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Efficacy/Safety of Verteporfin Photodynamic Therapy and Ranibizumab Compared With Ranibizumab in Patients With Subfoveal Choroidal Neovascularization

Sponsor
Novartis (Industry)
Overall Status
Completed
CT.gov ID
NCT00436553
Collaborator
(none)
321
Enrollment
43
Locations
3
Arms
32
Duration (Months)
7.5
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study evaluated the effect of combination therapy with verteporfin photodynamic therapy and ranibizumab on visual acuity and anatomic outcomes compared to ranibizumab monotherapy and the durability of response observed in patients with choroidal neovascularization secondary to age-related macular degeneration.

Condition or Disease Intervention/Treatment Phase
  • Drug: Verteporfin Photodynamic Therapy
  • Drug: Ranibizumab
  • Drug: Verteporfin Placebo
  • Drug: Ranibizumab Placebo
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
321 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A 24-month Randomized, Double-masked, Controlled, Multicenter, Phase IIIB Study Assessing Safety and Efficacy of Verteporfin Photodynamic Therapy Administered in Conjunction With Ranibizumab Versus Ranibizumab Monotherapy in Patients With Subfoveal Choroidal Neovascularization Secondary to Age-related Macular Degeneration
Study Start Date :
Feb 1, 2007
Actual Primary Completion Date :
Oct 1, 2009
Actual Study Completion Date :
Oct 1, 2009

Arms and Interventions

Arm Intervention/Treatment
Experimental: Verteporfin With Standard Fluence Rate Plus Ranibizumab

Patients received three consecutive monthly ranibizumab injections on Day 1 and at Months 1 and 2, and thereafter as needed at intervals of at least 30 days based on retreatment criteria. These patients also received verteporfin photodynamic therapy (PDT) with standard fluence (SF) rate on Day 1 and then as needed from Month 3 at intervals of at least 90 days based on the retreatment criteria. From month 3 onward, retreatments were determined based on study-specific retreatment criteria that included retinal thickness by Optical Coherence Tomography (OCT), sub-retinal hemorrhage evaluated by ophthalmoscopic examination, visual acuity assessed using Early treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart and choroidal neovascularization (CNV) leakage assessed by fluorescein angiography (FA). Patients received sham intravitreal injections for the first 12 months if retreatment with ranibizumab was not warranted based on the retreatment criteria.

Drug: Verteporfin Photodynamic Therapy
After a 10-minute intravenous infusion of verteporfin at a dose of 6 mg/m^2 body surface area, verteporfin was activated by light application of 50 J/cm^2 (Standard Fluence rate) or 25 J/cm^2 (Reduced Fluence rate) to the study eye, begun 15 minutes after the start of the infusion.
Other Names:
  • Visudyne

    • Drug: Ranibizumab
    Ranibizumab 0.5 mg administered as an intravitreal injection.
    Other Names:
  • Lucentis

    • Drug: Ranibizumab Placebo
    To maintain masking, patients in the combination groups received sham intravitreal injections whenever retreatment with active Ranibizumab was not warranted based on the retreatment algorithm.
    Active Comparator: Ranibizumab Monotherapy

    Patients received monthly ranibizumab injections for 12 months and thereafter as needed based on the retreatment criteria. These patients were also administered verteporfin placebo infusion with sham PDT on Day 1 and then as needed from Month 3 at intervals of at least 90 days based on the retreatment criteria. Retreatments were determined based on study specific retreatment criteria that included retinal thickness by Optical Coherence Tomography (OCT), sub-retinal hemorrhage evaluated by ophthalmoscopic examination, visual acuity assessed using Early treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart and choroidal neovascularization (CNV) leakage assessed by fluorescein angiography (FA).

    Drug: Ranibizumab
    Ranibizumab 0.5 mg administered as an intravitreal injection.
    Other Names:
  • Lucentis

    • Drug: Verteporfin Placebo
    To maintain masking, as a placebo for verteporfin photodynamic therapy, patients were administered a 10-minute intravenous infusion of 5% dextrose solution, followed by light application of 50 J/cm^2 to the study eye, begun 15 minutes after the start of infusion.
    Experimental: Verteporfin With Reduced Fluence Rate Plus Ranibizumab

    Patients received three consecutive monthly ranibizumab injections on Day 1 and at Months 1 and 2, and thereafter as needed at intervals of at least 30 days based on retreatment criteria. These patients also received verteporfin PDT with reduced fluence (RF) rate on Day 1 and then as needed from Month 3 at intervals of at least 90 days based on the retreatment criteria. From month 3 onward, retreatments were determined based on study-specific retreatment criteria that included retinal thickness by Optical Coherence Tomography (OCT), sub-retinal hemorrhage evaluated by ophthalmoscopic examination, visual acuity assessed using Early treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart and choroidal neovascularization (CNV) leakage assessed by fluorescein angiography (FA). Patients received sham intravitreal injections for the first 12 months if retreatment with ranibizumab was not warranted based on the retreatment criteria.

    Drug: Verteporfin Photodynamic Therapy
    After a 10-minute intravenous infusion of verteporfin at a dose of 6 mg/m^2 body surface area, verteporfin was activated by light application of 50 J/cm^2 (Standard Fluence rate) or 25 J/cm^2 (Reduced Fluence rate) to the study eye, begun 15 minutes after the start of the infusion.
    Other Names:
  • Visudyne

    • Drug: Ranibizumab
    Ranibizumab 0.5 mg administered as an intravitreal injection.
    Other Names:
  • Lucentis

    • Drug: Ranibizumab Placebo
    To maintain masking, patients in the combination groups received sham intravitreal injections whenever retreatment with active Ranibizumab was not warranted based on the retreatment algorithm.

    Outcome Measures

    Primary Outcome Measures

    1. Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) of the Study Eye at Month 12 [Baseline and Month 12]

      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 ETDRS visual acuity score of 85 is approximately 20/20. An increase in the VA score indicates improvement in visual acuity.

    2. Percent of Patients With a Treatment-free Interval of at Least 3 Months Following the Month 2 Visit [Month 2 up to Month 11]

      The number of patients with a ranibizumab treatment-free interval, ie, no active ranibizumab treatments for at least 3 months duration (at least 2 consecutive monthly visits), anytime following the Month 2 ranibizumab treatment. Only active ranibizumab treatments were considered.

    Secondary Outcome Measures

    1. Change From Baseline in Total Area of Leakage of the Study Eye at Month 12 [Baseline and Month 12]

      Total area of leakage of the study eye was assessed at the Central Reading Center (CRC) using Fluorescein angiography (FA).

    2. Percentage of Patients With Fluorescein Leakage in the Study Eye at Month 12 [Month 12]

      The percentage of patients with leakage of the study eye was assessed at the Central Reading Center (CRC) using Fluorescein angiography (FA).

    3. Change From Baseline in Central Retinal Thickness at Month 12 [Baseline and Month 12]

      Optical coherence tomography was performed in the study eyes and the evaluations of the images were performed by the central reading center.

    Eligibility Criteria

    Criteria

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

    • Subjects of either gender age 50 years or older

    • Subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD)

    Exclusion Criteria:

    • Choroidal neovascularization due to causes other than AMD

    • Prior treatment for neovascular AMD in the study eye

    Other protocol-defined inclusion/exclusion criteria may apply

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Novartis Investigative Site Tucson Arizona United States 85704
    2 Novartis Investigative Site Beverly Hills California United States 90211
    3 Novartis Investigative Site Oakland California United States 94609
    4 Novartis Investigative Site Pasadena California United States 91105-3153
    5 Novartis Investigative Site Sacramento California United States 95819
    6 West Coast Retina Medical Group Inc. - 185 Berry St. Suite 130 San Francisco California United States 94107
    7 Novartis Investigative Site Santa Ana California United States 92705
    8 Novartis Investigative Site Denver Colorado United States 80210
    9 Novartis Investigative Site Aiea Hawaii United States 96701
    10 Novartis Investigative Site Iowa City Iowa United States 52242
    11 Novartis Investigative Site Wichita Kansas United States 67214
    12 Novartis Investigative Site Lexington Kentucky United States 40509
    13 Novartis Investigative Site Paducah Kentucky United States 42001
    14 Novartis Investigative Site Baltimore Maryland United States 21205
    15 Novartis Investigative Site Grand Rapids Michigan United States 49252
    16 Novartis Investigative SIte Royal Oak Michigan United States 48073
    17 Novartis Investigative Site Williamsburg Michigan United States 49690
    18 Novartis Investigative Site Independence Missouri United States 64055
    19 Novartis Investigative Site St. Louis Missouri United States 63110
    20 Novartis Investigative Site Toms River New Jersey United States 08755
    21 Novartis Investigative Site Lynbrook New York United States 11563
    22 Novartis Investigative Site Rochester New York United States 14620
    23 Novartis Investigative Site Beachwood Ohio United States 44122
    24 Novartis Investigative Site Cincinnati Ohio United States 45242
    25 Novartis Investigative Site Cleveland Ohio United States 44195
    26 Novartis Investigative Site Pittsburgh Pennsylvania United States 15213
    27 Novartis Investigative Site West Mifflin Pennsylvania United States 15122
    28 Novartis Investigative Site West Columbia South Carolina United States 29169
    29 Novartis Investigative Site Rapid City South Dakota United States 57701
    30 Novartis Investigative Site Kingsport Tennessee United States 37660
    31 Novartis Investigative Site Knoxville Tennessee United States 37909
    32 Novartis Investigative Site Austin Texas United States 78705
    33 Novartis Investigative Site Houston Texas United States 77030
    34 Novartis Investigative Site Fairfax Virginia United States 22031
    35 Novartis Investigative Site Richmond Virginia United States 23226
    36 Novartis Investigative Site Milwaukee Wisconsin United States 53226
    37 Novartis Investigative Site Edmonton Alberta Canada T5H OX5
    38 Novartis Investigative Site Vancouver British Columbia Canada V5Z 3N9
    39 Novartis Investigative Site Halifax Nova Scotia Canada B3H 2Y6
    40 Ivey Eye Institute, Dr. Thomas Sheidow London Ontario Canada N6A 4G5
    41 Novartis Investigative Site London Ontario Canada N6A 4G5
    42 Novartis Investigative Site Ottawa Ontario Canada KIH 8L6
    43 Novartis Investigative Site Montreal Quebec Canada H2L 4MI

    Sponsors and Collaborators

    • Novartis

    Investigators

    • Study Chair: Novartis, Novartis

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00436553
    Other Study ID Numbers:
    • CBPD952A2308
    First Posted:
    Feb 19, 2007
    Last Update Posted:
    Apr 19, 2011
    Last Verified:
    Mar 1, 2011
    Keywords provided by , ,
    Age-related macular degeneration; AMD
    choroidal neovascularization
    verteporfin
    ranibizumab
    Additional relevant MeSH terms:
    Macular Degeneration
    Choroidal Neovascularization
    Neovascularization, Pathologic
    Ranibizumab
    Verteporfin

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Verteporfin SF + Ranibizumab Verteporfin RF + Ranibizumab Ranibizumab Monotherapy
    Arm/Group Description Patients received three consecutive monthly ranibizumab injections on Day 1 and at Months 1 and 2, and thereafter as needed at intervals of at least 30 days based on retreatment criteria. These patients also received verteporfin photodynamic therapy (PDT) with standard fluence (SF) rate on Day 1 and then as needed from Month 3 at intervals of at least 90 days based on the retreatment criteria. From month 3 onward, retreatments were determined based on study-specific retreatment criteria that included retinal thickness by Optical Coherence Tomography (OCT), sub-retinal hemorrhage evaluated by ophthalmoscopic examination, visual acuity assessed using Early treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart and choroidal neovascularization (CNV) leakage assessed by fluorescein angiography (FA). Patients received sham intravitreal injections for the first 12 months if retreatment with ranibizumab was not warranted based on the retreatment criteria. Patients received three consecutive monthly ranibizumab injections on Day 1 and at Months 1 and 2, and thereafter as needed at intervals of at least 30 days based on retreatment criteria. These patients also received verteporfin PDT with reduced fluence (RF) rate on Day 1 and then as needed from Month 3 at intervals of at least 90 days based on the retreatment criteria. From month 3 onward, retreatments were determined based on study-specific retreatment criteria that included retinal thickness by Optical Coherence Tomography (OCT), sub-retinal hemorrhage evaluated by ophthalmoscopic examination, visual acuity assessed using Early treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart and choroidal neovascularization (CNV) leakage assessed by fluorescein angiography (FA). Patients received sham intravitreal injections for the first 12 months if retreatment with ranibizumab was not warranted based on the retreatment criteria. Patients received monthly ranibizumab injections for 12 months and thereafter as needed based on the retreatment criteria. These patients were also administered verteporfin placebo infusion with sham PDT on Day 1 and then as needed from Month 3 at intervals of at least 90 days based on the retreatment criteria. Retreatments were determined based on study specific retreatment criteria that included retinal thickness by Optical Coherence Tomography (OCT), sub-retinal hemorrhage evaluated by ophthalmoscopic examination, visual acuity assessed using Early treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart and choroidal neovascularization (CNV) leakage assessed by fluorescein angiography (FA).
    Period Title: Overall Study
    STARTED 104 105 112
    COMPLETED 91 93 102
    NOT COMPLETED 13 12 10

    Baseline Characteristics

    Arm/Group Title Verteporfin SF + Ranibizumab Verteporfin RF + Ranibizumab Ranibizumab Monotherapy Total
    Arm/Group Description Patients received three consecutive monthly ranibizumab injections on Day 1 and at Months 1 and 2, and thereafter as needed at intervals of at least 30 days based on retreatment criteria. These patients also received verteporfin photodynamic therapy (PDT) with standard fluence (SF) rate on Day 1 and then as needed from Month 3 at intervals of at least 90 days based on the retreatment criteria. From month 3 onward, retreatments were determined based on study-specific retreatment criteria that included retinal thickness by Optical Coherence Tomography (OCT), sub-retinal hemorrhage evaluated by ophthalmoscopic examination, visual acuity assessed using Early treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart and choroidal neovascularization (CNV) leakage assessed by fluorescein angiography (FA). Patients received sham intravitreal injections for the first 12 months if retreatment with ranibizumab was not warranted based on the retreatment criteria. Patients received three consecutive monthly ranibizumab injections on Day 1 and at Months 1 and 2, and thereafter as needed at intervals of at least 30 days based on retreatment criteria. These patients also received verteporfin PDT with reduced fluence (RF) rate on Day 1 and then as needed from Month 3 at intervals of at least 90 days based on the retreatment criteria. From month 3 onward, retreatments were determined based on study-specific retreatment criteria that included retinal thickness by Optical Coherence Tomography (OCT), sub-retinal hemorrhage evaluated by ophthalmoscopic examination, visual acuity assessed using Early treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart and choroidal neovascularization (CNV) leakage assessed by fluorescein angiography (FA). Patients received sham intravitreal injections for the first 12 months if retreatment with ranibizumab was not warranted based on the retreatment criteria. Patients received monthly ranibizumab injections for 12 months and thereafter as needed based on the retreatment criteria. These patients were also administered verteporfin placebo infusion with sham PDT on Day 1 and then as needed from Month 3 at intervals of at least 90 days based on the retreatment criteria. Retreatments were determined based on study specific retreatment criteria that included retinal thickness by Optical Coherence Tomography (OCT), sub-retinal hemorrhage evaluated by ophthalmoscopic examination, visual acuity assessed using Early treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart and choroidal neovascularization (CNV) leakage assessed by fluorescein angiography (FA). Total of all reporting groups
    Overall Participants 104 105 112 321
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    77.5
    (8.42)
    77.4
    (8.48)
    77.2
    (7.97)
    77.3
    (8.26)
    Sex: Female, Male (Count of Participants)
    Female
    64
    61.5%
    53
    50.5%
    75
    67%
    192
    59.8%
    Male
    40
    38.5%
    52
    49.5%
    37
    33%
    129
    40.2%

    Outcome Measures

    1. Primary Outcome
    Title Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) of the Study Eye at Month 12
    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 ETDRS visual acuity score of 85 is approximately 20/20. An increase in the VA score indicates improvement in visual acuity.
    Time Frame Baseline and Month 12

    Outcome Measure Data

    Analysis Population Description
    The Full analysis set (FAS) consisting of all randomized patients that received at least one application of study drug and had at least one post-baseline assessment for BCVA in the study eye. Last observation carried forward (LOCF) was utilized.
    Arm/Group Title Verteporfin SF + Ranibizumab Verteporfin RF + Ranibizumab Ranibizumab Monotherapy
    Arm/Group Description Patients received three consecutive monthly ranibizumab injections on Day 1 and at Months 1 and 2, and thereafter as needed at intervals of at least 30 days based on retreatment criteria. These patients also received verteporfin photodynamic therapy (PDT) with standard fluence (SF) rate on Day 1 and then as needed from Month 3 at intervals of at least 90 days based on the retreatment criteria. From month 3 onward, retreatments were determined based on study-specific retreatment criteria that included retinal thickness by Optical Coherence Tomography (OCT), sub-retinal hemorrhage evaluated by ophthalmoscopic examination, visual acuity assessed using Early treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart and choroidal neovascularization (CNV) leakage assessed by fluorescein angiography (FA). Patients received sham intravitreal injections for the first 12 months if retreatment with ranibizumab was not warranted based on the retreatment criteria. Patients received three consecutive monthly ranibizumab injections on Day 1 and at Months 1 and 2, and thereafter as needed at intervals of at least 30 days based on retreatment criteria. These patients also received verteporfin PDT with reduced fluence (RF) rate on Day 1 and then as needed from Month 3 at intervals of at least 90 days based on the retreatment criteria. From month 3 onward, retreatments were determined based on study-specific retreatment criteria that included retinal thickness by Optical Coherence Tomography (OCT), sub-retinal hemorrhage evaluated by ophthalmoscopic examination, visual acuity assessed using Early treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart and choroidal neovascularization (CNV) leakage assessed by fluorescein angiography (FA). Patients received sham intravitreal injections for the first 12 months if retreatment with ranibizumab was not warranted based on the retreatment criteria. Patients received monthly ranibizumab injections for 12 months and thereafter as needed based on the retreatment criteria. These patients were also administered verteporfin placebo infusion with sham PDT on Day 1 and then as needed from Month 3 at intervals of at least 90 days based on the retreatment criteria. Retreatments were determined based on study specific retreatment criteria that included retinal thickness by Optical Coherence Tomography (OCT), sub-retinal hemorrhage evaluated by ophthalmoscopic examination, visual acuity assessed using Early treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart and choroidal neovascularization (CNV) leakage assessed by fluorescein angiography (FA).
    Measure Participants 103 104 110
    Baseline
    53.7
    (13.52)
    54.6
    (12.78)
    54.8
    (13.55)
    Month 12
    59.0
    (17.47)
    59.0
    (18.03)
    63.0
    (18.88)
    Change from baseline
    5.3
    (15.66)
    4.4
    (15.47)
    8.1
    (15.09)
    2. Secondary Outcome
    Title Change From Baseline in Total Area of Leakage of the Study Eye at Month 12
    Description Total area of leakage of the study eye was assessed at the Central Reading Center (CRC) using Fluorescein angiography (FA).
    Time Frame Baseline and Month 12

    Outcome Measure Data

    Analysis Population Description
    Full analysis set (FAS), observed data.
    Arm/Group Title Verteporfin SF + Ranibizumab Verteporfin RF + Ranibizumab Ranibizumab Monotherapy
    Arm/Group Description Patients received three consecutive monthly ranibizumab injections on Day 1 and at Months 1 and 2, and thereafter as needed at intervals of at least 30 days based on retreatment criteria. These patients also received verteporfin photodynamic therapy (PDT) with standard fluence (SF) rate on Day 1 and then as needed from Month 3 at intervals of at least 90 days based on the retreatment criteria. From month 3 onward, retreatments were determined based on study-specific retreatment criteria that included retinal thickness by Optical Coherence Tomography (OCT), sub-retinal hemorrhage evaluated by ophthalmoscopic examination, visual acuity assessed using Early treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart and choroidal neovascularization (CNV) leakage assessed by fluorescein angiography (FA). Patients received sham intravitreal injections for the first 12 months if retreatment with ranibizumab was not warranted based on the retreatment criteria. Patients received three consecutive monthly ranibizumab injections on Day 1 and at Months 1 and 2, and thereafter as needed at intervals of at least 30 days based on retreatment criteria. These patients also received verteporfin PDT with reduced fluence (RF) rate on Day 1 and then as needed from Month 3 at intervals of at least 90 days based on the retreatment criteria. From month 3 onward, retreatments were determined based on study-specific retreatment criteria that included retinal thickness by Optical Coherence Tomography (OCT), sub-retinal hemorrhage evaluated by ophthalmoscopic examination, visual acuity assessed using Early treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart and choroidal neovascularization (CNV) leakage assessed by fluorescein angiography (FA). Patients received sham intravitreal injections for the first 12 months if retreatment with ranibizumab was not warranted based on the retreatment criteria. Patients received monthly ranibizumab injections for 12 months and thereafter as needed based on the retreatment criteria. These patients were also administered verteporfin placebo infusion with sham PDT on Day 1 and then as needed from Month 3 at intervals of at least 90 days based on the retreatment criteria. Retreatments were determined based on study specific retreatment criteria that included retinal thickness by Optical Coherence Tomography (OCT), sub-retinal hemorrhage evaluated by ophthalmoscopic examination, visual acuity assessed using Early treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart and choroidal neovascularization (CNV) leakage assessed by fluorescein angiography (FA).
    Measure Participants 67 66 78
    Baseline
    6.654
    (4.0956)
    6.211
    (5.0618)
    6.931
    (4.6473)
    Month 12
    3.472
    (4.2340)
    3.024
    (4.0188)
    3.177
    (4.9930)
    Change from Baseline
    -3.182
    (4.9729)
    -3.187
    (5.9744)
    -3.753
    (5.8005)
    3. Secondary Outcome
    Title Percentage of Patients With Fluorescein Leakage in the Study Eye at Month 12
    Description The percentage of patients with leakage of the study eye was assessed at the Central Reading Center (CRC) using Fluorescein angiography (FA).
    Time Frame Month 12

    Outcome Measure Data

    Analysis Population Description
    Full analysis set (FAS), observed data.
    Arm/Group Title Verteporfin SF + Ranibizumab Verteporfin RF + Ranibizumab Ranibizumab Monotherapy
    Arm/Group Description Patients received three consecutive monthly ranibizumab injections on Day 1 and at Months 1 and 2, and thereafter as needed at intervals of at least 30 days based on retreatment criteria. These patients also received verteporfin photodynamic therapy (PDT) with standard fluence (SF) rate on Day 1 and then as needed from Month 3 at intervals of at least 90 days based on the retreatment criteria. From month 3 onward, retreatments were determined based on study-specific retreatment criteria that included retinal thickness by Optical Coherence Tomography (OCT), sub-retinal hemorrhage evaluated by ophthalmoscopic examination, visual acuity assessed using Early treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart and choroidal neovascularization (CNV) leakage assessed by fluorescein angiography (FA). Patients received sham intravitreal injections for the first 12 months if retreatment with ranibizumab was not warranted based on the retreatment criteria. Patients received three consecutive monthly ranibizumab injections on Day 1 and at Months 1 and 2, and thereafter as needed at intervals of at least 30 days based on retreatment criteria. These patients also received verteporfin PDT with reduced fluence (RF) rate on Day 1 and then as needed from Month 3 at intervals of at least 90 days based on the retreatment criteria. From month 3 onward, retreatments were determined based on study-specific retreatment criteria that included retinal thickness by Optical Coherence Tomography (OCT), sub-retinal hemorrhage evaluated by ophthalmoscopic examination, visual acuity assessed using Early treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart and choroidal neovascularization (CNV) leakage assessed by fluorescein angiography (FA). Patients received sham intravitreal injections for the first 12 months if retreatment with ranibizumab was not warranted based on the retreatment criteria. Patients received monthly ranibizumab injections for 12 months and thereafter as needed based on the retreatment criteria. These patients were also administered verteporfin placebo infusion with sham PDT on Day 1 and then as needed from Month 3 at intervals of at least 90 days based on the retreatment criteria. Retreatments were determined based on study specific retreatment criteria that included retinal thickness by Optical Coherence Tomography (OCT), sub-retinal hemorrhage evaluated by ophthalmoscopic examination, visual acuity assessed using Early treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart and choroidal neovascularization (CNV) leakage assessed by fluorescein angiography (FA).
    Measure Participants 67 66 79
    Number [Percentage of participants]
    58.2
    (0) 56%
    54.5
    (0) 51.9%
    41.8
    (0) 37.3%
    4. Secondary Outcome
    Title Change From Baseline in Central Retinal Thickness at Month 12
    Description Optical coherence tomography was performed in the study eyes and the evaluations of the images were performed by the central reading center.
    Time Frame Baseline and Month 12

    Outcome Measure Data

    Analysis Population Description
    Full analysis set (FAS), observed data.
    Arm/Group Title Verteporfin SF + Ranibizumab Verteporfin RF + Ranibizumab Ranibizumab Monotherapy
    Arm/Group Description Patients received three consecutive monthly ranibizumab injections on Day 1 and at Months 1 and 2, and thereafter as needed at intervals of at least 30 days based on retreatment criteria. These patients also received verteporfin photodynamic therapy (PDT) with standard fluence (SF) rate on Day 1 and then as needed from Month 3 at intervals of at least 90 days based on the retreatment criteria. From month 3 onward, retreatments were determined based on study-specific retreatment criteria that included retinal thickness by Optical Coherence Tomography (OCT), sub-retinal hemorrhage evaluated by ophthalmoscopic examination, visual acuity assessed using Early treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart and choroidal neovascularization (CNV) leakage assessed by fluorescein angiography (FA). Patients received sham intravitreal injections for the first 12 months if retreatment with ranibizumab was not warranted based on the retreatment criteria. Patients received three consecutive monthly ranibizumab injections on Day 1 and at Months 1 and 2, and thereafter as needed at intervals of at least 30 days based on retreatment criteria. These patients also received verteporfin PDT with reduced fluence (RF) rate on Day 1 and then as needed from Month 3 at intervals of at least 90 days based on the retreatment criteria. From month 3 onward, retreatments were determined based on study-specific retreatment criteria that included retinal thickness by Optical Coherence Tomography (OCT), sub-retinal hemorrhage evaluated by ophthalmoscopic examination, visual acuity assessed using Early treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart and choroidal neovascularization (CNV) leakage assessed by fluorescein angiography (FA). Patients received sham intravitreal injections for the first 12 months if retreatment with ranibizumab was not warranted based on the retreatment criteria. Patients received monthly ranibizumab injections for 12 months and thereafter as needed based on the retreatment criteria. These patients were also administered verteporfin placebo infusion with sham PDT on Day 1 and then as needed from Month 3 at intervals of at least 90 days based on the retreatment criteria. Retreatments were determined based on study specific retreatment criteria that included retinal thickness by Optical Coherence Tomography (OCT), sub-retinal hemorrhage evaluated by ophthalmoscopic examination, visual acuity assessed using Early treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart and choroidal neovascularization (CNV) leakage assessed by fluorescein angiography (FA).
    Measure Participants 76 80 89
    Baseline
    444.654
    (137.7119)
    446.638
    (129.5482)
    456.824
    (153.4270)
    Month 12
    292.921
    (79.2733)
    305.719
    (80.4508)
    284.586
    (75.4892)
    Change from Baseline
    -151.733
    (135.6200)
    -140.919
    (128.0741)
    -172.238
    (166.6691)
    5. Primary Outcome
    Title Percent of Patients With a Treatment-free Interval of at Least 3 Months Following the Month 2 Visit
    Description The number of patients with a ranibizumab treatment-free interval, ie, no active ranibizumab treatments for at least 3 months duration (at least 2 consecutive monthly visits), anytime following the Month 2 ranibizumab treatment. Only active ranibizumab treatments were considered.
    Time Frame Month 2 up to Month 11

    Outcome Measure Data

    Analysis Population Description
    Full analysis set (FAS) - Only the combination groups were analyzed. The percent of subjects with a ranibizumab treatment-free interval of at least 3 months duration following the Month 2 ranibizumab treatment was calculated using the subjects still in the study at Month 5.
    Arm/Group Title Verteporfin SF + Ranibizumab Verteporfin RF + Ranibizumab
    Arm/Group Description Patients received three consecutive monthly ranibizumab injections on Day 1 and at Months 1 and 2, and thereafter as needed at intervals of at least 30 days based on retreatment criteria. These patients also received verteporfin photodynamic therapy (PDT) with standard fluence (SF) rate on Day 1 and then as needed from Month 3 at intervals of at least 90 days based on the retreatment criteria. From month 3 onward, retreatments were determined based on study-specific retreatment criteria that included retinal thickness by Optical Coherence Tomography (OCT), sub-retinal hemorrhage evaluated by ophthalmoscopic examination, visual acuity assessed using Early treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart and choroidal neovascularization (CNV) leakage assessed by fluorescein angiography (FA). Patients received sham intravitreal injections for the first 12 months if retreatment with ranibizumab was not warranted based on the retreatment criteria. Patients received three consecutive monthly ranibizumab injections on Day 1 and at Months 1 and 2, and thereafter as needed at intervals of at least 30 days based on retreatment criteria. These patients also received verteporfin PDT with reduced fluence (RF) rate on Day 1 and then as needed from Month 3 at intervals of at least 90 days based on the retreatment criteria. From month 3 onward, retreatments were determined based on study-specific retreatment criteria that included retinal thickness by Optical Coherence Tomography (OCT), sub-retinal hemorrhage evaluated by ophthalmoscopic examination, visual acuity assessed using Early treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart and choroidal neovascularization (CNV) leakage assessed by fluorescein angiography (FA). Patients received sham intravitreal injections for the first 12 months if retreatment with ranibizumab was not warranted based on the retreatment criteria.
    Measure Participants 95 97
    Number [Percent of participants]
    92.6
    89%
    83.5
    79.5%

    Adverse Events

    Time Frame Cumulative up to Month 24
    Adverse Event Reporting Description The Safety set consisted of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. One patient was not treated as randomized. The safety data set includes patients as they were treated.
    Arm/Group Title Verteporfin SF + Ranibizumab Verteporfin RF + Ranibizumab Ranibizumab Monotherapy
    Arm/Group Description Patients received three consecutive monthly ranibizumab injections on Day 1 and at Months 1 and 2, and thereafter as needed at intervals of at least 30 days based on retreatment criteria. These patients also received verteporfin photodynamic therapy (PDT) with standard fluence (SF) rate on Day 1 and then as needed from Month 3 at intervals of at least 90 days based on the retreatment criteria. From month 3 onward, retreatments were determined based on study-specific retreatment criteria that included retinal thickness by Optical Coherence Tomography (OCT), sub-retinal hemorrhage evaluated by ophthalmoscopic examination, visual acuity assessed using Early treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart and choroidal neovascularization (CNV) leakage assessed by fluorescein angiography (FA). Patients received sham intravitreal injections for the first 12 months if retreatment with ranibizumab was not warranted based on the retreatment criteria. Patients received three consecutive monthly ranibizumab injections on Day 1 and at Months 1 and 2, and thereafter as needed at intervals of at least 30 days based on retreatment criteria. These patients also received verteporfin PDT with reduced fluence (RF) rate on Day 1 and then as needed from Month 3 at intervals of at least 90 days based on the retreatment criteria. From month 3 onward, retreatments were determined based on study-specific retreatment criteria that included retinal thickness by Optical Coherence Tomography (OCT), sub-retinal hemorrhage evaluated by ophthalmoscopic examination, visual acuity assessed using Early treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart and choroidal neovascularization (CNV) leakage assessed by fluorescein angiography (FA). Patients received sham intravitreal injections for the first 12 months if retreatment with ranibizumab was not warranted based on the retreatment criteria. Patients received monthly ranibizumab injections for 12 months and thereafter as needed based on the retreatment criteria. These patients were also administered verteporfin placebo infusion with sham PDT on Day 1 and then as needed from Month 3 at intervals of at least 90 days based on the retreatment criteria. Retreatments were determined based on study specific retreatment criteria that included retinal thickness by Optical Coherence Tomography (OCT), sub-retinal hemorrhage evaluated by ophthalmoscopic examination, visual acuity assessed using Early treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart and choroidal neovascularization (CNV) leakage assessed by fluorescein angiography (FA).
    All Cause Mortality
    Verteporfin SF + Ranibizumab Verteporfin RF + Ranibizumab Ranibizumab Monotherapy
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Verteporfin SF + Ranibizumab Verteporfin RF + Ranibizumab Ranibizumab Monotherapy
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 32/104 (30.8%) 29/106 (27.4%) 41/111 (36.9%)
    Blood and lymphatic system disorders
    Anaemia 1/104 (1%) 0/106 (0%) 0/111 (0%)
    Cardiac disorders
    Acute myocardial infarction 0/104 (0%) 1/106 (0.9%) 1/111 (0.9%)
    Angina pectoris 0/104 (0%) 1/106 (0.9%) 0/111 (0%)
    Atrial fibrillation 2/104 (1.9%) 0/106 (0%) 1/111 (0.9%)
    Bradycardia 0/104 (0%) 0/106 (0%) 3/111 (2.7%)
    Cardiac failure 0/104 (0%) 0/106 (0%) 1/111 (0.9%)
    Cardiac failure congestive 2/104 (1.9%) 2/106 (1.9%) 6/111 (5.4%)
    Cardio-respiratory arrest 0/104 (0%) 1/106 (0.9%) 0/111 (0%)
    Coronary artery disease 1/104 (1%) 1/106 (0.9%) 0/111 (0%)
    Myocardial infarction 1/104 (1%) 2/106 (1.9%) 1/111 (0.9%)
    Sick sinus syndrome 1/104 (1%) 0/106 (0%) 1/111 (0.9%)
    Tachycardia 1/104 (1%) 0/106 (0%) 0/111 (0%)
    Eye disorders
    Choroidal infarction (Study eye) 1/104 (1%) 0/106 (0%) 0/111 (0%)
    Eye pain (Study eye) 0/104 (0%) 0/106 (0%) 1/111 (0.9%)
    Macular hole (Study eye) 1/104 (1%) 0/106 (0%) 0/111 (0%)
    Macular oedema (Study eye) 1/104 (1%) 0/106 (0%) 0/111 (0%)
    Retinal artery occlusion (Fellow eye) 0/104 (0%) 0/106 (0%) 1/111 (0.9%)
    Retinal artery occlusion (Study eye) 0/104 (0%) 0/106 (0%) 1/111 (0.9%)
    Retinal haemorrhage (Study eye) 0/104 (0%) 0/106 (0%) 1/111 (0.9%)
    Visual acuity reduced (Study eye) 4/104 (3.8%) 1/106 (0.9%) 3/111 (2.7%)
    Gastrointestinal disorders
    Abdominal adhesions 1/104 (1%) 0/106 (0%) 0/111 (0%)
    Abdominal hernia 0/104 (0%) 0/106 (0%) 2/111 (1.8%)
    Colitis ischaemic 0/104 (0%) 1/106 (0.9%) 1/111 (0.9%)
    Diarrhoea 0/104 (0%) 1/106 (0.9%) 0/111 (0%)
    Enteritis 0/104 (0%) 1/106 (0.9%) 0/111 (0%)
    Gastritis 0/104 (0%) 1/106 (0.9%) 0/111 (0%)
    Inguinal hernia 0/104 (0%) 0/106 (0%) 1/111 (0.9%)
    Intestinal infarction 1/104 (1%) 0/106 (0%) 0/111 (0%)
    Intestinal obstruction 0/104 (0%) 0/106 (0%) 1/111 (0.9%)
    Oesophagitis 1/104 (1%) 0/106 (0%) 0/111 (0%)
    Pancreatitis 0/104 (0%) 1/106 (0.9%) 0/111 (0%)
    Peptic ulcer 0/104 (0%) 0/106 (0%) 1/111 (0.9%)
    Vomiting 1/104 (1%) 0/106 (0%) 0/111 (0%)
    General disorders
    Asthenia 2/104 (1.9%) 0/106 (0%) 0/111 (0%)
    Chest pain 0/104 (0%) 1/106 (0.9%) 0/111 (0%)
    Pyrexia 1/104 (1%) 0/106 (0%) 0/111 (0%)
    Hepatobiliary disorders
    Bile duct stone 1/104 (1%) 0/106 (0%) 0/111 (0%)
    Cholecystitis 1/104 (1%) 0/106 (0%) 0/111 (0%)
    Cholelithiasis 1/104 (1%) 0/106 (0%) 0/111 (0%)
    Immune system disorders
    Iodine allergy 0/104 (0%) 1/106 (0.9%) 0/111 (0%)
    Infections and infestations
    Breast cellulitis 1/104 (1%) 0/106 (0%) 0/111 (0%)
    Bronchitis 0/104 (0%) 0/106 (0%) 1/111 (0.9%)
    Cellulitis 0/104 (0%) 0/106 (0%) 1/111 (0.9%)
    Diverticulitis 0/104 (0%) 0/106 (0%) 1/111 (0.9%)
    Endophthalmitis (Study eye) 1/104 (1%) 0/106 (0%) 2/111 (1.8%)
    Gangrene 0/104 (0%) 0/106 (0%) 1/111 (0.9%)
    Gastroenteritis 0/104 (0%) 0/106 (0%) 2/111 (1.8%)
    Labyrinthitis 1/104 (1%) 0/106 (0%) 0/111 (0%)
    Lobar pneumonia 1/104 (1%) 0/106 (0%) 0/111 (0%)
    Pneumococcal sepsis 1/104 (1%) 0/106 (0%) 0/111 (0%)
    Pneumonia 2/104 (1.9%) 3/106 (2.8%) 4/111 (3.6%)
    Sepsis 0/104 (0%) 1/106 (0.9%) 0/111 (0%)
    Urinary tract infection 0/104 (0%) 1/106 (0.9%) 0/111 (0%)
    Injury, poisoning and procedural complications
    Fall 0/104 (0%) 0/106 (0%) 1/111 (0.9%)
    Femur fracture 0/104 (0%) 0/106 (0%) 1/111 (0.9%)
    Hip fracture 2/104 (1.9%) 1/106 (0.9%) 1/111 (0.9%)
    Implantable defibrillator malfunction 0/104 (0%) 0/106 (0%) 1/111 (0.9%)
    Joint sprain 0/104 (0%) 1/106 (0.9%) 0/111 (0%)
    Pacemaker complication 1/104 (1%) 0/106 (0%) 0/111 (0%)
    Rib fracture 0/104 (0%) 0/106 (0%) 1/111 (0.9%)
    Spinal compression fracture 1/104 (1%) 0/106 (0%) 0/111 (0%)
    Stress fracture 0/104 (0%) 1/106 (0.9%) 0/111 (0%)
    Traumatic brain injury 0/104 (0%) 0/106 (0%) 1/111 (0.9%)
    Investigations
    Weight decreased 0/104 (0%) 0/106 (0%) 1/111 (0.9%)
    Metabolism and nutrition disorders
    Decreased appetite 0/104 (0%) 0/106 (0%) 1/111 (0.9%)
    Dehydration 0/104 (0%) 1/106 (0.9%) 0/111 (0%)
    Hyponatraemia 1/104 (1%) 0/106 (0%) 0/111 (0%)
    Musculoskeletal and connective tissue disorders
    Arthritis 0/104 (0%) 0/106 (0%) 2/111 (1.8%)
    Intervertebral disc displacement 1/104 (1%) 0/106 (0%) 0/111 (0%)
    Osteoarthritis 1/104 (1%) 0/106 (0%) 0/111 (0%)
    Spinal column stenosis 1/104 (1%) 0/106 (0%) 0/111 (0%)
    Spondylolisthesis 0/104 (0%) 0/106 (0%) 1/111 (0.9%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Bile duct cancer 0/104 (0%) 0/106 (0%) 1/111 (0.9%)
    Bladder neoplasm 0/104 (0%) 1/106 (0.9%) 0/111 (0%)
    Brain neoplasm malignant 0/104 (0%) 1/106 (0.9%) 0/111 (0%)
    Breast cancer female 0/104 (0%) 1/106 (0.9%) 0/111 (0%)
    Breast cancer metastatic 0/104 (0%) 0/106 (0%) 1/111 (0.9%)
    Colorectal cancer recurrent 1/104 (1%) 0/106 (0%) 0/111 (0%)
    Lung neoplasm malignant 0/104 (0%) 2/106 (1.9%) 1/111 (0.9%)
    Lymphoma 0/104 (0%) 0/106 (0%) 1/111 (0.9%)
    Malignant melanoma 1/104 (1%) 1/106 (0.9%) 0/111 (0%)
    Metastases to bone 0/104 (0%) 0/106 (0%) 1/111 (0.9%)
    Metastases to lung 0/104 (0%) 0/106 (0%) 1/111 (0.9%)
    Multiple myeloma 1/104 (1%) 0/106 (0%) 0/111 (0%)
    Oesophageal carcinoma 0/104 (0%) 0/106 (0%) 1/111 (0.9%)
    Squamous cell carcinoma of skin 0/104 (0%) 0/106 (0%) 1/111 (0.9%)
    Transitional cell carcinoma 0/104 (0%) 1/106 (0.9%) 0/111 (0%)
    Ureteral neoplasm 0/104 (0%) 0/106 (0%) 1/111 (0.9%)
    Nervous system disorders
    Basal ganglia infarction 0/104 (0%) 0/106 (0%) 1/111 (0.9%)
    Cerebrovascular accident 1/104 (1%) 1/106 (0.9%) 1/111 (0.9%)
    Intracranial aneurysm 0/104 (0%) 1/106 (0.9%) 0/111 (0%)
    Myasthenia gravis 0/104 (0%) 0/106 (0%) 1/111 (0.9%)
    Presyncope 0/104 (0%) 0/106 (0%) 1/111 (0.9%)
    Syncope 0/104 (0%) 1/106 (0.9%) 0/111 (0%)
    Transient ischaemic attack 0/104 (0%) 1/106 (0.9%) 3/111 (2.7%)
    Psychiatric disorders
    Alcoholism 0/104 (0%) 1/106 (0.9%) 0/111 (0%)
    Completed suicide 1/104 (1%) 0/106 (0%) 0/111 (0%)
    Depression 0/104 (0%) 0/106 (0%) 1/111 (0.9%)
    Renal and urinary disorders
    Haematuria 1/104 (1%) 1/106 (0.9%) 0/111 (0%)
    Renal failure 0/104 (0%) 1/106 (0.9%) 1/111 (0.9%)
    Renal failure acute 0/104 (0%) 2/106 (1.9%) 1/111 (0.9%)
    Urinary retention 1/104 (1%) 0/106 (0%) 0/111 (0%)
    Reproductive system and breast disorders
    Benign prostatic hyperplasia 0/104 (0%) 1/106 (0.9%) 0/111 (0%)
    Respiratory, thoracic and mediastinal disorders
    Asthma 0/104 (0%) 1/106 (0.9%) 1/111 (0.9%)
    Chronic obstructive pulmonary disease 1/104 (1%) 1/106 (0.9%) 0/111 (0%)
    Dyspnoea 1/104 (1%) 1/106 (0.9%) 0/111 (0%)
    Pleurisy 0/104 (0%) 0/106 (0%) 1/111 (0.9%)
    Pneumonia aspiration 0/104 (0%) 1/106 (0.9%) 1/111 (0.9%)
    Pulmonary embolism 1/104 (1%) 1/106 (0.9%) 1/111 (0.9%)
    Respiratory arrest 0/104 (0%) 1/106 (0.9%) 0/111 (0%)
    Respiratory failure 0/104 (0%) 1/106 (0.9%) 1/111 (0.9%)
    Skin and subcutaneous tissue disorders
    Dry gangrene 0/104 (0%) 0/106 (0%) 1/111 (0.9%)
    Vascular disorders
    Aortic aneurysm 0/104 (0%) 1/106 (0.9%) 0/111 (0%)
    Aortic aneurysm rupture 1/104 (1%) 0/106 (0%) 0/111 (0%)
    Aortic stenosis 0/104 (0%) 1/106 (0.9%) 0/111 (0%)
    Arterial thrombosis limb 0/104 (0%) 1/106 (0.9%) 0/111 (0%)
    Deep vein thrombosis 1/104 (1%) 1/106 (0.9%) 0/111 (0%)
    Hypertension 0/104 (0%) 0/106 (0%) 1/111 (0.9%)
    Hypotension 0/104 (0%) 1/106 (0.9%) 0/111 (0%)
    Iliac artery stenosis 1/104 (1%) 0/106 (0%) 0/111 (0%)
    Orthostatic hypotension 1/104 (1%) 0/106 (0%) 0/111 (0%)
    Vascular insufficiency 1/104 (1%) 0/106 (0%) 0/111 (0%)
    Other (Not Including Serious) Adverse Events
    Verteporfin SF + Ranibizumab Verteporfin RF + Ranibizumab Ranibizumab Monotherapy
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 85/104 (81.7%) 81/106 (76.4%) 87/111 (78.4%)
    Blood and lymphatic system disorders
    Anaemia 1/104 (1%) 7/106 (6.6%) 5/111 (4.5%)
    Eye disorders
    Blepharitis (Study eye) 6/104 (5.8%) 3/106 (2.8%) 5/111 (4.5%)
    Cataract (Fellow eye) 4/104 (3.8%) 4/106 (3.8%) 6/111 (5.4%)
    Cataract (Study eye) 6/104 (5.8%) 6/106 (5.7%) 8/111 (7.2%)
    Choroidal neovascularisation (Fellow eye) 7/104 (6.7%) 12/106 (11.3%) 8/111 (7.2%)
    Conjunctival haemorrhage (Study eye) 13/104 (12.5%) 18/106 (17%) 18/111 (16.2%)
    Eye pain (Study eye) 22/104 (21.2%) 14/106 (13.2%) 14/111 (12.6%)
    Foreign body sensation in eyes (Study eye) 6/104 (5.8%) 2/106 (1.9%) 5/111 (4.5%)
    Lacrimation increased (Study eye) 6/104 (5.8%) 6/106 (5.7%) 10/111 (9%)
    Macular degeneration (Fellow eye) 8/104 (7.7%) 6/106 (5.7%) 12/111 (10.8%)
    Macular oedema (Study eye) 5/104 (4.8%) 7/106 (6.6%) 1/111 (0.9%)
    Maculopathy (Study eye) 6/104 (5.8%) 4/106 (3.8%) 2/111 (1.8%)
    Myodesopsia (Study eye) 2/104 (1.9%) 11/106 (10.4%) 10/111 (9%)
    Ocular hyperaemia (Study eye) 8/104 (7.7%) 4/106 (3.8%) 8/111 (7.2%)
    Retinal haemorrhage (Fellow eye) 6/104 (5.8%) 5/106 (4.7%) 7/111 (6.3%)
    Retinal haemorrhage (Study eye) 7/104 (6.7%) 9/106 (8.5%) 8/111 (7.2%)
    Retinal oedema (Study eye) 8/104 (7.7%) 4/106 (3.8%) 3/111 (2.7%)
    Visual acuity reduced (Fellow eye) 5/104 (4.8%) 6/106 (5.7%) 2/111 (1.8%)
    Visual acuity reduced (Study eye) 10/104 (9.6%) 9/106 (8.5%) 5/111 (4.5%)
    Vitreous detachment (Study eye) 6/104 (5.8%) 5/106 (4.7%) 4/111 (3.6%)
    Gastrointestinal disorders
    Constipation 3/104 (2.9%) 1/106 (0.9%) 6/111 (5.4%)
    Diarrhoea 5/104 (4.8%) 3/106 (2.8%) 6/111 (5.4%)
    Nausea 9/104 (8.7%) 8/106 (7.5%) 7/111 (6.3%)
    General disorders
    Fatigue 0/104 (0%) 3/106 (2.8%) 7/111 (6.3%)
    Oedema peripheral 4/104 (3.8%) 3/106 (2.8%) 6/111 (5.4%)
    Infections and infestations
    Bronchitis 8/104 (7.7%) 6/106 (5.7%) 3/111 (2.7%)
    Nasopharyngitis 10/104 (9.6%) 6/106 (5.7%) 13/111 (11.7%)
    Sinusitis 5/104 (4.8%) 8/106 (7.5%) 6/111 (5.4%)
    Upper respiratory tract infection 11/104 (10.6%) 10/106 (9.4%) 7/111 (6.3%)
    Urinary tract infection 7/104 (6.7%) 7/106 (6.6%) 9/111 (8.1%)
    Injury, poisoning and procedural complications
    Corneal abrasion (Study eye) 0/104 (0%) 1/106 (0.9%) 6/111 (5.4%)
    Fall 7/104 (6.7%) 4/106 (3.8%) 9/111 (8.1%)
    Procedural pain (Study eye) 1/104 (1%) 6/106 (5.7%) 3/111 (2.7%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 4/104 (3.8%) 7/106 (6.6%) 8/111 (7.2%)
    Back pain 6/104 (5.8%) 6/106 (5.7%) 7/111 (6.3%)
    Pain in extremity 1/104 (1%) 7/106 (6.6%) 5/111 (4.5%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma 7/104 (6.7%) 1/106 (0.9%) 1/111 (0.9%)
    Nervous system disorders
    Dizziness 6/104 (5.8%) 0/106 (0%) 7/111 (6.3%)
    Headache 7/104 (6.7%) 5/106 (4.7%) 7/111 (6.3%)
    Psychiatric disorders
    Anxiety 2/104 (1.9%) 5/106 (4.7%) 7/111 (6.3%)
    Insomnia 3/104 (2.9%) 2/106 (1.9%) 6/111 (5.4%)
    Respiratory, thoracic and mediastinal disorders
    Cough 4/104 (3.8%) 3/106 (2.8%) 6/111 (5.4%)
    Skin and subcutaneous tissue disorders
    Rash 1/104 (1%) 6/106 (5.7%) 6/111 (5.4%)
    Vascular disorders
    Hypertension 9/104 (8.7%) 13/106 (12.3%) 12/111 (10.8%)
    Hypotension 4/104 (3.8%) 2/106 (1.9%) 6/111 (5.4%)

    Limitations/Caveats

    Shorten the study duration from 24 months to 12 months based on results of the European combination study MONT BLANC (CBPD952A2309).

    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 until the publication of the trial results in their entirety.

    Results Point of Contact

    Name/Title Study Director
    Organization Novartis Pharmaceuticals
    Phone 862 778-8300
    Email
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00436553
    Other Study ID Numbers:
    • CBPD952A2308
    First Posted:
    Feb 19, 2007
    Last Update Posted:
    Apr 19, 2011
    Last Verified:
    Mar 1, 2011