | 8 | 11/375 (2.9%) | 12 | 22/393 (5.6%) | 23 |
| Renal and urinary disorders | ||||||
| Renal failure | 7/185 (3.8%) | 7 | 19/375 (5.1%) | 19 | 25/393 (6.4%) | 28 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 7/185 (3.8%) | 10 | 17/375 (4.5%) | 17 | 21/393 (5.3%) | 26 |
| Vascular disorders | ||||||
| Hypertension | 29/185 (15.7%) | 33 | 43/375 (11.5%) | 50 | 57/393 (14.5%) | 61 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Kathleen Billman, Senior Director of Scientific Affairs |
|---|---|
| Organization | Alimera Sciences, Inc. |
| Phone | 678-572-1302 |
| kathleen.billman@alimerasciences.com |
Responsible Party:
Alimera Sciences
ClinicalTrials.gov Identifier:
NCT00344968
Other Study ID Numbers:
- C-01-05-001
First Posted:
Jun 27, 2006
Last Update Posted:
May 7, 2014
Last Verified:
Apr 1, 2014