Verteporfin Photodynamic Therapy Administered in Conjunction With Ranibizumab in Patients With Subfoveal Choroidal Neovascularization Secondary to Age-related Macular Degeneration (AMD)

• Sponsor: Novartis (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00433017
• Collaborator: (none)
• Enrollment: 255
• Locations: 12
• Arms: 2
• Duration (Months): 26
• Patients Per Site: 21.3
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

This study will evaluate the effect of combination therapy with verteporfin photodynamic therapy and ranibizumab on visual acuity 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
Macular Degeneration; Choroidal Neovascularization	Drug: Verteporfin Photodynamic Therapy; Drug: Ranibizumab; Drug: Placebo	Phase 2/Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 255 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 24-month Randomized, Double-masked, Controlled, Multicenter, Phase II 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 AMD.
• Study Start Date: May 1, 2007
• Actual Primary Completion Date: Jul 1, 2009
• Actual Study Completion Date: Jul 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Verteporfin + Ranibizumab Verteporfin (6 mg/m^2) photodynamic therapy (PDT) and ranibizumab (0.5 mg). Patients received three consecutive monthly ranibizumab injections starting on Day 1, and then as needed at intervals of at least 30 days based on retreatment criteria. These patients also received verteporfin PDT 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 CNV leakage assessed by fluorescein angiography (FA).	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 to the study eye, begun 15 minutes after the start of the infusion.; Other Names: Visudyne ; Drug: Ranibizumab; Ranibizumab 0.5 mg (0.05 mL of 10 mg/mL solution for injection) administered as an intravitreal injection; Other Names: Lucentis
Active Comparator: Ranibizumab Monotherapy Patients received three consecutive monthly ranibizumab injections starting on Day 1 and then as needed from Month 3 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. 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 CNV leakage assessed by fluorescein angiography (FA).	Drug: Ranibizumab; Ranibizumab 0.5 mg (0.05 mL of 10 mg/mL solution for injection) administered as an intravitreal injection; Other Names: Lucentis ; Drug: Placebo; As a placebo for verteporfin photodynamic therapy (for masking purposes), 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.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Best-corrected Visual Acuity (BCVA) 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 Participants With a Treatment-free Interval of at Least 3 Months Following the Month 2 Visit [Month 2 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. Percentage of Patients With Fluorescein Leakage in the Study Eye at Month 12 [Month 12]

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

2. Mean Change in Total Area of Leakage (Observed) of the Study Eye at Month 12 [Baseline and Month 12]

   Fluorescein angiography (FA) was used to assess the mean change of leakage of the study eye at the Central Reading Center (CRC). A negative change from baseline indicates improvement, ie, less leakage.

3. Mean Change in Central Retinal Thickness of the Study Eye at Month 12 [Baseline and Month 12]

   Optical coherence tomography (OCT) was used to assess the mean change in retinal thickness of the study eye at the Central Reading Center (CRC). A negative change from baseline indicates improvement, ie, less thickness.

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 choriodal neovascularization (CNV) due to age-related macular degeneration (AMD)

Exclusion Criteria:

• Choriodal 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	Wien		Austria
2	Novartis Investigative site	Antwerpen		Belgium
3	Novartis Investigative site	Aalborg		Denmark
4	Novartis Investigative site	Creteil		France
5	Novartis Investigative site	Regensburg		Germany
6	Novartis Investigative site	Budapest		Hungary
7	Novartis Investigative site	Firenze		Italy
8	Novartis Investigative site	Rotterdam		Netherlands
9	Novartis Investigative site	Warszawa		Poland
10	Novartis Investigative site	Madrid		Spain
11	Novartis Investigative site	Geneve		Switzerland
12	Novartis Investigative site	Manchester		United Kingdom

Sponsors and Collaborators

• Novartis

Investigators

• Study Chair: Novartis, Novartis

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00433017
• Other Study ID Numbers: CBPD952A2309
• First Posted: Feb 9, 2007
• Last Update Posted: Apr 21, 2011
• Last Verified: Apr 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

Arm/Group Title	Verteporfin + Ranibizumab	Ranibizumab
Arm/Group Description	Patients received three consecutive monthly ranibizumab injections starting on Day 1, and then as needed at intervals of at least 30 days based on retreatment criteria. These patients also received verteporfin PDT 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 CNV leakage assessed by fluorescein angiography (FA).	Patients received three consecutive monthly ranibizumab injections starting on Day 1 and then as needed from Month 3 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. 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 CNV leakage assessed by fluorescein angiography (FA).
Period Title: Overall Study
STARTED	122	133
Completed 12 Month Phase	114	126
COMPLETED	26	32
NOT COMPLETED	96	101

Baseline Characteristics

Arm/Group Title	Verteporfin + Ranibizumab	Ranibizumab	Total
Arm/Group Description	Patients received three consecutive monthly ranibizumab injections starting on Day 1, and then as needed at intervals of at least 30 days based on retreatment criteria. These patients also received verteporfin PDT 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 CNV leakage assessed by fluorescein angiography (FA).	Patients received three consecutive monthly ranibizumab injections starting on Day 1 and then as needed from Month 3 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. 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 CNV leakage assessed by fluorescein angiography (FA).	Total of all reporting groups
Overall Participants	122	133	255
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	76.8 (7.65)	75.5 (7.44)	76.1 (7.55)
Sex: Female, Male (Count of Participants)
Female	78 63.9%	74 55.6%	152 59.6%
Male	44 36.1%	59 44.4%	103 40.4%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Best-corrected Visual Acuity (BCVA) 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

Performed on the Full analysis set (FAS) using the Last Observation Carried Forward (LOCF) approach for imputing missing data. FAS consisted of all patients as randomized that received at least one application of study drug and had at least one post-baseline assessment for best corrected visual acuity in the study eye.

Arm/Group Title	Verteporfin + Ranibizumab	Ranibizumab
Arm/Group Description	Patients received three consecutive monthly ranibizumab injections starting on Day 1, and then as needed at intervals of at least 30 days based on retreatment criteria. These patients also received verteporfin PDT 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 CNV leakage assessed by fluorescein angiography (FA).	Patients received three consecutive monthly ranibizumab injections starting on Day 1 and then as needed from Month 3 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. 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 CNV leakage assessed by fluorescein angiography (FA).
Measure Participants	121	132
Baseline	54.6 (13.5)	55.1 (12.3)
Month 12	57.1 (18.3)	59.4 (18.8)
Change from Baseline	2.5 (14.82)	4.4 (15.92)

2. Primary Outcome

Title	Percent of Participants 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 to Month 11

Outcome Measure Data

Analysis Population Description

Full analysis set. Includes number of participants in the treatment group with at least one visit assessment of re-treatment.

Arm/Group Title	Verteporfin + Ranibizumab	Ranibizumab
Arm/Group Description	Patients received three consecutive monthly ranibizumab injections starting on Day 1, and then as needed at intervals of at least 30 days based on retreatment criteria. These patients also received verteporfin PDT 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 CNV leakage assessed by fluorescein angiography (FA).	Patients received three consecutive monthly ranibizumab injections starting on Day 1 and then as needed from Month 3 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. 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 CNV leakage assessed by fluorescein angiography (FA).
Measure Participants	119	128
Number [Percentage of Participants]	95.8 78.5%	92.2 69.3%

3. Secondary Outcome

Title	Percentage of Patients With Fluorescein Leakage in the Study Eye at Month 12
Description	The proportion 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

The Full Analysis Set (FAS) based on observed data.

Arm/Group Title	Verteporfin + Ranibizumab	Ranibizumab
Arm/Group Description	Patients received three consecutive monthly ranibizumab injections starting on Day 1, and then as needed at intervals of at least 30 days based on retreatment criteria. These patients also received verteporfin PDT 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 CNV leakage assessed by fluorescein angiography (FA).	Patients received three consecutive monthly ranibizumab injections starting on Day 1 and then as needed from Month 3 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. 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 CNV leakage assessed by fluorescein angiography (FA).
Measure Participants	97	115
Number [Percentage of participants]	28.9 23.7%	25.2 18.9%

4. Secondary Outcome

Title	Mean Change in Total Area of Leakage (Observed) of the Study Eye at Month 12
Description	Fluorescein angiography (FA) was used to assess the mean change of leakage of the study eye at the Central Reading Center (CRC). A negative change from baseline indicates improvement, ie, less leakage.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

Full analysis set based on observed data.

Arm/Group Title	Verteporfin + Ranibizumab	Ranibizumab
Arm/Group Description	Patients received three consecutive monthly ranibizumab injections starting on Day 1, and then as needed at intervals of at least 30 days based on retreatment criteria. These patients also received verteporfin PDT 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 CNV leakage assessed by fluorescein angiography (FA).	Patients received three consecutive monthly ranibizumab injections starting on Day 1 and then as needed from Month 3 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. 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 CNV leakage assessed by fluorescein angiography (FA).
Measure Participants	92	107
Baseline	7.4 (4.63)	8.1 (5.82)
Month 12	2.2 (4.88)	2.0 (4.68)
Change from Baseline	-5.3 (5.32)	-6.1 (6.44)

5. Secondary Outcome

Title	Mean Change in Central Retinal Thickness of the Study Eye at Month 12
Description	Optical coherence tomography (OCT) was used to assess the mean change in retinal thickness of the study eye at the Central Reading Center (CRC). A negative change from baseline indicates improvement, ie, less thickness.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

Full analysis set, LOCF

Arm/Group Title	Verteporfin + Ranibizumab	Ranibizumab
Arm/Group Description	Patients received three consecutive monthly ranibizumab injections starting on Day 1, and then as needed at intervals of at least 30 days based on retreatment criteria. These patients also received verteporfin PDT 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 CNV leakage assessed by fluorescein angiography (FA).	Patients received three consecutive monthly ranibizumab injections starting on Day 1 and then as needed from Month 3 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. 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 CNV leakage assessed by fluorescein angiography (FA).
Measure Participants	119	128
Baseline	335.2 (94.7)	339.8 (125.6)
Month 12	219.9 (61.1)	232.0 (54.5)
Change from Baseline	-115.3 (98.7)	-107.7 (124.6)

Adverse Events

Time Frame	Includes cumulative data through 24 months.
Arm/Group Title	Verteporfin + Ranibizumab		Ranibizumab
Arm/Group Description	Patients received three consecutive monthly ranibizumab injections starting on Day 1, and then as needed at intervals of at least 30 days based on retreatment criteria. These patients also received verteporfin PDT 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 CNV leakage assessed by fluorescein angiography (FA).		Patients received three consecutive monthly ranibizumab injections starting on Day 1 and then as needed from Month 3 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. 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 CNV leakage assessed by fluorescein angiography (FA).
All Cause Mortality
	Verteporfin + Ranibizumab		Ranibizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Verteporfin + Ranibizumab		Ranibizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/122 (20.5%)		28/133 (21.1%)
Cardiac disorders
ANGINA PECTORIS	1/122 (0.8%)		1/133 (0.8%)
ARRHYTHMIA	0/122 (0%)		1/133 (0.8%)
ATRIAL FIBRILLATION	1/122 (0.8%)		0/133 (0%)
ATRIAL FLUTTER	0/122 (0%)		1/133 (0.8%)
CARDIAC FAILURE	2/122 (1.6%)		0/133 (0%)
CARDIAC VALVE DISEASE	1/122 (0.8%)		0/133 (0%)
CORONARY ARTERY DISEASE	1/122 (0.8%)		0/133 (0%)
MYOCARDIAL INFARCTION	2/122 (1.6%)		0/133 (0%)
MYOCARDIAL ISCHAEMIA	1/122 (0.8%)		0/133 (0%)
Eye disorders
CATARACT (Fellow eye)	0/122 (0%)		1/133 (0.8%)
CATARACT (Study eye)	0/122 (0%)		2/133 (1.5%)
CHORIORETINAL ATROPHY (Study eye)	1/122 (0.8%)		0/133 (0%)
GLAUCOMA (Fellow eye)	0/122 (0%)		1/133 (0.8%)
GLAUCOMA (Study eye)	0/122 (0%)		1/133 (0.8%)
LAGOPHTHALMOS (Fellow eye)	1/122 (0.8%)		0/133 (0%)
PARALYTIC LAGOPHTHALMOS (Study eye)	0/122 (0%)		1/133 (0.8%)
RETINAL ARTERY OCCLUSION (Study eye)	0/122 (0%)		1/133 (0.8%)
RETINAL CYST (Study eye)	1/122 (0.8%)		0/133 (0%)
RETINAL DEGENERATION (Study eye)	1/122 (0.8%)		0/133 (0%)
RETINAL OEDEMA (Study eye)	1/122 (0.8%)		0/133 (0%)
ULCERATIVE KERATITIS (Fellow eye)	1/122 (0.8%)		0/133 (0%)
VISUAL ACUITY REDUCED (Study eye)	2/122 (1.6%)		1/133 (0.8%)
Gastrointestinal disorders
DIARRHOEA	0/122 (0%)		1/133 (0.8%)
GASTRITIS	0/122 (0%)		1/133 (0.8%)
GASTROINTESTINAL HAEMORRHAGE	1/122 (0.8%)		0/133 (0%)
HAEMORRHOIDS	1/122 (0.8%)		0/133 (0%)
HIATUS HERNIA	0/122 (0%)		1/133 (0.8%)
NAUSEA	0/122 (0%)		1/133 (0.8%)
SALIVARY GLAND CALCULUS	0/122 (0%)		1/133 (0.8%)
VISCEROPTOSIS	1/122 (0.8%)		0/133 (0%)
General disorders
OEDEMA PERIPHERAL	1/122 (0.8%)		1/133 (0.8%)
Hepatobiliary disorders
BILE DUCT STENOSIS	0/122 (0%)		1/133 (0.8%)
BILE DUCT STONE	0/122 (0%)		1/133 (0.8%)
Infections and infestations
ERYSIPELAS	1/122 (0.8%)		0/133 (0%)
LABYRINTHITIS	0/122 (0%)		1/133 (0.8%)
MASTOIDITIS	0/122 (0%)		1/133 (0.8%)
PNEUMONIA	1/122 (0.8%)		0/133 (0%)
SIALOADENITIS	0/122 (0%)		1/133 (0.8%)
WOUND INFECTION	1/122 (0.8%)		0/133 (0%)
Injury, poisoning and procedural complications
CARTILAGE INJURY	1/122 (0.8%)		0/133 (0%)
CONTUSION	1/122 (0.8%)		0/133 (0%)
FALL	4/122 (3.3%)		2/133 (1.5%)
FEMUR FRACTURE	1/122 (0.8%)		0/133 (0%)
HEAD INJURY	0/122 (0%)		1/133 (0.8%)
HIP FRACTURE	1/122 (0.8%)		0/133 (0%)
JOINT DISLOCATION	1/122 (0.8%)		0/133 (0%)
LUMBAR VERTEBRAL FRACTURE	1/122 (0.8%)		0/133 (0%)
MULTIPLE INJURIES	0/122 (0%)		1/133 (0.8%)
UPPER LIMB FRACTURE	1/122 (0.8%)		0/133 (0%)
Investigations
CARBOHYDRATE ANTIGEN 125 INCREASED	1/122 (0.8%)		0/133 (0%)
Metabolism and nutrition disorders
HYPOKALAEMIA	0/122 (0%)		1/133 (0.8%)
Musculoskeletal and connective tissue disorders
BACK PAIN	1/122 (0.8%)		0/133 (0%)
MUSCULAR WEAKNESS	1/122 (0.8%)		0/133 (0%)
MUSCULOSKELETAL CHEST PAIN	1/122 (0.8%)		0/133 (0%)
MUSCULOSKELETAL PAIN	1/122 (0.8%)		0/133 (0%)
OSTEOPOROSIS	0/122 (0%)		1/133 (0.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BLADDER NEOPLASM	0/122 (0%)		1/133 (0.8%)
BREAST CANCER	1/122 (0.8%)		0/133 (0%)
GENITAL NEOPLASM MALIGNANT FEMALE	1/122 (0.8%)		0/133 (0%)
MEDIASTINUM NEOPLASM	1/122 (0.8%)		0/133 (0%)
METASTASES TO PERITONEUM	1/122 (0.8%)		0/133 (0%)
PROSTATE CANCER	1/122 (0.8%)		0/133 (0%)
RENAL NEOPLASM	0/122 (0%)		2/133 (1.5%)
SKIN CANCER	1/122 (0.8%)		0/133 (0%)
Nervous system disorders
CAROTID ARTERY STENOSIS	0/122 (0%)		1/133 (0.8%)
CEREBRAL ISCHAEMIA	1/122 (0.8%)		0/133 (0%)
CEREBROVASCULAR ACCIDENT	1/122 (0.8%)		4/133 (3%)
DIZZINESS	0/122 (0%)		2/133 (1.5%)
FACIAL PARESIS	0/122 (0%)		1/133 (0.8%)
TRANSIENT ISCHAEMIC ATTACK	0/122 (0%)		1/133 (0.8%)
Respiratory, thoracic and mediastinal disorders
PLEURAL EFFUSION	1/122 (0.8%)		0/133 (0%)
Skin and subcutaneous tissue disorders
SKIN ULCER	0/122 (0%)		1/133 (0.8%)
Vascular disorders
AORTIC ANEURYSM	1/122 (0.8%)		1/133 (0.8%)
ARTERIAL STENOSIS LIMB	1/122 (0.8%)		0/133 (0%)
ARTERIAL THROMBOSIS LIMB	1/122 (0.8%)		0/133 (0%)
DEEP VEIN THROMBOSIS	0/122 (0%)		1/133 (0.8%)
ILIAC ARTERY OCCLUSION	1/122 (0.8%)		0/133 (0%)
ORTHOSTATIC HYPOTENSION	0/122 (0%)		1/133 (0.8%)
PERIPHERAL ARTERIAL OCCLUSIVE DISEASE	2/122 (1.6%)		0/133 (0%)
THROMBOSIS	1/122 (0.8%)		1/133 (0.8%)
Other (Not Including Serious) Adverse Events
	Verteporfin + Ranibizumab		Ranibizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	64/122 (52.5%)		63/133 (47.4%)
Eye disorders
CONJUNCTIVAL HAEMORRHAGE (Study eye)	4/122 (3.3%)		10/133 (7.5%)
EYE PAIN (Study eye)	10/122 (8.2%)		8/133 (6%)
MACULAR DEGENERATION (Fellow eye)	4/122 (3.3%)		8/133 (6%)
OCULAR HYPERAEMIA (Study eye)	7/122 (5.7%)		10/133 (7.5%)
RETINAL HAEMORRHAGE (Study eye)	7/122 (5.7%)		5/133 (3.8%)
Infections and infestations
BRONCHITIS	5/122 (4.1%)		7/133 (5.3%)
INFLUENZA	3/122 (2.5%)		9/133 (6.8%)
NASOPHARYNGITIS	18/122 (14.8%)		15/133 (11.3%)
Investigations
INTRAOCULAR PRESSURE INCREASED (Study eye)	11/122 (9%)		8/133 (6%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	8/122 (6.6%)		3/133 (2.3%)
Vascular disorders
HYPERTENSION	19/122 (15.6%)		13/133 (9.8%)

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