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BRIGHTER: Efficacy and Safety of Ranibizumab With or Without Laser in Comparison to Laser in Branch Retinal Vein Occlusion

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01599650
Collaborator
(none)
455
Enrollment
82
Locations
3
Arms
36
Duration (Months)
5.5
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will generate comparative data for 0.5-mg ranibizumab using PRN dosing administered with or without adjunctive laser treatment versus laser photocoagulation (the current standard of care) up to Month 6 in patients with visual impairment due to ME secondary to BRVO. Additionally the results of this study will provide long-term (24-month) safety and efficacy data for ranibizumab, administered with or without adjunctive laser treatment in this indication.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
455 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A 24-month, Phase IIIb, Open-label, Randomized, Active Controlled, 3-arm, Multicenter Study Assessing the Efficacy and Safety of an Individualized, Stabilization-criteria-driven PRN Dosing Regimen With 0.5-mg Ranibizumab Intravitreal Injections Applied as Monotherapy or With Adjunctive Laser Photocoagulation in Comparison to Laser Photocoagulation in Patients With Visual Impairment Due to Macular Edema Secondary to Branch Retinal Vein Occlusion
Study Start Date :
May 1, 2012
Actual Primary Completion Date :
May 1, 2015
Actual Study Completion Date :
May 1, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: 1-ranibizumab monotherapy

Ranibizumab 0.5 mg

Drug: Ranibizumab
Other Names:
  • Lucentis

    		•
    Experimental: 2-ranibizumab with laser

    Ranibizumab 0.5 mg + laser

    Drug: Ranibizumab
    Other Names:
  • Lucentis

    • Procedure: Laser
    laser photocoagulation
    Active Comparator: 3-laser monotherapy

    Laser monotherapy with Ranibizumab 0.5 mg from Month 6

    Procedure: Laser
    laser photocoagulation

    Outcome Measures

    Primary Outcome Measures

    1. Mean Change in Visual Acuity: BCVA Change at Month 6 Compared to Baseline in Patients With Visual Impairment Due to Branch Retinal Vein Occlusion (BRVO) [Baseline, 6 Months]

      Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS) -like chart while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters. For the mean change of best corrected visual acuity at Month 6 compare to Baseline, the 95% confidence interval and P value (related to the null hypothesis that this mean change is equal to zero) based on a t distribution/t test were calculated and assessed by an ANOVA model.

    Secondary Outcome Measures

    1. The Mean Average Change in Visual Acuity From Month 1 Through Month 24 Compared to Baseline [Baseline, 24 Months]

      Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters. (A positive average change from baseline of BCVA indicates improvement): Mean Average Change: for each patient, first average change is calculated as the average of the changes from baseline to Month 1 over Month 24. Then, mean average change is calculated as the average of average changes across all patients.

    2. Number of Ranibizumab Treatments From Day 1 to Month 23 by Treatment Group [Day 1 through Month 23]

      Number of injections provided to the patients during the 23 month period and conducted within FAS with LOCF and observed data.

    3. Mean Average Change in Visual Acuity (BCVA Letters) From Month 1 Through Month 6 [From Baseline through Month 6]

      Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS) -like chart while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters.(A positive average change from baseline of BCVA indicates improvement): Mean Average Change: for each patient, first average change is calculated as the average of the changes from baseline to Month 1 over Month 6. Then, mean average change is calculated as the average of average changes across all patients.

    4. The Mean Change in Visual Acuity BCVA (Letters) From Baseline at Month 12 and Month 24 [Baseline, Month 12 and Month 24]

      Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS) -like chart while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters. For the mean change of best corrected visual acuity at Month 12 and Month 24 compare to Baseline, the 95% confidence interval and P value (related to the null hypothesis that this mean change is equal to zero) based on a t distribution/t test were calculated and were assessed by an ANOVA model.

    5. The Percent of Patients With a Visual Acuity Gain of ≥1, ≥5, ≥10, ≥15, and ≥30 Letters From Baseline up to Month 6 and Month 24, by Visit [Baseline, Month 6 and Month 24]

      BCVA score was based on the number of letters read correctly on the Early Treatment Diabetic retinopathy Study (ETDRS) visual acuity chart assessed at a starting distance of 4 meters. An increased score indicates improvement in acuity. This outcome assessed the number of participants who had improvement of ≥1, ≥5, ≥10, ≥15, and ≥30 letters of visual acuity at Month 6 & Month 24 as compared with baseline, was assessed by an ANOVA model. Endpoints related to the proportion of patients with BCVA letter gain or loss from Baseline was analyzed via stratified Cochran-Mantel-Haenszel test with stratification based on baseline BCVA (baseline BCVA less than or equal to 39, 40 to 59, greater than or equal to 60 letters, treatment groups).

    6. Number of Patients With a BCVA Improvement vs Baseline or Achieving Greater Than or Equal to 73 Letters at Month 6 in the Study Eye [Month 6]

      Best Corrected Visual Acuity (BCVA) was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)-like chart at baseline and Month 6 while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. BCVA above 73 letters at Month 6 indicates a positive outcome.

    7. Number of Patients With a BCVA Improvement vs Baseline or Achieved Greater Than or Equal to 73 Letters at Month 24 in the Study Eye [Month 24]

      Best Corrected Visual Acuity (BCVA) was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)-like chart at baseline and Month 12 while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. BCVA above 73 letters at Month 24 indicates a positive outcome.

    8. The Mean Change in Central Reading Center-assessed Central Subfield Thickness From Month 12 and Month 24 vs. Baseline by Treatment Arm [Month 12 and Month 24]

      Retinal thickness was measured using Optical Coherence Tomography (OCT). The images were reviewed by a central reading center to ensure a standardized evaluation. Stratification was done based on categories of baseline best corrected visual acuity & analysis was based on analysis of variance (ANOVA)

    9. The Mean Change in Patient Reported Outcomes in NEI-VFQ-25 Score (Composite Score and Subscales) at Month 6 and Month 24 Compared to Baseline [Months 6 and 24]

      The survey consists of 25 items representing 11 vision related constructs (general vision, ocular pain, near activities, distance activities, social functioning, mental health, role difficulties, dependency, driving, color vision, peripheral vision) plus a single-item general health rating question. All items are scored so that a high score represents better functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. In this format scores represent the achieved percentage of the total possible score, e.g. a score of 50 represents 50% of the highest possible score.

    10. BCVA (Letters) Mean Average Change From First Ranibizumab Treatment to Month 24 in the Study Eye for Patients Randomized to the Laser Monotherapy Arm [Month 24]

      Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS) -like chart while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters. For the mean change of best corrected visual acuity at Month 24 compare to Baseline, the 95% confidence interval and P value (related to the null hypothesis that this mean change is equal to zero) based on a t distribution/t test were calculated and assessed by an ANOVA model.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Written informed consent must be obtained before any study assessment is performed

    • Diagnosis of visual impairment exclusively due to ME secondary to BRVO

    • BCVA score at Screening and Baseline between 73 and 19 letters (ETDRS)

    Exclusion Criteria:

    • Pregnant or nursing (lactating) women

    • Stroke or myocardial infarction less than 3 months before Screening

    • Uncontrolled blood pressure defined as systolic value of >160 mm Hg or diastolic value of >100 mm Hg at Screening or Baseline.

    • Any active periocular or ocular infection or inflammation at Screening or Baseline in either eye

    • Uncontrolled glaucoma at Screening or Baseline or diagnosed within 6 months before Baseline in either eye

    • Neovascularization of the iris or neovascular glaucoma in the study eye

    • Use of any systemic antivascular endothelial growth factor (anti-VEGF) drugs within 6 months before Baseline

    • Panretinal laser photocoagulation within 3 months before Baseline or anticipated or scheduled within the next 3 months following Baseline in the study eye

    • Focal or grid laser photocoagulation within 4 months before Baseline in the study eye

    • Use of intra- or periocular corticosteroids (including sub-Tenon) within 3 months before Screening in the study eye

    • Any use of intraocular corticosteroid implants (eg, dexamethasone [Ozurdex®], fluocinolone acetonide [Iluvien®]) in the study eye

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Novartis Investigative Site Parramatta New South Wales Australia 2150
    2 Novartis Investigative Site Sydney New South Wales Australia 2000
    3 Novartis Investigative Site Melbourne Victoria Australia 3002
    4 Novartis Investigative Site Nedlands Western Australia Australia 6009
    5 Novartis Investigative Site Calgary Alberta Canada T2H0C8
    6 Novartis Investigative Site Vancouver British Columbia Canada V5Z 1M9
    7 Novartis Investigative Site Victoria British Columbia Canada V8V 4X3
    8 Novartis Investigative Site Halifax Nova Scotia Canada B3H 2Y9
    9 Novartis Investigative Site London Ontario Canada N6A 4G5
    10 Novartis Investigative Site Boisbriand Quebec Canada J7H 1S6
    11 Novartis Investigative Site Montreal Quebec Canada H1T 2M4
    12 Novartis Investigative Site Olomouc Czech Republic 775 20
    13 Novartis Investigative Site Praha 10 Czech Republic 100 34
    14 Novartis Investigative Site Glostrup Denmark DK-2600
    15 Novartis Investigative Site Dijon France 21033
    16 Novartis Investigative Site Lyon France 69003
    17 Novartis Investigative Site Nice France 06000
    18 Novartis Investigative Site Paris cedex 10 France 75010
    19 Novartis Investigative Site Paris Cedex 19 France 75940
    20 Novartis Investigative Site Paris France
    21 Novartis Investigative Site Athens GR Greece 124 62
    22 Novartis Investigative Site Heraklion Crete GR Greece 711 10
    23 Novartis Investigative Site Larissa GR Greece 411 10
    24 Novartis Investigative Site Thessaloniki GR Greece 546 29
    25 Novartis Investigative Site Patras Greece 26504
    26 Novartis Investigative Site Thessaloniki Greece GR 54636
    27 Novartis Investigative Site Budapest Hungary 1133
    28 Novartis Investigative Site Budapest Hungary H-1083
    29 Novartis Investigative Site Debrecen Hungary 4032
    30 Novartis Investigative Site Dublin 7 Ireland
    31 Novartis Investigative Site Dublin Ireland
    32 Novartis Investigative Site Bologna BO Italy 40138
    33 Novartis Investigative Site Firenze FI Italy 50134
    34 Novartis Investigative Site Milano MI Italy 20100
    35 Novartis Investigative Site Milano MI Italy 20132
    36 Novartis Investigative Site Roma RM Italy 00144
    37 Novartis Investigative Site Torino TO Italy 10122
    38 Novartis Investigative Site Bari Italy 70124
    39 Novartis Investigative Site Udine Italy 33100
    40 Novartis Investigative Site Leiden 2333 ZA Netherlands 2333
    41 Novartis Investigative Site Rotterdam Netherlands 3011 BH
    42 Novartis Investigative Site Tilburg Netherlands 5022 GC
    43 Novartis Investigative Site Bielsko-Biala Poland 43-300
    44 Novartis Investigative Site Gdansk Poland 80-809
    45 Novartis Investigative Site Kraków Poland 31-501
    46 Novartis Investigative Site Lublin Poland 20-079
    47 Novartis Investigative Site Warszawa Poland 02-005
    48 Novartis Investigative Site Wroclaw Poland 50-556
    49 Novartis Investigative Site Coimbra Portugal 3000-354
    50 Novartis Investigative Site Coimbra Portugal 3030-163
    51 Novartis Investigative Site Lisboa Portugal 1050-085
    52 Novartis Investigative Site Lisboa Portugal 1349-019
    53 Novartis Investigative Site Porto Portugal 4099-001
    54 Novartis Investigative Site Porto Portugal 4200-319
    55 Novartis Investigative Site Zilina Slovak Republic Slovakia 010 01
    56 Novartis Investigative Site Banska Bystrica Slovakia 975 17
    57 Novartis Investigative Site Bratislava Slovakia 826 06
    58 Novartis Investigative Site Bratislava Slovakia 851 07
    59 Novartis Investigative Site Valladolid Castilla y Leon Spain 47011
    60 Novartis Investigative Site Barcelona Cataluña Spain 08022
    61 Novartis Investigative Site Barcelona Cataluña Spain
    62 Novartis Investigative Site L´Hospitalet de Llobregat Cataluña Spain 08907
    63 Novartis Investigative Site Alicante Comunidad Valenciana Spain 03016
    64 Novartis Investigative Site Valencia Comunidad Valenciana Spain 46014
    65 Novartis Investigative Site Valencia Comunidad Valenciana Spain 46015
    66 Novartis Investigative Site Santiago de Compostela Galicia Spain 15706
    67 Novartis Investigative Site Bilbao Pais Vasco Spain 48006
    68 Novartis Investigative Site Madrid Spain 28046
    69 Novartis Investigative Site Örebro Sweden 701 85
    70 Novartis Investigative Site Bern Switzerland 3012
    71 Novartis Investigative Site Lausanne Switzerland 1007
    72 Novartis Investigative Site Olten Switzerland 4600
    73 Novartis Investigative Site Zuerich Switzerland 8063
    74 Novartis Investigative Site Frimley Surrey United Kingdom GU16 7UJ
    75 Novartis Investigative Site Belfast United Kingdom BT12 6BA
    76 Novartis Investigative Site Birmingham United Kingdom B9 5SS
    77 Novartis Investigative Site Bristol United Kingdom BS1 2LX
    78 Novartis Investigative Site London United Kingdom EC1V 2PD
    79 Novartis Investigative Site London United Kingdom NW1 5QH
    80 Novartis Investigative Site Newcastle upon Tyne United Kingdom NE1 4LP
    81 Novartis Investigative Site Plymouth United Kingdom PL4 6PL
    82 Novartis Investigative Site Southampton United Kingdom SO16 6YD

    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:
    NCT01599650
    Other Study ID Numbers:
    • CRFB002E2402
    • 2011-002859-34
    First Posted:
    May 16, 2012
    Last Update Posted:
    Nov 10, 2016
    Last Verified:
    Sep 1, 2016
    Keywords provided by Novartis Pharmaceuticals
    Macular Edema, Branch Retinal Vein Occlusion, visual impairment
    Additional relevant MeSH terms:
    Retinal Vein Occlusion
    Ranibizumab

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title 1-ranibizumab Monotherapy 2-ranibizumab With Laser 3-laser Monotherapy
    Arm/Group Description laser therapy + Ranibizumab 0.5 mg Ranibizumab 0.5 mg + laser after 6 months, laser patients could be treated with ranibizumab
    Period Title: Overall Study
    STARTED 183 180 92
    Completed 6 Mos 174 170 80
    COMPLETED 161 154 65
    NOT COMPLETED 22 26 27

    Baseline Characteristics

    Arm/Group Title 1-ranibizumab Monotherapy 2-ranibizumab With Laser 3-laser Monotherapy Total
    Arm/Group Description laser therapy + Ranibizumab 0.5 mg Ranibizumab 0.5 mg + laser after 6 months, laser patients could be treated with ranibizumab Total of all reporting groups
    Overall Participants 183 180 92 455
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    64.7
    (10.34)
    67.3
    (10.41)
    67.7
    (9.67)
    66.3
    (10.30)
    Sex: Female, Male (Count of Participants)
    Female
    90
    49.2%
    84
    46.7%
    55
    59.8%
    229
    50.3%
    Male
    93
    50.8%
    96
    53.3%
    37
    40.2%
    226
    49.7%

    Outcome Measures

    1. Primary Outcome
    Title Mean Change in Visual Acuity: BCVA Change at Month 6 Compared to Baseline in Patients With Visual Impairment Due to Branch Retinal Vein Occlusion (BRVO)
    Description Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS) -like chart while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters. For the mean change of best corrected visual acuity at Month 6 compare to Baseline, the 95% confidence interval and P value (related to the null hypothesis that this mean change is equal to zero) based on a t distribution/t test were calculated and assessed by an ANOVA model.
    Time Frame Baseline, 6 Months

    Outcome Measure Data

    Analysis Population Description
    analysis for change consists of the group that had a baseline and 6 month data point
    Arm/Group Title 1-ranibizumab Monotherapy 2-ranibizumab With Laser 3-laser Monotherapy
    Arm/Group Description laser therapy + Ranibizumab 0.5 mg Ranibizumab 0.5 mg + laser after 6 months, laser patients could be treated with ranibizumab
    Measure Participants 180 178 90
    Baseline
    59.5
    (11.78)
    56.6
    (13.19)
    56.8
    (13.86)
    Month 6
    74.3
    (12.27)
    71.4
    (14.43)
    62.8
    (14.08)
    Change from Baseline atMonth 6
    14.8
    (10.70)
    14.8
    (11.13)
    6.0
    (14.27)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection 1-ranibizumab Monotherapy, 3-laser Monotherapy
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter difference in LS mean
    Estimated Value 10.0
    Confidence Interval (2-Sided) 95%
    7.3 to 12.8
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.41
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection 2-ranibizumab With Laser, 3-laser Monotherapy
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter difference in LS Means
    Estimated Value 8.7
    Confidence Interval (2-Sided) 95%
    5.8 to 11.6
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.46
    Estimation Comments
    2. Secondary Outcome
    Title The Mean Average Change in Visual Acuity From Month 1 Through Month 24 Compared to Baseline
    Description Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters. (A positive average change from baseline of BCVA indicates improvement): Mean Average Change: for each patient, first average change is calculated as the average of the changes from baseline to Month 1 over Month 24. Then, mean average change is calculated as the average of average changes across all patients.
    Time Frame Baseline, 24 Months

    Outcome Measure Data

    Analysis Population Description
    analysis for change consists of the group that had a baseline and 24 month data point
    Arm/Group Title 1-ranibizumab Monotherapy 2-ranibizumab With Laser 3-laser Monotherapy
    Arm/Group Description laser therapy + Ranibizumab 0.5 mg Ranibizumab 0.5 mg + laser after 6 months, laser patients could be treated with ranibizumab
    Measure Participants 180 178 90
    Baseline
    59.5
    (11.78)
    56.6
    (13.19)
    56.8
    (13.86)
    Average Month 1 toMonth 24
    74.5
    (12.11)
    72.0
    (13.56)
    65.9
    (13.24)
    Change from Baseline
    15.0
    (10.86)
    15.4
    (10.76)
    9.1
    (13.49)
    3. Secondary Outcome
    Title Number of Ranibizumab Treatments From Day 1 to Month 23 by Treatment Group
    Description Number of injections provided to the patients during the 23 month period and conducted within FAS with LOCF and observed data.
    Time Frame Day 1 through Month 23

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title 1-ranibizumab Monotherapy 2-ranibizumab With Laser
    Arm/Group Description laser therapy + Ranibizumab 0.5 mg Ranibizumab 0.5 mg + laser
    Measure Participants 180 178
    Mean (Standard Deviation) [treatments]
    11.4
    (5.76)
    11.3
    (6.03)
    4. Secondary Outcome
    Title Mean Average Change in Visual Acuity (BCVA Letters) From Month 1 Through Month 6
    Description Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS) -like chart while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters.(A positive average change from baseline of BCVA indicates improvement): Mean Average Change: for each patient, first average change is calculated as the average of the changes from baseline to Month 1 over Month 6. Then, mean average change is calculated as the average of average changes across all patients.
    Time Frame From Baseline through Month 6

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title 1-ranibizumab Monotherapy 2-ranibizumab With Laser 3-laser Monotherapy
    Arm/Group Description laser therapy + Ranibizumab 0.5 mg Ranibizumab 0.5 mg + laser after 6 months, laser patients could be treated with ranibizumab
    Measure Participants 180 178 90
    Baseline
    59.5
    (11.78)
    56.6
    (13.19)
    56.8
    (13.86)
    Average Month 1 to Month 6
    72.7
    (11.49)
    69.7
    (13.38)
    61.7
    (12.66)
    Change from Baseline
    13.2
    (9.60)
    13.2
    (9.89)
    4.8
    (11.69)
    5. Secondary Outcome
    Title The Mean Change in Visual Acuity BCVA (Letters) From Baseline at Month 12 and Month 24
    Description Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS) -like chart while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters. For the mean change of best corrected visual acuity at Month 12 and Month 24 compare to Baseline, the 95% confidence interval and P value (related to the null hypothesis that this mean change is equal to zero) based on a t distribution/t test were calculated and were assessed by an ANOVA model.
    Time Frame Baseline, Month 12 and Month 24

    Outcome Measure Data

    Analysis Population Description
    Full Analysis set
    Arm/Group Title 1-ranibizumab Monotherapy 2-ranibizumab With Laser 3-laser Monotherapy
    Arm/Group Description laser therapy + Ranibizumab 0.5 mg Ranibizumab 0.5 mg + laser after 6 months, laser patients could be treated with ranibizumab
    Measure Participants 180 178 90
    Baseline
    59.5
    (11.78)
    56.6
    (13.19)
    56.8
    (13.86)
    Month 12
    74.9
    (12.87)
    72.3
    (15.31)
    66.8
    (13.87)
    Change from baseline Month 12
    15.4
    (12.25)
    15.7
    (13.12)
    10.0
    (14.33)
    Month 24
    75.0
    (14.65)
    73.9
    (14.59)
    68.4
    (15.26)
    Change from baseline Month 24
    15.5
    (13.91)
    17.3
    (12.61)
    11.6
    (16.09)
    6. Secondary Outcome
    Title The Percent of Patients With a Visual Acuity Gain of ≥1, ≥5, ≥10, ≥15, and ≥30 Letters From Baseline up to Month 6 and Month 24, by Visit
    Description BCVA score was based on the number of letters read correctly on the Early Treatment Diabetic retinopathy Study (ETDRS) visual acuity chart assessed at a starting distance of 4 meters. An increased score indicates improvement in acuity. This outcome assessed the number of participants who had improvement of ≥1, ≥5, ≥10, ≥15, and ≥30 letters of visual acuity at Month 6 & Month 24 as compared with baseline, was assessed by an ANOVA model. Endpoints related to the proportion of patients with BCVA letter gain or loss from Baseline was analyzed via stratified Cochran-Mantel-Haenszel test with stratification based on baseline BCVA (baseline BCVA less than or equal to 39, 40 to 59, greater than or equal to 60 letters, treatment groups).
    Time Frame Baseline, Month 6 and Month 24

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title 1-ranibizumab Monotherapy 2-ranibizumab With Laser 3-laser Monotherapy
    Arm/Group Description laser therapy + Ranibizumab 0.5 mg Ranibizumab 0.5 mg + laser after 6 months, laser patients could be treated with ranibizumab
    Measure Participants 180 178 90
    BCVA improvement of >= 1 lettermonth 6
    93.3
    96.1
    63.3
    BCVA improvement of >= 1 lettermonth 24
    89.4
    93.8
    77.8
    BCVA improvement of >= 5 lettersmonth 6
    86.1
    88.2
    50.0
    BCVA improvement of >= 5 lettersmonth 24
    83.3
    89.3
    70.0
    BCVA improvement of >= 10 lettersmonth 6
    66.7
    68.5
    41.1
    BCVA improvement of >= 10 lettersmonth 24
    71.1
    75.8
    60.0
    BCVA improvement of >= 15 lettersmonth 6
    45.0
    47.2
    27.8
    BCVA improvement of >= 15 lettersmonth 24
    52.8
    59.6
    43.3
    BCVA improvement of >= 30 lettersmonth 6
    10.0
    9.6
    3.3
    BCVA improvement of >= 30 lettersmonth 24
    13.3
    14.0
    11.1
    7. Secondary Outcome
    Title Number of Patients With a BCVA Improvement vs Baseline or Achieving Greater Than or Equal to 73 Letters at Month 6 in the Study Eye
    Description Best Corrected Visual Acuity (BCVA) was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)-like chart at baseline and Month 6 while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. BCVA above 73 letters at Month 6 indicates a positive outcome.
    Time Frame Month 6

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title 1-ranibizumab Monotherapy 2-ranibizumab With Laser 3-laser Monotherapy
    Arm/Group Description laser therapy + Ranibizumab 0.5 mg Ranibizumab 0.5 mg + laser after 6 months, laser patients could be treated with ranibizumab
    Measure Participants 180 178 90
    BCVA improvement of ≥ 1 letter
    168
    91.8%
    171
    95%
    57
    62%
    BCVA improvement of ≥ 5 letters N
    155
    84.7%
    157
    87.2%
    45
    48.9%
    BCVA improvement of ≥ 10 letters
    120
    65.6%
    122
    67.8%
    37
    40.2%
    BCVA improvement of ≥ 15 letters
    81
    44.3%
    84
    46.7%
    25
    27.2%
    BCVA improvement of ≥ 30 letters
    18
    9.8%
    17
    9.4%
    3
    3.3%
    BCVA score ≥ 73 letters
    118
    64.5%
    97
    53.9%
    28
    30.4%
    8. Secondary Outcome
    Title Number of Patients With a BCVA Improvement vs Baseline or Achieved Greater Than or Equal to 73 Letters at Month 24 in the Study Eye
    Description Best Corrected Visual Acuity (BCVA) was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)-like chart at baseline and Month 12 while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. BCVA above 73 letters at Month 24 indicates a positive outcome.
    Time Frame Month 24

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title 1-ranibizumab Monotherapy 2-ranibizumab With Laser 3-laser Monotherapy
    Arm/Group Description laser therapy + Ranibizumab 0.5 mg Ranibizumab 0.5 mg + laser after 6 months, laser patients could be treated with ranibizumab
    Measure Participants 180 178 90
    BCVA improvement of ≥ 1 letter
    161
    88%
    167
    92.8%
    70
    76.1%
    BCVA improvement of ≥ 5 letters
    150
    82%
    159
    88.3%
    63
    68.5%
    BCVA improvement of ≥ 10 letters
    129
    70.5%
    135
    75%
    54
    58.7%
    BCVA improvement of ≥ 15 letters
    95
    51.9%
    106
    58.9%
    39
    42.4%
    BCVA improvement of ≥ 30 letters
    24
    13.1%
    25
    13.9%
    10
    10.9%
    BCVA score ≥ 73 letters
    119
    65%
    114
    63.3%
    41
    44.6%
    9. Secondary Outcome
    Title The Mean Change in Central Reading Center-assessed Central Subfield Thickness From Month 12 and Month 24 vs. Baseline by Treatment Arm
    Description Retinal thickness was measured using Optical Coherence Tomography (OCT). The images were reviewed by a central reading center to ensure a standardized evaluation. Stratification was done based on categories of baseline best corrected visual acuity & analysis was based on analysis of variance (ANOVA)
    Time Frame Month 12 and Month 24

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title 1-ranibizumab Monotherapy 2-ranibizumab With Laser 3-laser Monotherapy
    Arm/Group Description laser therapy + Ranibizumab 0.5 mg Ranibizumab 0.5 mg + laser after 6 months, laser patients could be treated with ranibizumab
    Measure Participants 180 178 90
    month 12
    -215.9
    (12.83)
    -242.5
    (14.14)
    -203.9
    (22.22)
    month 24
    -228.1
    (12.65)
    -261.7
    (15.20)
    -232.7
    (24.38)
    10. Secondary Outcome
    Title The Mean Change in Patient Reported Outcomes in NEI-VFQ-25 Score (Composite Score and Subscales) at Month 6 and Month 24 Compared to Baseline
    Description The survey consists of 25 items representing 11 vision related constructs (general vision, ocular pain, near activities, distance activities, social functioning, mental health, role difficulties, dependency, driving, color vision, peripheral vision) plus a single-item general health rating question. All items are scored so that a high score represents better functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. In this format scores represent the achieved percentage of the total possible score, e.g. a score of 50 represents 50% of the highest possible score.
    Time Frame Months 6 and 24

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title 1-ranibizumab Monotherapy 2-ranibizumab With Laser 3-laser Monotherapy
    Arm/Group Description laser therapy + Ranibizumab 0.5 mg Ranibizumab 0.5 mg + laser after 6 months, laser patients could be treated with ranibizumab
    Measure Participants 180 178 90
    month 6 composite score
    5.6
    (9.56)
    4.2
    (10.41)
    3.7
    (12.12)
    month 24 composite score
    8.0
    (11.78)
    5.0
    (11.44)
    4.9
    (14.79)
    11. Secondary Outcome
    Title BCVA (Letters) Mean Average Change From First Ranibizumab Treatment to Month 24 in the Study Eye for Patients Randomized to the Laser Monotherapy Arm
    Description Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS) -like chart while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters. For the mean change of best corrected visual acuity at Month 24 compare to Baseline, the 95% confidence interval and P value (related to the null hypothesis that this mean change is equal to zero) based on a t distribution/t test were calculated and assessed by an ANOVA model.
    Time Frame Month 24

    Outcome Measure Data

    Analysis Population Description
    Randomized set
    Arm/Group Title 3- Laser Monotherapy
    Arm/Group Description laser therapy + Ranibizumab 0.5 mg after Month 6
    Measure Participants 66
    Value at 1st Ranibizumab treatment
    61.7
    (12.21)
    Average post 1st treatment through Month 24
    68.16
    (11.84)
    Change from 1st Ranibizumab treatment
    6.49
    (7.83)

    Adverse Events

    Time Frame [1] Safety set was summarized based on actual treatment received. There were 3 laser monotherapy patients who received ranibizumab and 1 ranibizumab patient who received laser treatment which resulted in percentages > 100% for the ranibizumab + laser arm.
    Adverse Event Reporting Description
    Arm/Group Title Ranibizumab 0.5mg Ranibizumab 0.5mg + Laser Laser Monotherapy With Ranibizumab 0.5 mg From Month 6 Laser Monotherapy Without Ranibizumab 0.5 mg From Month 6
    Arm/Group Description Ranibizumab 0.5mg Ranibizumab 0.5mg + Laser [1] Safety set was summarized based on actual treatment received. There were 3 laser monotherapy patients who received ranibizumab and 1 ranibizumab patient who received laser treatment which resulted in percentages > 100% for the ranibizumab + laser arm. Laser monotherapy with Ranibizumab 0.5 mg from Month 6 Laser monotherapy without Ranibizumab 0.5 mg from Month 6
    All Cause Mortality
    Ranibizumab 0.5mg Ranibizumab 0.5mg + Laser Laser Monotherapy With Ranibizumab 0.5 mg From Month 6 Laser Monotherapy Without Ranibizumab 0.5 mg From Month 6
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Ranibizumab 0.5mg Ranibizumab 0.5mg + Laser Laser Monotherapy With Ranibizumab 0.5 mg From Month 6 Laser Monotherapy Without Ranibizumab 0.5 mg From Month 6
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 30/180 (16.7%) 33/183 (18%) 10/63 (15.9%) 3/25 (12%)
    Cardiac disorders
    Acute coronary syndrome 1/180 (0.6%) 0/183 (0%) 0/63 (0%) 0/25 (0%)
    Angina pectoris 0/180 (0%) 0/183 (0%) 1/63 (1.6%) 0/25 (0%)
    Aortic valve incompetence 1/180 (0.6%) 0/183 (0%) 0/63 (0%) 0/25 (0%)
    Arrhythmia 0/180 (0%) 0/183 (0%) 1/63 (1.6%) 0/25 (0%)
    Arteriosclerosis coronary artery 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Atrial fibrillation 3/180 (1.7%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Atrioventricular block second degree 1/180 (0.6%) 0/183 (0%) 1/63 (1.6%) 0/25 (0%)
    Bradycardia 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Cardiac arrest 0/180 (0%) 0/183 (0%) 1/63 (1.6%) 0/25 (0%)
    Cardiac failure 1/180 (0.6%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Coronary artery embolism 1/180 (0.6%) 0/183 (0%) 0/63 (0%) 0/25 (0%)
    Myocardial infarction 1/180 (0.6%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Myocardial ischaemia 1/180 (0.6%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Tachycardia 1/180 (0.6%) 0/183 (0%) 0/63 (0%) 0/25 (0%)
    Eye disorders
    Cataract (Fellow untreated eye) 1/180 (0.6%) 0/183 (0%) 0/63 (0%) 0/25 (0%)
    Cataract (Study eye) 1/180 (0.6%) 0/183 (0%) 0/63 (0%) 0/25 (0%)
    Macular fibrosis (Study eye) 0/180 (0%) 0/183 (0%) 1/63 (1.6%) 0/25 (0%)
    Macular hole (Study eye) 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Retinal aneurysm (Fellow untreated eye) 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Retinopathy (Study eye) 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Visual acuity reduced (Study eye) 1/180 (0.6%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Vitreous haemorrhage (Study eye) 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Gastrointestinal disorders
    Diverticulum intestinal haemorrhagic 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Dyspepsia 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Gastric ulcer 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Inguinal hernia 1/180 (0.6%) 0/183 (0%) 0/63 (0%) 0/25 (0%)
    Intestinal polyp 1/180 (0.6%) 0/183 (0%) 0/63 (0%) 0/25 (0%)
    Large intestine polyp 1/180 (0.6%) 0/183 (0%) 0/63 (0%) 0/25 (0%)
    Hepatobiliary disorders
    Bile duct stone 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Cholelithiasis 2/180 (1.1%) 2/183 (1.1%) 0/63 (0%) 0/25 (0%)
    Gallbladder disorder 1/180 (0.6%) 0/183 (0%) 0/63 (0%) 1/25 (4%)
    Hepatic mass 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Jaundice 1/180 (0.6%) 0/183 (0%) 0/63 (0%) 0/25 (0%)
    Infections and infestations
    Appendicitis 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Bronchitis 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Dengue fever 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Lower respiratory tract infection 1/180 (0.6%) 0/183 (0%) 1/63 (1.6%) 0/25 (0%)
    Perichondritis 0/180 (0%) 0/183 (0%) 1/63 (1.6%) 0/25 (0%)
    Pneumonia 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 1/25 (4%)
    Respiratory tract infection 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Septic shock 1/180 (0.6%) 0/183 (0%) 0/63 (0%) 0/25 (0%)
    Injury, poisoning and procedural complications
    Facial bones fracture (Fellow untreated eye) 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Femur fracture 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Head injury 1/180 (0.6%) 0/183 (0%) 0/63 (0%) 0/25 (0%)
    Hip fracture 0/180 (0%) 0/183 (0%) 0/63 (0%) 1/25 (4%)
    Lumbar vertebral fracture 1/180 (0.6%) 0/183 (0%) 0/63 (0%) 0/25 (0%)
    Pelvic fracture 1/180 (0.6%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Periprosthetic fracture 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Investigations
    Intraocular pressure increased (Fellow untreated eye) 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Intraocular pressure increased (Study eye) 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Metabolism and nutrition disorders
    Hyperkalaemia 0/180 (0%) 0/183 (0%) 1/63 (1.6%) 0/25 (0%)
    Hyponatraemia 1/180 (0.6%) 0/183 (0%) 0/63 (0%) 0/25 (0%)
    Musculoskeletal and connective tissue disorders
    Back pain 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Intervertebral disc protrusion 1/180 (0.6%) 0/183 (0%) 0/63 (0%) 0/25 (0%)
    Osteoarthritis 1/180 (0.6%) 0/183 (0%) 0/63 (0%) 0/25 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of colon 1/180 (0.6%) 0/183 (0%) 0/63 (0%) 0/25 (0%)
    Basal cell carcinoma 1/180 (0.6%) 0/183 (0%) 0/63 (0%) 0/25 (0%)
    Colorectal cancer 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Gastrointestinal carcinoma 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Lung neoplasm malignant 0/180 (0%) 0/183 (0%) 1/63 (1.6%) 0/25 (0%)
    Prostate cancer 1/180 (0.6%) 0/183 (0%) 0/63 (0%) 0/25 (0%)
    Thyroid cancer 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Nervous system disorders
    Amnesia 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Basal ganglia stroke 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Cerebrovascular accident 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Dizziness 1/180 (0.6%) 0/183 (0%) 0/63 (0%) 0/25 (0%)
    Dysarthria 1/180 (0.6%) 0/183 (0%) 0/63 (0%) 0/25 (0%)
    Headache 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Ischaemic stroke 1/180 (0.6%) 0/183 (0%) 1/63 (1.6%) 0/25 (0%)
    Syncope 1/180 (0.6%) 0/183 (0%) 0/63 (0%) 0/25 (0%)
    Transient ischaemic attack 0/180 (0%) 1/183 (0.5%) 1/63 (1.6%) 0/25 (0%)
    Psychiatric disorders
    Anxiety 1/180 (0.6%) 0/183 (0%) 0/63 (0%) 0/25 (0%)
    Burnout syndrome 0/180 (0%) 0/183 (0%) 1/63 (1.6%) 0/25 (0%)
    Depression 1/180 (0.6%) 0/183 (0%) 0/63 (0%) 0/25 (0%)
    Renal and urinary disorders
    Prerenal failure 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Renal failure chronic 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Urethral stenosis 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Reproductive system and breast disorders
    Benign prostatic hyperplasia 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Ovarian cyst 1/180 (0.6%) 0/183 (0%) 0/63 (0%) 0/25 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 1/180 (0.6%) 0/183 (0%) 0/63 (0%) 0/25 (0%)
    Dyspnoea 1/180 (0.6%) 0/183 (0%) 0/63 (0%) 0/25 (0%)
    Skin and subcutaneous tissue disorders
    Dermatitis bullous 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Vascular disorders
    Aortic aneurysm 0/180 (0%) 0/183 (0%) 1/63 (1.6%) 0/25 (0%)
    Hypertension 1/180 (0.6%) 0/183 (0%) 1/63 (1.6%) 0/25 (0%)
    Hypovolaemic shock 0/180 (0%) 0/183 (0%) 1/63 (1.6%) 0/25 (0%)
    Other (Not Including Serious) Adverse Events
    Ranibizumab 0.5mg Ranibizumab 0.5mg + Laser Laser Monotherapy With Ranibizumab 0.5 mg From Month 6 Laser Monotherapy Without Ranibizumab 0.5 mg From Month 6
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 112/180 (62.2%) 121/183 (66.1%) 40/63 (63.5%) 14/25 (56%)
    Ear and labyrinth disorders
    Vertigo 3/180 (1.7%) 1/183 (0.5%) 2/63 (3.2%) 0/25 (0%)
    Eye disorders
    Blepharitis (Fellow untreated eye) 2/180 (1.1%) 11/183 (6%) 0/63 (0%) 0/25 (0%)
    Blepharitis (Study eye) 3/180 (1.7%) 11/183 (6%) 1/63 (1.6%) 0/25 (0%)
    Cataract (Fellow untreated eye) 3/180 (1.7%) 6/183 (3.3%) 0/63 (0%) 0/25 (0%)
    Cataract (Study eye) 8/180 (4.4%) 3/183 (1.6%) 1/63 (1.6%) 0/25 (0%)
    Conjunctival haemorrhage (Study eye) 15/180 (8.3%) 15/183 (8.2%) 5/63 (7.9%) 0/25 (0%)
    Conjunctivitis allergic (Study eye) 5/180 (2.8%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Corneal erosion (Study eye) 0/180 (0%) 4/183 (2.2%) 0/63 (0%) 0/25 (0%)
    Cystoid macular oedema (Study eye) 4/180 (2.2%) 1/183 (0.5%) 1/63 (1.6%) 0/25 (0%)
    Dry eye (Fellow untreated eye) 9/180 (5%) 3/183 (1.6%) 2/63 (3.2%) 0/25 (0%)
    Dry eye (Study eye) 10/180 (5.6%) 3/183 (1.6%) 2/63 (3.2%) 0/25 (0%)
    Eye irritation (Study eye) 4/180 (2.2%) 7/183 (3.8%) 1/63 (1.6%) 0/25 (0%)
    Eye pain (Study eye) 18/180 (10%) 21/183 (11.5%) 3/63 (4.8%) 0/25 (0%)
    Eye pruritus (Study eye) 4/180 (2.2%) 2/183 (1.1%) 2/63 (3.2%) 0/25 (0%)
    Eyelid oedema (Study eye) 4/180 (2.2%) 3/183 (1.6%) 0/63 (0%) 0/25 (0%)
    Glaucoma (Study eye) 4/180 (2.2%) 2/183 (1.1%) 0/63 (0%) 0/25 (0%)
    Lacrimation increased (Study eye) 5/180 (2.8%) 2/183 (1.1%) 1/63 (1.6%) 0/25 (0%)
    Macular fibrosis (Study eye) 8/180 (4.4%) 7/183 (3.8%) 1/63 (1.6%) 0/25 (0%)
    Macular oedema (Study eye) 4/180 (2.2%) 5/183 (2.7%) 3/63 (4.8%) 1/25 (4%)
    Metamorphopsia (Study eye) 1/180 (0.6%) 0/183 (0%) 2/63 (3.2%) 0/25 (0%)
    Ocular hyperaemia (Study eye) 7/180 (3.9%) 8/183 (4.4%) 0/63 (0%) 0/25 (0%)
    Ocular hypertension (Fellow untreated eye) 3/180 (1.7%) 4/183 (2.2%) 1/63 (1.6%) 1/25 (4%)
    Ocular hypertension (Study eye) 5/180 (2.8%) 4/183 (2.2%) 0/63 (0%) 2/25 (8%)
    Photopsia (Study eye) 2/180 (1.1%) 2/183 (1.1%) 2/63 (3.2%) 0/25 (0%)
    Posterior capsule opacification (Study eye) 2/180 (1.1%) 0/183 (0%) 2/63 (3.2%) 0/25 (0%)
    Punctate keratitis (Study eye) 6/180 (3.3%) 1/183 (0.5%) 1/63 (1.6%) 0/25 (0%)
    Retinal haemorrhage (Study eye) 5/180 (2.8%) 3/183 (1.6%) 2/63 (3.2%) 1/25 (4%)
    Retinal ischaemia (Study eye) 2/180 (1.1%) 4/183 (2.2%) 1/63 (1.6%) 0/25 (0%)
    Retinal neovascularisation (Study eye) 2/180 (1.1%) 1/183 (0.5%) 1/63 (1.6%) 1/25 (4%)
    Retinal vein occlusion (Study eye) 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 1/25 (4%)
    Vision blurred (Study eye) 1/180 (0.6%) 6/183 (3.3%) 0/63 (0%) 0/25 (0%)
    Visual acuity reduced (Study eye) 5/180 (2.8%) 6/183 (3.3%) 4/63 (6.3%) 1/25 (4%)
    Vitreous adhesions (Study eye) 1/180 (0.6%) 2/183 (1.1%) 2/63 (3.2%) 0/25 (0%)
    Vitreous detachment (Study eye) 8/180 (4.4%) 7/183 (3.8%) 1/63 (1.6%) 0/25 (0%)
    Vitreous floaters (Study eye) 7/180 (3.9%) 10/183 (5.5%) 4/63 (6.3%) 1/25 (4%)
    Vitreous haemorrhage (Study eye) 5/180 (2.8%) 6/183 (3.3%) 1/63 (1.6%) 0/25 (0%)
    Gastrointestinal disorders
    Diarrhoea 5/180 (2.8%) 2/183 (1.1%) 3/63 (4.8%) 0/25 (0%)
    Gastrooesophageal reflux disease 1/180 (0.6%) 8/183 (4.4%) 0/63 (0%) 0/25 (0%)
    Gingival bleeding 0/180 (0%) 0/183 (0%) 0/63 (0%) 1/25 (4%)
    Nausea 2/180 (1.1%) 2/183 (1.1%) 2/63 (3.2%) 0/25 (0%)
    Toothache 0/180 (0%) 0/183 (0%) 2/63 (3.2%) 0/25 (0%)
    Vomiting 3/180 (1.7%) 2/183 (1.1%) 2/63 (3.2%) 0/25 (0%)
    General disorders
    Oedema peripheral 6/180 (3.3%) 2/183 (1.1%) 2/63 (3.2%) 0/25 (0%)
    Infections and infestations
    Acute sinusitis 0/180 (0%) 0/183 (0%) 0/63 (0%) 1/25 (4%)
    Bronchitis 3/180 (1.7%) 1/183 (0.5%) 1/63 (1.6%) 1/25 (4%)
    Conjunctivitis (Fellow untreated eye) 1/180 (0.6%) 5/183 (2.7%) 1/63 (1.6%) 0/25 (0%)
    Conjunctivitis (Study eye) 1/180 (0.6%) 4/183 (2.2%) 1/63 (1.6%) 0/25 (0%)
    Herpes zoster 2/180 (1.1%) 4/183 (2.2%) 1/63 (1.6%) 0/25 (0%)
    Influenza 13/180 (7.2%) 13/183 (7.1%) 2/63 (3.2%) 1/25 (4%)
    Laryngitis 2/180 (1.1%) 0/183 (0%) 1/63 (1.6%) 1/25 (4%)
    Nasopharyngitis 15/180 (8.3%) 17/183 (9.3%) 4/63 (6.3%) 1/25 (4%)
    Onychomycosis 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 1/25 (4%)
    Pneumonia 4/180 (2.2%) 2/183 (1.1%) 1/63 (1.6%) 0/25 (0%)
    Sinusitis 8/180 (4.4%) 2/183 (1.1%) 1/63 (1.6%) 0/25 (0%)
    Upper respiratory tract infection 6/180 (3.3%) 6/183 (3.3%) 3/63 (4.8%) 0/25 (0%)
    Urinary tract infection 6/180 (3.3%) 4/183 (2.2%) 3/63 (4.8%) 0/25 (0%)
    Injury, poisoning and procedural complications
    Contusion 1/180 (0.6%) 3/183 (1.6%) 1/63 (1.6%) 1/25 (4%)
    Fall 2/180 (1.1%) 6/183 (3.3%) 3/63 (4.8%) 0/25 (0%)
    Limb injury 1/180 (0.6%) 0/183 (0%) 0/63 (0%) 1/25 (4%)
    Procedural pain 4/180 (2.2%) 1/183 (0.5%) 0/63 (0%) 0/25 (0%)
    Upper limb fracture 0/180 (0%) 0/183 (0%) 0/63 (0%) 1/25 (4%)
    Investigations
    Blood pressure increased 3/180 (1.7%) 0/183 (0%) 0/63 (0%) 1/25 (4%)
    Intraocular pressure increased (Study eye) 17/180 (9.4%) 17/183 (9.3%) 2/63 (3.2%) 0/25 (0%)
    Metabolism and nutrition disorders
    Diabetes mellitus 3/180 (1.7%) 3/183 (1.6%) 2/63 (3.2%) 0/25 (0%)
    Hypercholesterolaemia 3/180 (1.7%) 6/183 (3.3%) 0/63 (0%) 0/25 (0%)
    Hyperlipidaemia 2/180 (1.1%) 0/183 (0%) 3/63 (4.8%) 0/25 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 4/180 (2.2%) 6/183 (3.3%) 1/63 (1.6%) 0/25 (0%)
    Arthritis 2/180 (1.1%) 2/183 (1.1%) 0/63 (0%) 1/25 (4%)
    Back pain 5/180 (2.8%) 8/183 (4.4%) 1/63 (1.6%) 2/25 (8%)
    Bone pain 0/180 (0%) 0/183 (0%) 0/63 (0%) 1/25 (4%)
    Musculoskeletal pain 1/180 (0.6%) 5/183 (2.7%) 1/63 (1.6%) 1/25 (4%)
    Osteoarthritis 5/180 (2.8%) 8/183 (4.4%) 3/63 (4.8%) 1/25 (4%)
    Pain in extremity 4/180 (2.2%) 7/183 (3.8%) 0/63 (0%) 0/25 (0%)
    Nervous system disorders
    Dizziness 2/180 (1.1%) 6/183 (3.3%) 0/63 (0%) 1/25 (4%)
    Headache 11/180 (6.1%) 9/183 (4.9%) 6/63 (9.5%) 0/25 (0%)
    Migraine 0/180 (0%) 4/183 (2.2%) 1/63 (1.6%) 0/25 (0%)
    Presyncope 0/180 (0%) 1/183 (0.5%) 0/63 (0%) 1/25 (4%)
    Sciatica 0/180 (0%) 0/183 (0%) 2/63 (3.2%) 0/25 (0%)
    Visual field defect (Fellow untreated eye) 0/180 (0%) 0/183 (0%) 0/63 (0%) 1/25 (4%)
    Psychiatric disorders
    Depression 1/180 (0.6%) 4/183 (2.2%) 1/63 (1.6%) 0/25 (0%)
    Insomnia 0/180 (0%) 4/183 (2.2%) 0/63 (0%) 0/25 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough 4/180 (2.2%) 6/183 (3.3%) 4/63 (6.3%) 0/25 (0%)
    Oropharyngeal pain 4/180 (2.2%) 2/183 (1.1%) 0/63 (0%) 0/25 (0%)
    Pleurisy 1/180 (0.6%) 0/183 (0%) 0/63 (0%) 1/25 (4%)
    Skin and subcutaneous tissue disorders
    Dermatitis allergic 1/180 (0.6%) 0/183 (0%) 2/63 (3.2%) 0/25 (0%)
    Vascular disorders
    Hypertension 19/180 (10.6%) 22/183 (12%) 7/63 (11.1%) 2/25 (8%)
    Phlebitis superficial 0/180 (0%) 0/183 (0%) 0/63 (0%) 1/25 (4%)

    Limitations/Caveats

    [Not Specified]

    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 (ie, data from all sites) in the clinical trial.

    Results Point of Contact

    Name/Title Clinical Disclosure Office
    Organization Novartis Pharmaceuticals
    Phone 862-778-8300
    Email
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01599650
    Other Study ID Numbers:
    • CRFB002E2402
    • 2011-002859-34
    First Posted:
    May 16, 2012
    Last Update Posted:
    Nov 10, 2016
    Last Verified:
    Sep 1, 2016