ECLIPSE: An Open-label Extended Clinical Protocol of Ranibizumab to Evaluate Safety and Efficacy in Rare VEGF Driven Ocular Diseases.
Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01908816
Collaborator
(none)
270
39
1
27.4
6.9
0.3
Study Details
Study Description
Brief Summary
The pupose of this study is to evaluate the safety and the efficacy of ranibizumab in rare VEGF driven ocular diseases.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
270 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-label Extended Clinical Protocol of Ranibizumab to Evaluate Safety and Efficacy in Rare VEGF Driven Ocular Diseases.
Actual Study Start Date
:
Sep 26, 2013
Actual Primary Completion Date
:
Jan 8, 2016
Actual Study Completion Date
:
Jan 8, 2016
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ranibizumab 0.5 mg ranibizumab applied in an individualized regimen as IVT injection of 0.05 mL. |
Drug: ranibizumab
One injection of Ranibizumab 0.5 mg and retreatment according to disease activity and/or visual impairment on an as needed regimen (PRN)
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Adverse Events as a Measure of Safety and Tolerability [24 months]
Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs) for ocular and non-ocular events. Due to early termination, only descriptive analysis was conducted.
Secondary Outcome Measures
- Change From Baseline Best Corrected Visual Acuity (BCVA) for Patients With Choroidal Neovascularization (CNV) and Macular Edema (ME) [3 months, 12 months]
BCVA change for diseases affecting the macular area either through CNV or ME. BCVA is tested using the ETDRS (Early Treatment Diabetic Retinopathy Study), the Snellen or Monoyer scales. The three scales are designed to measure visual acuity. ETDRS score is expressed in letter, Snellen and Monoyer score in fraction. BCVA assessment is presented in ETDRS after conversion if collected in Snellen or Monoyer. (Monoyer converted to Snellen = 2 x (Monoyer fraction) and Snellen converted to approximate ETDRS letters = 1x log(Snellen fraction). ETDRS letter score was transformed in logMAR unit for statistical analysis (- LogMAR = -(ETDRS-85)/50). The worse ETDRS letter score is 0 (logMAR 2.3) and the best ETDRS letter score is 100 (logMAR -0.3).
- Average Change of Neovascularization Extension for Patients With Neovascular Glaucoma [3 month, 12 month]
The extent of iris neovascularization was assessed by iris photography and graded using the "Teich and Walsh grading system". This grading system measures the number of quadrant at iris pupillary zone or iris ciliary zone where iris neovascularization (NV) is observed. Grade 0 = "No iris vascularization", Grade 1= Less than 2 quadrants of NV at iris pupillary zone, Grade 2 = More than 2 quadrants of NV at iris pupillary zone, Grade 3 =Grade 2 + less than 3 quadrants of NV at iris ciliary zone and/or ectropion uveae; Grade 4 =More than 3 quadrants of NV at iris ciliary zone and/or ectropion uveae)
- Proportion of Patient With Vitreous Cavity Hemorrhage Occurrence for Patient With Proliferative Retinopathy [3 months, 12 month]
Occurrence of postoperative vitreous cavity hemorrhage
- Mean Change From Baseline in Change in Central Retinal Thickness for Patients With CNV (Choroidal Neovascularization) and ME (Macular Edema)" [3 months, 12 month]
CRT in micrometers assessed by Optical Tomography (OCT) at each single study visit. A reduction is thickness indicates an improvement is the lesion area
- Proportion of Patients With Angiographic Leakage [3 months, 12 month]
Angiography was taken via fluorescein angiography. Any increases of angiographic leakage was counted between baseline and month 3. Also any decreases of angiographic leakage was counted between baseline and 3 month.
- Ranibizumab Injection [3 months, 12 month]
Number of ranibizumab injections needed by decreased visual acuity and/or increasing retinal thickness in 3 months of observation period
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Active choroidal neovascularization (CNV)
-
Active macular edema (ME)
-
Rubeosis iridis/neovascular glaucoma.
-
Proliferative diabetic retinopathy requiring vitrectomy.
Exclusion Criteria:
-
wet Age-related macular degeneration
-
pathologic myopia
-
pseudoxanthoma elasticum
-
diabetic macular edema
-
retinal vein occlusion
-
< 18 years of age
-
History of hypersensitivity to ranibizumab
-
Use of any systemic anti-angiogenic drugs 3 months before inclusion
-
Women of child-bearing potential and Pregnant or nursing (lactating) women.
-
Active or suspected ocular infection
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis Investigative Site | Bobigny cedex | Seine Saint Denis | France | 93009 |
| 2 | Novartis Investigative Site | Amiens Cedex 1 | France | 80054 | |
| 3 | Novartis Investigative Site | Angers | France | 49044 | |
| 4 | Novartis Investigative Site | Bordeaux | France | 33000 | |
| 5 | Novartis Investigative Site | Bordeaux | France | 33100 | |
| 6 | Novartis Investigative Site | Caen | France | 14050 | |
| 7 | Novartis Investigative Site | Creteil | France | 94000 | |
| 8 | Novartis Investigative Site | Ecully | France | 69130 | |
| 9 | Novartis Investigative Site | Grenoble | France | 38000 | |
| 10 | Novartis Investigative Site | Grenoble | France | 38043 | |
| 11 | Novartis Investigative Site | Lille | France | 59000 | |
| 12 | Novartis Investigative Site | Lyon Cedex 04 | France | 69317 | |
| 13 | Novartis Investigative Site | Lyon | France | 69275 | |
| 14 | Novartis Investigative Site | Mantes la jolie | France | 78201 | |
| 15 | Novartis Investigative Site | Marseille Cedex 8 | France | 13008 | |
| 16 | Novartis Investigative Site | Marseille | France | F 13008 | |
| 17 | Novartis Investigative Site | Melun | France | 77000 | |
| 18 | Novartis Investigative Site | Montauban | France | 82000 | |
| 19 | Novartis Investigative Site | Montpellier | France | 34000 | |
| 20 | Novartis Investigative Site | Mulhouse cedex | France | 68070 | |
| 21 | Novartis Investigative Site | Nantes Cedex 1 | France | 44093 | |
| 22 | Novartis Investigative Site | Nice | France | 06000 | |
| 23 | Novartis Investigative Site | Paris cedex 10 | France | 75010 | |
| 24 | Novartis Investigative Site | Paris Cedex 19 | France | 75940 | |
| 25 | Novartis Investigative Site | Paris, Cedex 12 | France | F-75571 | |
| 26 | Novartis Investigative Site | Paris | France | 75006 | |
| 27 | Novartis Investigative Site | Paris | France | 75013 | |
| 28 | Novartis Investigative Site | Paris | France | 75014 | |
| 29 | Novartis Investigative Site | Paris | France | 75015 | |
| 30 | Novartis Investigative Site | Poitiers | France | 86021 | |
| 31 | Novartis Investigative Site | Rouen | France | 76100 | |
| 32 | Novartis Investigative Site | Saint-Jean | France | 31240 | |
| 33 | Novartis Investigative Site | Saitnt Herblain | France | 44819 | |
| 34 | Novartis Investigative Site | St-Priest-en-Jarez | France | 42270 | |
| 35 | Novartis Investigative Site | Strasbourg Cedex | France | 67091 | |
| 36 | Novartis Investigative Site | Toulouse | France | 31077 | |
| 37 | Novartis Investigative Site | Tours | France | 37000 | |
| 38 | Novartis Investigative Site | Tours | France | 37044 | |
| 39 | Novartis Investigative Site | Vannes | France | 56000 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01908816
Other Study ID Numbers:
- CRFB002GFR02
First Posted:
Jul 26, 2013
Last Update Posted:
Aug 12, 2019
Last Verified:
Jul 1, 2019
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | open-label, single arm study evaluating the safety of 0.5 mg ranibizumab. Patients received individualized ranibizumab intravitreal injections based on evidence of disease activity. The study was early terminated due to low recruitment that hampered to address the primary endpoint of the study |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | CNV (Choroidal Neovascularization) | ME (Macular Edema) | RI/NVG (Rubeosis Iridis and Neovacular Glaucoma) | PDR/V |
|---|---|---|---|---|
| Arm/Group Description | All patients received 0.5 mg ranibizumab IVT injection | All patients received 0.5 mg ranibizumab IVT injection | All patients received 0.5 mg ranibizumab IVT injection | (Proliferative Diabetic Retinopathy requiring Vitrectomy). All patients received 0.5 mg ranibizumab IVT injection |
| Period Title: Overall Study | ||||
| STARTED | 93 | 84 | 58 | 35 |
| COMPLETED | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 93 | 84 | 58 | 35 |
Baseline Characteristics
| Arm/Group Title | CNV (Choroidal Neovascularization) | ME (Macular Edema) | RI/NVG (Rubeosis Iridis and Neovacular Glaucoma) | PDR/V | Total |
|---|---|---|---|---|---|
| Arm/Group Description | All patients received 0.5 mg ranibizumab IVT injection | All patients received 0.5 mg ranibizumab IVT injection | All patients received 0.5 mg ranibizumab IVT injection | (Proliferative Diabetic Retinopathy requiring Vitrectomy). All patients received 0.5 mg ranibizumab IVT injection | Total of all reporting groups |
| Overall Participants | 93 | 84 | 56 | 34 | 267 |
| Age (Years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [Years] |
49.7
(16.85)
|
64.5
(13.99)
|
70.9
(13.02)
|
56.5
(9.86)
|
59.7
(16.62)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
48
51.6%
|
35
41.7%
|
26
46.4%
|
17
50%
|
126
47.2%
|
| Male |
45
48.4%
|
49
58.3%
|
30
53.6%
|
17
50%
|
141
52.8%
|
Outcome Measures
| Title | Number of Participants With Adverse Events as a Measure of Safety and Tolerability |
|---|---|
| Description | Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs) for ocular and non-ocular events. Due to early termination, only descriptive analysis was conducted. |
| Time Frame | 24 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population: all patients who received at least one application of study treatment and had at least one post-baseline safety assessment. The statement that a patient had no adverse events also constituted a safety assessment. All safety evaluations were carried out on the safety population. |
| Arm/Group Title | CNV (Choroidal Neovascularization) | ME (Macular Edema) | RI/NVG (Rubeosis Iridis and Neovacular Glaucoma) | PDR/V |
|---|---|---|---|---|
| Arm/Group Description | All patients received 0.5 mg ranibizumab IVT injection | All patients received 0.5 mg ranibizumab IVT injection | All patients received 0.5 mg ranibizumab IVT injection | (Proliferative Diabetic Retinopathy requiring Vitrectomy). All patients received 0.5 mg ranibizumab IVT injection |
| Measure Participants | 93 | 84 | 58 | 35 |
| Non- serious adverse events |
2
2.2%
|
21
25%
|
1
1.8%
|
0
0%
|
| Serious adverse events |
11
11.8%
|
15
17.9%
|
31
55.4%
|
14
41.2%
|
| Death |
1
1.1%
|
0
0%
|
7
12.5%
|
1
2.9%
|
| Title | Change From Baseline Best Corrected Visual Acuity (BCVA) for Patients With Choroidal Neovascularization (CNV) and Macular Edema (ME) |
|---|---|
| Description | BCVA change for diseases affecting the macular area either through CNV or ME. BCVA is tested using the ETDRS (Early Treatment Diabetic Retinopathy Study), the Snellen or Monoyer scales. The three scales are designed to measure visual acuity. ETDRS score is expressed in letter, Snellen and Monoyer score in fraction. BCVA assessment is presented in ETDRS after conversion if collected in Snellen or Monoyer. (Monoyer converted to Snellen = 2 x (Monoyer fraction) and Snellen converted to approximate ETDRS letters = 1x log(Snellen fraction). ETDRS letter score was transformed in logMAR unit for statistical analysis (- LogMAR = -(ETDRS-85)/50). The worse ETDRS letter score is 0 (logMAR 2.3) and the best ETDRS letter score is 100 (logMAR -0.3). |
| Time Frame | 3 months, 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population (ITT): all patients who received at least one application of study treatment and had at least one post-baseline efficacy assessment. The ITT population was the main analysis set for efficacy evaluations |
| Arm/Group Title | CNV (Choroidal Neovascularization) | ME (Macular Edema) |
|---|---|---|
| Arm/Group Description | All patients received 0.5 mg ranibizumab IVT injection | All patients received 0.5 mg ranibizumab IVT injection |
| Measure Participants | 93 | 84 |
| 3 Month |
7.3
(14.47)
|
4.5
(11.61)
|
| 12 Month |
5.7
(12.08)
|
5.2
(16.46)
|
| Title | Average Change of Neovascularization Extension for Patients With Neovascular Glaucoma |
|---|---|
| Description | The extent of iris neovascularization was assessed by iris photography and graded using the "Teich and Walsh grading system". This grading system measures the number of quadrant at iris pupillary zone or iris ciliary zone where iris neovascularization (NV) is observed. Grade 0 = "No iris vascularization", Grade 1= Less than 2 quadrants of NV at iris pupillary zone, Grade 2 = More than 2 quadrants of NV at iris pupillary zone, Grade 3 =Grade 2 + less than 3 quadrants of NV at iris ciliary zone and/or ectropion uveae; Grade 4 =More than 3 quadrants of NV at iris ciliary zone and/or ectropion uveae) |
| Time Frame | 3 month, 12 month |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population (ITT): all patients who received at least one application of study treatment and had at least one post-baseline efficacy assessment. The ITT population was the main analysis set for efficacy evaluations |
| Arm/Group Title | Ranibizumab 0.5 mg |
|---|---|
| Arm/Group Description | All patients received 0.5 mg ranibizumab IVT injection |
| Measure Participants | 56 |
| 3 Month,Grade 0 |
12
|
| 3 Month, Grade 1 |
6
|
| 3 Month, Grade 2 |
8
|
| 3 Month, Grade 3 |
3
|
| 3 Month, Grade 4 |
2
|
| 12 Month, Grade 0 |
11
|
| 12 Month, Grade 1 |
4
|
| 12 Month, Grade 2 |
2
|
| 12 Month, Grade 3 |
4
|
| 12 Month, Grade 4 |
4
|
| Title | Proportion of Patient With Vitreous Cavity Hemorrhage Occurrence for Patient With Proliferative Retinopathy |
|---|---|
| Description | Occurrence of postoperative vitreous cavity hemorrhage |
| Time Frame | 3 months, 12 month |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population (ITT): all patients who received at least one application of study treatment and had at least one post-baseline efficacy assessment. The ITT population was the main analysis set for efficacy evaluations. (n) is the number of participants with an observed value |
| Arm/Group Title | PDR/V |
|---|---|
| Arm/Group Description | (Proliferative Diabetic Retinopathy requiring Vitrectomy). All patients received 0.5 mg ranibizumab IVT injection |
| Measure Participants | 34 |
| 3 Month Absent |
14
15.1%
|
| 3 Month Present |
3
3.2%
|
| 12 Month Absent |
12
12.9%
|
| 12 Month Present |
1
1.1%
|
| Title | Mean Change From Baseline in Change in Central Retinal Thickness for Patients With CNV (Choroidal Neovascularization) and ME (Macular Edema)" |
|---|---|
| Description | CRT in micrometers assessed by Optical Tomography (OCT) at each single study visit. A reduction is thickness indicates an improvement is the lesion area |
| Time Frame | 3 months, 12 month |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population (ITT): all patients who received at least one application of study treatment and had at least one post-baseline efficacy assessment. The ITT population was the main analysis set for efficacy evaluations |
| Arm/Group Title | CNV (Choroidal Neovascularization) | ME (Macular Edema) |
|---|---|---|
| Arm/Group Description | All patients received 0.5 mg ranibizumab IVT injection | All patients received 0.5 mg ranibizumab IVT injection |
| Measure Participants | 93 | 84 |
| 3 Month |
-54.4
(104.55)
|
-84.4
(178.28)
|
| 12 Month |
-56.4
(69.82)
|
-102.0
(220)
|
| Title | Proportion of Patients With Angiographic Leakage |
|---|---|
| Description | Angiography was taken via fluorescein angiography. Any increases of angiographic leakage was counted between baseline and month 3. Also any decreases of angiographic leakage was counted between baseline and 3 month. |
| Time Frame | 3 months, 12 month |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population (ITT): all patients who received at least one application of study treatment and had at least one post-baseline efficacy assessment. The ITT population was the main analysis set for efficacy evaluations. The (n) represent the number of assessed value. |
| Arm/Group Title | CNV (Choroidal Neovascularization) | ME (Macular Edema) | PDR/V |
|---|---|---|---|
| Arm/Group Description | All patients received 0.5 mg ranibizumab IVT injection | All patients received 0.5 mg ranibizumab IVT injection | (Proliferative Diabetic Retinopathy requiring Vitrectomy). All patients received 0.5 mg ranibizumab IVT injection |
| Measure Participants | 93 | 84 | 34 |
| 3 Month Absent |
3
3.2%
|
3
3.6%
|
1
1.8%
|
| 3 Month Present |
3
3.2%
|
3
3.6%
|
0
0%
|
| 12 Month Absent |
3
3.2%
|
1
1.2%
|
|
| 12 Month Present |
2
2.2%
|
0
0%
|
| Title | Ranibizumab Injection |
|---|---|
| Description | Number of ranibizumab injections needed by decreased visual acuity and/or increasing retinal thickness in 3 months of observation period |
| Time Frame | 3 months, 12 month |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety set population: all patients who received at least one application of study treatment and had at least one post-baseline safety assessment. The statement that a patient had no adverse events also constituted a safety assessment. All safety evaluations were carried out on the safety population. |
| Arm/Group Title | CNV (Choroidal Neovascularization) | ME (Macular Edema) | RI/NVG (Rubeosis Iridis and Neovacular Glaucoma) | PDR/V |
|---|---|---|---|---|
| Arm/Group Description | All patients received 0.5 mg ranibizumab IVT injection | All patients received 0.5 mg ranibizumab IVT injection | All patients received 0.5 mg ranibizumab IVT injection | (Proliferative Diabetic Retinopathy requiring Vitrectomy). All patients received 0.5 mg ranibizumab IVT injection |
| Measure Participants | 93 | 84 | 58 | 35 |
| 3 Month |
2.5
(1.03)
|
2.7
(0.88)
|
1.7
(0.79)
|
1.6
(1.0)
|
| 12 Month |
3.8
(2.34)
|
3.9
(2.17)
|
3.0
(1.96)
|
1.7
(1.44)
|
Adverse Events
| Time Frame | up to 3 years | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | AE additional description | |||||||
| Arm/Group Title | Choroidal Neovascularization | Macular Edema | Rubeosis Iridis/ Neovascular Glaucoma | Proliferative Diabetic Retinopathy Requiring Vitrectomy | ||||
| Arm/Group Description | Choroidal neovascularization | Macular edema | Rubeosis iridis/ Neovascular glaucoma | Proliferative diabetic retinopathy requiring vitrectomy | ||||
All Cause Mortality |
||||||||
| Choroidal Neovascularization | Macular Edema | Rubeosis Iridis/ Neovascular Glaucoma | Proliferative Diabetic Retinopathy Requiring Vitrectomy | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/93 (1.1%) | 0/84 (0%) | 7/58 (12.1%) | 1/35 (2.9%) | ||||
Serious Adverse Events |
||||||||
| Choroidal Neovascularization | Macular Edema | Rubeosis Iridis/ Neovascular Glaucoma | Proliferative Diabetic Retinopathy Requiring Vitrectomy | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 11/93 (11.8%) | 15/84 (17.9%) | 31/58 (53.4%) | 14/35 (40%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 0/93 (0%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Cardiac disorders | ||||||||
| Arrhythmia | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Atrial fibrillation | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Cardiac arrest | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 1/35 (2.9%) | ||||
| Cardiac failure | 0/93 (0%) | 0/84 (0%) | 4/58 (6.9%) | 0/35 (0%) | ||||
| Ischaemic cardiomyopathy | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Myocardial ischaemia | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Right ventricular failure | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Eye disorders | ||||||||
| Anterior chamber fibrin (Study eye) | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Blindness (Both eyes) | 0/93 (0%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Cataract (Contralateral eye) | 0/93 (0%) | 2/84 (2.4%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Cataract (Study eye) | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Glaucoma (Contralateral eye) | 0/93 (0%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Glaucoma (Study eye) | 0/93 (0%) | 0/84 (0%) | 2/58 (3.4%) | 1/35 (2.9%) | ||||
| Macular detachment (Both eyes) | 0/93 (0%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Macular fibrosis (Study eye) | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Ocular hypertension (Both eyes) | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Ocular hypertension (Study eye) | 1/93 (1.1%) | 1/84 (1.2%) | 7/58 (12.1%) | 0/35 (0%) | ||||
| Retinal artery occlusion (Both eyes) | 0/93 (0%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Retinal detachment (Study eye) | 0/93 (0%) | 0/84 (0%) | 3/58 (5.2%) | 1/35 (2.9%) | ||||
| Retinal pigment epithelial tear (Study eye) | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Retinal tear (Study eye) | 0/93 (0%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Visual acuity reduced (Both eyes) | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Visual acuity reduced (Study eye) | 1/93 (1.1%) | 0/84 (0%) | 1/58 (1.7%) | 1/35 (2.9%) | ||||
| Vitreous adhesions (Contralateral eye) | 0/93 (0%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Vitreous adhesions (Study eye) | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Vitreous haemorrhage (Contralateral eye) | 0/93 (0%) | 0/84 (0%) | 2/58 (3.4%) | 0/35 (0%) | ||||
| Vitreous haemorrhage (Study eye) | 0/93 (0%) | 2/84 (2.4%) | 2/58 (3.4%) | 1/35 (2.9%) | ||||
| Gastrointestinal disorders | ||||||||
| Duodenal obstruction | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Dysphagia | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Gastrointestinal angiodysplasia | 0/93 (0%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Gastrointestinal dysplasia | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Gastrointestinal haemorrhage | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Pancreatic mass | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| General disorders | ||||||||
| Chest pain | 0/93 (0%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Drug ineffective (Study eye) | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| General physical health deterioration | 0/93 (0%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Hepatobiliary disorders | ||||||||
| Jaundice | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Infections and infestations | ||||||||
| Corneal abscess (Study eye) | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Infection | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Influenza | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Lung infection | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Peritonsillar abscess | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Pneumonia | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Syphilis | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Urinary tract infection | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Craniocerebral injury | 0/93 (0%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Fall | 0/93 (0%) | 0/84 (0%) | 2/58 (3.4%) | 0/35 (0%) | ||||
| Femoral neck fracture | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Foot fracture | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Hip fracture | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Laceration | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Lower limb fracture | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Muscle rupture | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Post procedural complication | 0/93 (0%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Spinal fracture | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Tendon rupture | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Wrist fracture | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Investigations | ||||||||
| Intraocular pressure increased (Study eye) | 0/93 (0%) | 1/84 (1.2%) | 2/58 (3.4%) | 0/35 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Diabetes mellitus | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Diabetes mellitus inadequate control | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 3/35 (8.6%) | ||||
| Hypercalcaemia | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Osteoarthropathy | 0/93 (0%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Adenocarcinoma pancreas | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Choroid melanoma (Study eye) | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Chronic myeloid leukaemia | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Metastases to liver | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Nervous system disorders | ||||||||
| Akinesia | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Cerebrovascular accident | 0/93 (0%) | 2/84 (2.4%) | 0/58 (0%) | 0/35 (0%) | ||||
| Cognitive disorder | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Dizziness | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Hypoglycaemic coma | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Ischaemic stroke | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Vertebrobasilar insufficiency | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Psychiatric disorders | ||||||||
| Alcohol withdrawal syndrome | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Completed suicide | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Hallucination | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Acute kidney injury | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Nephroangiosclerosis | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Renal failure | 0/93 (0%) | 0/84 (0%) | 2/58 (3.4%) | 1/35 (2.9%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Acute respiratory distress syndrome | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Atelectasis | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Hypoxia | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Lung disorder | 0/93 (0%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Pneumonia aspiration | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Pulmonary embolism | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Respiratory arrest | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Respiratory failure | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Diabetic foot | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Vascular disorders | ||||||||
| Arterial disorder | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Extremity necrosis | 0/93 (0%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Hypertension | 0/93 (0%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Peripheral artery stenosis | 0/93 (0%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Peripheral ischaemia | 0/93 (0%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Shock haemorrhagic | 0/93 (0%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Choroidal Neovascularization | Macular Edema | Rubeosis Iridis/ Neovascular Glaucoma | Proliferative Diabetic Retinopathy Requiring Vitrectomy | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 46/93 (49.5%) | 66/84 (78.6%) | 40/58 (69%) | 21/35 (60%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Lymphopenia | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Thrombocytosis | 0/93 (0%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Cardiac disorders | ||||||||
| Myocardial ischaemia | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Tachycardia | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Ear and labyrinth disorders | ||||||||
| Ear discomfort | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Tinnitus | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Vertigo | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Endocrine disorders | ||||||||
| Thyroid mass | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Eye disorders | ||||||||
| Cataract (Study eye) | 0/93 (0%) | 3/84 (3.6%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Conjunctival haemorrhage (Study eye) | 0/93 (0%) | 4/84 (4.8%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Dry eye (Study eye) | 0/93 (0%) | 2/84 (2.4%) | 2/58 (3.4%) | 0/35 (0%) | ||||
| Eye pain (Study eye) | 6/93 (6.5%) | 5/84 (6%) | 7/58 (12.1%) | 3/35 (8.6%) | ||||
| Eye pruritus (Study eye) | 2/93 (2.2%) | 1/84 (1.2%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Ocular hyperaemia (Study eye) | 1/93 (1.1%) | 0/84 (0%) | 1/58 (1.7%) | 1/35 (2.9%) | ||||
| Ocular hypertension (Study eye) | 0/93 (0%) | 0/84 (0%) | 2/58 (3.4%) | 3/35 (8.6%) | ||||
| Punctate keratitis (Study eye) | 1/93 (1.1%) | 0/84 (0%) | 1/58 (1.7%) | 1/35 (2.9%) | ||||
| Ulcerative keratitis (Study eye) | 0/93 (0%) | 1/84 (1.2%) | 2/58 (3.4%) | 2/35 (5.7%) | ||||
| Vision blurred (Study eye) | 2/93 (2.2%) | 1/84 (1.2%) | 0/58 (0%) | 2/35 (5.7%) | ||||
| Visual acuity reduced (Contralateral eye) | 2/93 (2.2%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Visual acuity reduced (Study eye) | 3/93 (3.2%) | 3/84 (3.6%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Allergic keratitis (Study eye) | 0/93 (0%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Anterior chamber fibrin (Study eye) | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Blepharitis (Both eyes) | 1/93 (1.1%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Blepharitis (Contralateral eye) | 1/93 (1.1%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Blepharospasm (Study eye) | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Cataract (Both eyes) | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Cataract (Contralateral eye) | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Cataract subcapsular (Study eye) | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Chalazion (Contralateral eye) | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Choroidal neovascularisation (Contralateral eye) | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Choroiditis (Study eye) | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Conjunctival haemorrhage (Contralateral eye) | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Conjunctival hyperaemia (Both eyes) | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Conjunctival hyperaemia (Study eye) | 1/93 (1.1%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Conjunctival ulcer (Study eye) | 0/93 (0%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Conjunctivitis allergic (Both eyes) | 1/93 (1.1%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Corneal perforation (Study eye) | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Cystoid macular oedema (Study eye) | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Dry eye (Both eyes) | 1/93 (1.1%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Eczema eyelids (Contralateral eye) | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Exophthalmos (Both eyes) | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Eye allergy (Both eyes) | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Eye discharge (Study eye) | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Eye haemorrhage (Study eye) | 0/93 (0%) | 0/84 (0%) | 2/58 (3.4%) | 0/35 (0%) | ||||
| Eye inflammation (Study eye) | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Eye irritation (Both eyes) | 2/93 (2.2%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Eye irritation (Study eye) | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Eye oedema (Study eye) | 0/93 (0%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Eye pain (Both eyes) | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 1/35 (2.9%) | ||||
| Eye pain (Contralateral eye) | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Eye pruritus (Both eyes) | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Eye ulcer (Study eye) | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Eyelid cyst (Contralateral eye) | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Eyelid irritation (Study eye) | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Eyelid myoclonus (Study eye) | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Eyelid pain (Study eye) | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Eyelid ptosis (Study eye) | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Foreign body sensation in eyes (Both eyes) | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Foreign body sensation in eyes (Contralateral eye) | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Foreign body sensation in eyes (Study eye) | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 1/35 (2.9%) | ||||
| Glare (Study eye) | 1/93 (1.1%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Glaucoma (Both eyes) | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Iridocyclitis (Study eye) | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Iris neovascularisation (Contralateral eye) | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Keratitis (Study eye) | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Lacrimation increased (Both eyes) | 0/93 (0%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Macular fibrosis (Study eye) | 2/93 (2.2%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Macular oedema (Study eye) | 1/93 (1.1%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Metamorphopsia (Study eye) | 2/93 (2.2%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Ocular discomfort (Contralateral eye) | 0/93 (0%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Ocular discomfort (Study eye) | 0/93 (0%) | 0/84 (0%) | 2/58 (3.4%) | 0/35 (0%) | ||||
| Ocular hypertension (Both eyes) | 0/93 (0%) | 1/84 (1.2%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Ocular hypertension (Contralateral eye) | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Photophobia (Both eyes) | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Photophobia (Contralateral eye) | 0/93 (0%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Photophobia (Study eye) | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Photopsia (Both eyes) | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Photopsia (Contralateral eye) | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Photopsia (Study eye) | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Punctate keratitis (Contralateral eye) | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Retinal detachment (Study eye) | 1/93 (1.1%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Retinal haemorrhage (Study eye) | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Retinal neovascularisation (Study eye) | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Retinal oedema (Study eye) | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Retinal pigment epithelial tear (Study eye) | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Retinal pigment epitheliopathy (Both eyes) | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Uveitis (Both eyes) | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Vision blurred (Both eyes) | 0/93 (0%) | 0/84 (0%) | 2/58 (3.4%) | 0/35 (0%) | ||||
| Visual acuity reduced (Both eyes) | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Visual impairment (Study eye) | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Vitreous floaters (Both eyes) | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Vitreous floaters (Contralateral eye) | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Vitreous floaters (Study eye) | 1/93 (1.1%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Vitreous haemorrhage (Study eye) | 0/93 (0%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Vitritis (Study eye) | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal pain | 0/93 (0%) | 2/84 (2.4%) | 0/58 (0%) | 0/35 (0%) | ||||
| Abdominal pain upper | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Constipation | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Dental necrosis | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Dyspepsia | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Gastrointestinal disorder | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Gastrooesophageal reflux disease | 1/93 (1.1%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Nausea | 1/93 (1.1%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Noninfective gingivitis | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Pancreatitis acute | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Toothache | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Vomiting | 0/93 (0%) | 1/84 (1.2%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| General disorders | ||||||||
| Asthenia | 0/93 (0%) | 0/84 (0%) | 3/58 (5.2%) | 0/35 (0%) | ||||
| Drug ineffective (Study eye) | 3/93 (3.2%) | 27/84 (32.1%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Fatigue | 2/93 (2.2%) | 3/84 (3.6%) | 4/58 (6.9%) | 0/35 (0%) | ||||
| Face oedema | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Facial pain | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Feeling hot | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Inflammation | 0/93 (0%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Influenza like illness | 0/93 (0%) | 1/84 (1.2%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Injection site ulcer (Study eye) | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Pain | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Pyrexia | 1/93 (1.1%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Secretion discharge (Study eye) | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Hepatobiliary disorders | ||||||||
| Cholelithiasis | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Liver disorder | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Immune system disorders | ||||||||
| Hypersensitivity | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Infections and infestations | ||||||||
| Bronchitis | 1/93 (1.1%) | 3/84 (3.6%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Conjunctivitis (Both eyes) | 1/93 (1.1%) | 1/84 (1.2%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Conjunctivitis (Study eye) | 1/93 (1.1%) | 0/84 (0%) | 1/58 (1.7%) | 1/35 (2.9%) | ||||
| Influenza | 4/93 (4.3%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Sinusitis | 2/93 (2.2%) | 2/84 (2.4%) | 0/58 (0%) | 0/35 (0%) | ||||
| Urinary tract infection | 0/93 (0%) | 2/84 (2.4%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Viral upper respiratory tract infection | 1/93 (1.1%) | 3/84 (3.6%) | 0/58 (0%) | 0/35 (0%) | ||||
| Eye infection (Study eye) | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Genital infection female | 0/93 (0%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Herpes zoster | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Infected bite | 0/93 (0%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Lung infection | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Nasopharyngitis | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Oral herpes | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Post procedural infection (Study eye) | 0/93 (0%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Rhinitis | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Tonsillitis | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Tracheitis | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Upper respiratory tract infection | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Vaginal infection | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Fall | 1/93 (1.1%) | 1/84 (1.2%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Inappropriate schedule of drug administration (Study eye) | 11/93 (11.8%) | 21/84 (25%) | 4/58 (6.9%) | 1/35 (2.9%) | ||||
| Incorrect product storage (Study eye) | 4/93 (4.3%) | 6/84 (7.1%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Bone fissure | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Conjunctival laceration (Study eye) | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Hyphaema (Study eye) | 0/93 (0%) | 0/84 (0%) | 2/58 (3.4%) | 0/35 (0%) | ||||
| Incorrect product storage (Contralateral eye) | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Ligament sprain | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Limb injury | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Maternal exposure during pregnancy | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Rib fracture | 1/93 (1.1%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Wound | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Investigations | ||||||||
| Blood urea increased | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 2/35 (5.7%) | ||||
| Blood bilirubin increased | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Blood creatinine increased | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Eosinophil count increased | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Gamma-glutamyltransferase increased | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Intraocular pressure increased (Contralateral eye) | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Intraocular pressure increased (Study eye) | 0/93 (0%) | 1/84 (1.2%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Neutrophil count increased | 0/93 (0%) | 2/84 (2.4%) | 0/58 (0%) | 0/35 (0%) | ||||
| Red blood cell count increased | 0/93 (0%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| White blood cell count increased | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Diabetes mellitus inadequate control | 0/93 (0%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Folate deficiency | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Gout | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Hypercholesterolaemia | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Hyperkalaemia | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Hypertriglyceridaemia | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 1/93 (1.1%) | 3/84 (3.6%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Back pain | 4/93 (4.3%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Ankylosing spondylitis | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Muscle spasms | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Muscular weakness | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Musculoskeletal chest pain | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Musculoskeletal pain | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Neck pain | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Osteitis | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Osteoporosis | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Polyarthritis | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Tendon pain | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Tendonitis | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Lymphoma cutis | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Nervous system disorders | ||||||||
| Dizziness | 1/93 (1.1%) | 4/84 (4.8%) | 0/58 (0%) | 0/35 (0%) | ||||
| Headache | 7/93 (7.5%) | 4/84 (4.8%) | 2/58 (3.4%) | 0/35 (0%) | ||||
| Carotid artery stenosis | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Migraine | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Migraine with aura | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Neuropathy peripheral | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Transient ischaemic attack | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Visual field defect (Study eye) | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Psychiatric disorders | ||||||||
| Depression | 0/93 (0%) | 1/84 (1.2%) | 2/58 (3.4%) | 0/35 (0%) | ||||
| Affective disorder | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Insomnia | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Diabetic nephropathy | 0/93 (0%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Microalbuminuria | 0/93 (0%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Renal failure | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Reproductive system and breast disorders | ||||||||
| Amenorrhoea | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Prostatitis | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Rhinitis allergic | 2/93 (2.2%) | 0/84 (0%) | 0/58 (0%) | 1/35 (2.9%) | ||||
| Chronic obstructive pulmonary disease | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Cough | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 1/35 (2.9%) | ||||
| Epistaxis | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Lung disorder | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Oropharyngeal pain | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Sinus polyp | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Decubitus ulcer | 0/93 (0%) | 0/84 (0%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Pruritus | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
| Rash | 0/93 (0%) | 2/84 (2.4%) | 0/58 (0%) | 0/35 (0%) | ||||
| Skin lesion | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Vascular disorders | ||||||||
| Haematoma | 0/93 (0%) | 1/84 (1.2%) | 2/58 (3.4%) | 0/35 (0%) | ||||
| Hypertension | 1/93 (1.1%) | 2/84 (2.4%) | 1/58 (1.7%) | 0/35 (0%) | ||||
| Hypotension | 1/93 (1.1%) | 0/84 (0%) | 0/58 (0%) | 0/35 (0%) | ||||
| Peripheral vascular disorder | 0/93 (0%) | 1/84 (1.2%) | 0/58 (0%) | 0/35 (0%) | ||||
Limitations/Caveats
As the study was early terminated, no conclusion could be drawn from this study. The data should be interpreted with cautious as less than half of the patients included in the study (47.0%) completed the visit at Month 12.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 862-778-8300 |
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01908816
Other Study ID Numbers:
- CRFB002GFR02
First Posted:
Jul 26, 2013
Last Update Posted:
Aug 12, 2019
Last Verified:
Jul 1, 2019