Dose Ranging Study of Pazopanib to Treat Neovascular Age-Related Macular Degeneration

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01134055
• Collaborator: (none)
• Enrollment: 510
• Locations: 77
• Arms: 7
• Actual Duration (Months): 28
• Patients Per Site: 6.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the safety and efficacy of different dosage regimens of pazopanib eye drops for the treatment of neovascular age-related macular degeneration.

Condition or Disease	Intervention/Treatment	Phase
Macular Degeneration	Drug: pazopanib eye drops; Drug: placebo; Biological: ranibizumab intravitreal injection	Phase 2

Detailed Description

MD7110852 is a Phase 2b dose-ranging study designed to demonstrate the 1 year efficacy and safety of pazopanib eye drops for the treatment of neovascular age related macular degeneration (AMD) in subjects whose disease is currently managed with anti-VEGF (vascular endothelial growth factor) injection therapy. Eye drop regimens are double-masked with placebo eye drops and will have access to open-label ranibizumab intravitreal (IVT) injection if needed. The ranibizumab IVT injection every 4 weeks control arm is open-label.

Study Design

• Study Type: Interventional
• Actual Enrollment: 510 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: MD7110852, A Phase 2b Dose-Ranging Study of Pazopanib Eye Drops Versus Ranibizumab Intravitreal Injections for the Treatment of Neovascular Age-Related Macular Degeneration
• Actual Study Start Date: Jun 1, 2010
• Actual Primary Completion Date: Oct 1, 2012
• Actual Study Completion Date: Oct 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: investigational arm 1 5 mg/mL pazopanib eye drops TID with allowance for as-needed ranibizumab injection	Drug: pazopanib eye drops; A tyrosine kinase inhibitor of multiple receptors including vascular endothelial growth factor receptors and platelet-derived growth factor receptors.
Experimental: investigational arm 2 5 mg/mL pazopanib eye drops QID with allowance for as-needed ranibizumab injection	Drug: pazopanib eye drops; A tyrosine kinase inhibitor of multiple receptors including vascular endothelial growth factor receptors and platelet-derived growth factor receptors.
Experimental: investigational arm 3 10 mg/mL pazopanib eye drops BID with allowance for as-needed ranibizumab injection	Drug: pazopanib eye drops; A tyrosine kinase inhibitor of multiple receptors including vascular endothelial growth factor receptors and platelet-derived growth factor receptors.
Experimental: investigational arm 4 10 mg/mL pazopanib eye drops TID with allowance for as-needed ranibizumab injection	Drug: pazopanib eye drops; A tyrosine kinase inhibitor of multiple receptors including vascular endothelial growth factor receptors and platelet-derived growth factor receptors.
Experimental: investigational arm 5 10 mg/mL pazopanib eye drops QID with allowance for as-needed ranibizumab injection	Drug: pazopanib eye drops; A tyrosine kinase inhibitor of multiple receptors including vascular endothelial growth factor receptors and platelet-derived growth factor receptors.
Placebo Comparator: placebo control arm Placebo eye drops QID with allowance for as-needed ranibizumab injection	Drug: placebo; placebo eye drops
Active Comparator: active open-label control arm Ranibizumab intravitreal injection every 4 weeks	Biological: ranibizumab intravitreal injection; Humanized recombinant monoclonal antibody fragment targeted against human vascular endothelial growth factor A

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Best-corrected Visual Acuity (BCVA) as Measured by the Number of Letters Read on the Early Treatment of Diabetic Retinopathy Study (ETDRS) Grading Charts at a Starting Distance of 4 Meters at Week 52 [Day 1 and 52 weeks]

   BCVA was measured in the study eye using the ETDRS grading charts starting at a test distance of 4 meters. The ETDRS grading chart was of at least 24 to 78 letters. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. There were seven cut off points in change from baseline visual acuity on ETDRS grading chart which are, 15 to 29, 10 to 14, 5 to 9, -4 to 4, -5 to -9, -10 to -14 and -15 to -29 letters. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. If either the baseline or post-randomization value was missing, the change from baseline was set to missing as well. Day 1 values are considered as Baseline in this study.

Secondary Outcome Measures

1. Percentage of Ranibizumab Re-injections Received Over 28 and 52 Weeks [Up to 52 weeks]

   The investigator interpreted each Week 4 to Week 52 Optical coherence tomography (OCT) scan, BCVA score, and available Fluorescein angiography (FA)/Fundus photography (FP) and re-injected if one or more criteria were met. The criteria were: Evidence of Intraretinal (IR) (with or without cysts) fluid or Subretinal (SR) fluid, a serous retinal pigment epithelial detachment, a notable decline in Visual Acuity, new SR or IR macular hemorrhage that the investigator judges is associated with Choroidal neovascularization, increased lesion size on FA relative to the last angiogram as judged by the investigator or leakage on FA that the investigator judges would benefit from re-injection. Injection rate over 52 weeks was computed by taking the number of injections received divided by the number of visits for the participant. Likewise for 28 weeks it was estimated as the number of post baseline injections received divided by the number of post baseline visits at or before the week 28 visit.

2. Number of Participants With BCVA Over Time [Up to Week 52]

   BCVA was measured in the study eye using the ETDRS grading charts starting at a test distance of 4 meters. The ETDRS grading chart was of at least 24 to 78 letters. There were seven cut off points in change from baseline visual acuity on ETDRS grading chart which are, 15 to 29, 10 to 14, 5 to 9, -4 to 4, -5 to -9, -10 to -14 and -15 to -29 letters.

3. Number of Participants Analyzed for Visual Acuity (VA) Response Over Time [Week 52]

   VA was measured in the study eye using the ETDRS grading charts starting at a test distance of 4 meters.The ETDRS grading chart was of at least 24 to 78 letters. There were seven cut off points in change from baseline visual acuity on ETDRS grading chart which are, 15 to 29, 10 to 14, 5 to 9, -4 to 4, -5 to -9, -10 to -14 and -15 to -29 letters. This outcome measure contains the number of participants who were analyzed for VA response.

4. Change From Baseline in Center Point Thickness (CPT) Over Time [Baseline and Week 52]

   CPT was the inner limiting membrane to the beginning of the retinal pigment epithelium (RPE) inclusive of SR fluid. The outer boundary included the outer segment of the photoreceptors and not included the RPE. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. If either the baseline or post-randomization value was missing, the change from baseline was set to missing as well. Day 1 values are considered as Baseline in this study. In amendment 3, inclusion criterion number 5 was revised to remove the required quantitative OCT component. OCT examination was used to supplement FA findings and provided qualitative (presence of SR and/or IR fluid) and quantitative (a CPT that is at least 250 microns) evidence of an active subfoveal lesion. Hence data for pre and post amendment have been provided separately.

5. Number of Participants That Met Criteria for Re-injection [Up to Week 52]

   The investigator interpreted each Week 4 to Week 52 Optical coherence tomography (OCT) scan, BCVA score, and available Fluorescein angiography (FA)/Fundus photography (FP) and re-injected if one or more criteria were met. The criteria were: Evidence of Intraretinal (IR) (with or without cysts) fluid or Subretinal (SR) fluid, a serous retinal pigment epithelial detachment, a notable decline in Visual Acuity, new SR or IR macular hemorrhage that the investigator judges is associated with Choroidal neovascularization, increased lesion size on FA relative to the last angiogram as judged by the investigator or leakage on FA that the investigator judges would benefit from re-injection.

6. Change From Baseline in the Area of Choroidal Neovascularisation (CNV) [Day 1, Week 28 and Week 52]

   Choroidal neovascularisation is progressive worsening of vision that can cause hemorrhage and exudation, and finally disciform scarring and retinal atrophy. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. If either the baseline or post-randomization value was missing, the change from baseline was set to missing as well. Day 1 values are considered as Baseline in this study.

7. Change From Baseline in the Area of the CNV Lesion Complex (i.e. CNV, Blood, PED, and Fibrosis) [Day 1, Week 28 and Week 52]

   CNV is progressive worsening of vision that can cause hemorrhage and exudation, and finally disciform scarring and retinal atrophy. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. If either the baseline or post-randomization value was missing, the change from baseline was set to missing as well. Day 1 values are considered as Baseline in this study.

8. Change From Baseline in the Area of Fluorescein Leakage [Day 1, Week 28 and Week 52]

   Fluorescein angiograms was performed at the Screening, Week 12, Week 28, and Week 52 Visits. All images, including any that were performed at the investigator's medical discretion, were transferred to the FPRC. Fluorescein was injected intravenously according to usual clinic procedures. Dose response was also examined under different aspects of re-injection, such as time to first injection, the percentage of participants that required an injection by Week 28, as well as the estimation of the probability of reinjection. FA assessments of area of fluorescein leakage, CNV area and area of CNV lesion complex were also examined for dose differentiation.

9. Change in Area of Serous Sensory Retinal Detachment (SSRD) [Day 1, Week 28 and Week 52]

   This is an Optical coherence tomography (OCT) parameter used to manually measure thickness along any scan. OCT was performed at week 28 and week 52.

10. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Up to 52 Weeks]

    An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect.

11. Summary of Potentially Clinically Important Findings for Ophthalmic Examinations [Up to Week 52]

    Opthalmicexaminations were done on Ocular alignment and motility, pupillary function, and visual fields by confrontation. Slit-lamp biomicroscopic examination of the anterior segment structure was performed. Fundus slit-lamp biomicroscopic examination, including use of accessory diagnostic lenses, to view the vitreous, retina (including posterior pole and periphery), macula, vasculature, and optic nerve was also performed. These examinations were performed on the study eye (SE) and the Fellow eye (FE). Participants with abnormal findings are listed here.

12. Summary of Intraocular Pressure Exam Findings [Up to week 52]

    Intraocular pressure (IOP) measurement was done with Goldmann tonometer. Intraocular pressure was measured prior to dilating the pupil and, to account for diurnal variation, at approximately the same time of day for every visit.

13. Number of Participants With Vital Sign Values Outside of Clinical Concern Range [Up to Week 52]

    Vital signs including systolic and diastolic blood pressure and heart rate were measured throughout the study. Number of participants with vital signs outside of clinical concern Range were summarized. 'High' denotes above normal range and 'Low' denotes below normal range for all the categories. The potential clinical importance ranges (low and high) of the vital sign parameters were for systolic blood pressure (<85 and >160 millimeter of mercury [mmHg]), diastolic blood pressure (<45 and >100 mmHg) and heart rate (<40 and >110 beats per minute). Only those parameters for which at least one value of potential clinical importance was reported are summarized. The number of participants with potential clinical important vital parameter findings at any visit were reported.

14. Summary of Abnormal Electrocardiogram (ECG) Findings [Week 4, Week 28, Week 44 and Week 52]

    12-Lead ECGs were performed in triplicate and were obtained on Weeks 4 to Week 28 and Week 52. The on-treatment ECGs were used to ascertain any risk of QTc interval prolongation at extremely low pazopanib exposures compared to what was routinely observed in participants with cancer. The on-treatment ECG data collected from participants assigned to one of the control arms also provided ECG background rate data for participants not exposed to pazopanib. Participants with Clinically significant abnormal ECGs are included here.

15. Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern [Up to Week 52]

    The Laboratory Parameters included Alanine Amino Transferase (ALT), Albumin, Alkaline Phosphatase, Aspartate Amino Transferase (AST), Calcium, Bicarbonate, Creatinine, Glucose, Hemoglobin, Lymphocytes, Platelet count, Potassium, Sodium, Thyroid Stimulating Hormone (TSH), Total Bilirubin, Total Neutrophils, Blood Urea Nitrogen (BUN) and White Blood Cell count (WBC). Number of participants with Laboratory outside of clinical concern Range were summarized here. Data of high and low from the clinical concern range has been provided here. Here 'High' denotes above normal range and 'Low' denotes below normal range for all the categories.

16. Number of Participants With Laboratory Data of Clinical Concern for Urine Protein [Day 1 to Week 28 and Week 52]

    Urine Samples were collected from Day 1 to Week 28 and Week 52 for analyses. In this dipstick test, the level of protein in urine samples was recorded as negative (Neg), trace (tr), 1+, 2+, and 3+ (the plus sign increases with a higher level of proteins in the urine: 1+=slightly positive, 2+=positive, 3+=high positive). Neg indicated no proteinuria and 3+(high positive) indicated worst proteinuria.

17. Plasma Concentrations of Pazopanib [Week 4, Week 24 and Week 52]

    All participants in the eye drop containing arms had a single blood sample drawn for assessment of pazopanib plasma concentration at the Week 4, Week 24 and Week 24. The sample was drawn without restriction for the time interval between blood draw and the last dose of IP eye drops.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Men and women aged ≥50 years.

• Active subfoveal choroidal neovascularization (CNV) lesion secondary to AMD in study eye: Total lesion area ≤12 disc areas with CNV ≥50% total lesion area.

• Anti-Vascular endothelial growth factor (VEGF) intravitreal injection experienced and in need of re-treatment.

• Best-corrected visual acuity of at least 24 letters (equates to approximately 20/320 Snellen equivalents or better).

Exclusion Criteria:

• Prior ocular investigational drug/device for choroidal neovascularization, photodynamic therapy, radiation, subfoveal or juxtafoveal focal laser photocoagulation.

• Prior failure to anti-VEGF intravitreal injection therapy.

• Recent ocular investigational drug/device for non-CNV condition.

• Prior ocular surgeries (vitrectomy, scleral buckle, or glaucoma filtering/shunt surgery). Cataract surgery permitted if ≥3 months and has posterior chamber intraocular lens.

• Center-fovea involvement of any of the following: fibrosis, atrophy, serous retinal pigment epithelial detachment, or retinal pigment epithelial tear.

• CNV in either eye due to other causes.

• Clinical evidence of diabetic retinopathy or diabetic macular edema.

• Recent myocardial infarction or cerebrovascular accident.

• Uncontrolled hypertension in spite of antihypertensive medications.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Peoria	Arizona	United States	85381
2	GSK Investigational Site	Phoenix	Arizona	United States	85014
3	GSK Investigational Site	Phoenix	Arizona	United States	85020
4	GSK Investigational Site	Tucson	Arizona	United States	85704
5	GSK Investigational Site	Tucson	Arizona	United States	85710
6	GSK Investigational Site	Irvine	California	United States	92697
7	GSK Investigational Site	Loma Linda	California	United States	92354
8	GSK Investigational Site	Poway	California	United States	92064
9	GSK Investigational Site	Santa Ana	California	United States	92705
10	GSK Investigational Site	Golden	Colorado	United States	80401
11	GSK Investigational Site	Fort Myers	Florida	United States	33901
12	GSK Investigational Site	Winter Haven	Florida	United States	33880
13	GSK Investigational Site	Chicago	Illinois	United States	60612
14	GSK Investigational Site	Leawood	Kansas	United States	66211
15	GSK Investigational Site	Paducah	Kentucky	United States	42001
16	GSK Investigational Site	Baltimore	Maryland	United States	21287
17	GSK Investigational Site	Boston	Massachusetts	United States	02114
18	GSK Investigational Site	Royal Oak	Michigan	United States	48073
19	GSK Investigational Site	Traverse City	Michigan	United States	49686
20	GSK Investigational Site	New York	New York	United States	10003
21	GSK Investigational Site	Asheville	North Carolina	United States	28803
22	GSK Investigational Site	Chapel Hill	North Carolina	United States	27599
23	GSK Investigational Site	Charlotte	North Carolina	United States	28210
24	GSK Investigational Site	Beachwood	Ohio	United States	44122
25	GSK Investigational Site	Cleveland	Ohio	United States	44130
26	GSK Investigational Site	Cleveland	Ohio	United States	44195
27	GSK Investigational Site	Columbus	Ohio	United States	43212
28	GSK Investigational Site	Ashland	Oregon	United States	97520
29	GSK Investigational Site	Portland	Oregon	United States	97239
30	GSK Investigational Site	Philadelphia	Pennsylvania	United States	19107
31	GSK Investigational Site	Austin	Texas	United States	78705
32	GSK Investigational Site	Dallas	Texas	United States	75231
33	GSK Investigational Site	Fort Worth	Texas	United States	76104
34	GSK Investigational Site	Salt Lake City	Utah	United States	84107
35	GSK Investigational Site	Seattle	Washington	United States	98104
36	GSK Investigational Site	Silverdale	Washington	United States	98383
37	GSK Investigational Site	Madison	Wisconsin	United States	53705
38	GSK Investigational Site	Sydney	New South Wales	Australia	2000
39	GSK Investigational Site	Sydney	New South Wales	Australia	2150
40	GSK Investigational Site	Melbourne	Victoria	Australia
41	GSK Investigational Site	Nedlands	Western Australia	Australia	6009
42	GSK Investigational Site	Bruxelles		Belgium	1020
43	GSK Investigational Site	Liège		Belgium	4000
44	GSK Investigational Site	Vancouver	British Columbia	Canada	V5Z 3N9
45	GSK Investigational Site	Victoria	British Columbia	Canada	V8V 4X3
46	GSK Investigational Site	Halifax	Nova Scotia	Canada	B3H 2Y9
47	GSK Investigational Site	London	Ontario	Canada	N6A 4V2
48	GSK Investigational Site	Mississauga	Ontario	Canada	L4W 1W9
49	GSK Investigational Site	Toronto	Ontario	Canada	M4N 3M5
50	GSK Investigational Site	Aarhus		Denmark	DK-8000
51	GSK Investigational Site	Glostrup		Denmark
52	GSK Investigational Site	Freiburg	Baden-Wuerttemberg	Germany	79106
53	GSK Investigational Site	Tuebingen	Baden-Wuerttemberg	Germany	72076
54	GSK Investigational Site	Muenchen	Bayern	Germany	80336
55	GSK Investigational Site	Bonn	Nordrhein-Westfalen	Germany	53127
56	GSK Investigational Site	Dresden	Sachsen	Germany	01307
57	GSK Investigational Site	Leipzig	Sachsen	Germany	04103
58	GSK Investigational Site	Kiel	Schleswig-Holstein	Germany	24105
59	GSK Investigational Site	Udine	Friuli-Venezia-Giulia	Italy	33100
60	GSK Investigational Site	Milano	Lombardia	Italy	20132
61	GSK Investigational Site	Milano	Lombardia	Italy	20157
62	GSK Investigational Site	Torino	Piemonte	Italy	10122
63	GSK Investigational Site	Padova	Veneto	Italy	35128
64	GSK Investigational Site	Aichi		Japan	460-0011
65	GSK Investigational Site	Aichi		Japan	462-0825
66	GSK Investigational Site	Aichi		Japan	466-8560
67	GSK Investigational Site	Chiba		Japan	279-0021
68	GSK Investigational Site	Fukuoka		Japan	812-8582
69	GSK Investigational Site	Fukushima		Japan	960-1295
70	GSK Investigational Site	Hokkaido		Japan	001-0016
71	GSK Investigational Site	Hokkaido		Japan	060-8604
72	GSK Investigational Site	Kagawa		Japan	761-0793
73	GSK Investigational Site	Tokyo		Japan	101-8309
74	GSK Investigational Site	Linköping		Sweden	SE-581 85
75	GSK Investigational Site	Stockholm		Sweden	SE-112 82
76	GSK Investigational Site	Uppsala		Sweden	SE-751 85
77	GSK Investigational Site	Örebro		Sweden	SE-701 85

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01134055
• Other Study ID Numbers: 110852
• First Posted: May 31, 2010
• Last Update Posted: Jan 8, 2018
• Last Verified: Dec 1, 2017

• Keywords provided by GlaxoSmithKline: ranibizumab; wet AMD; MD7110852; age related macular degeneration; age-related macular degeneration; macular degeneration; pazopanib
• Additional relevant MeSH terms: Macular Degeneration; Ranibizumab; Ophthalmic Solutions

Study Results

Participant Flow

Recruitment Details	This was a multicenter, randomized, parallel-group, double-masked eye drops, and active-controlled study from 01 June 2010 to 05 October 2012. The study was conducted at 77 sites in 9 countries from North America, Europe, Australia and Japan.
Pre-assignment Detail	A total of 510 participants were randomized for the study. After a 1-2 week screening period, participants entered a 52-week treatment period. There were 449 screen failures in this study.

Arm/Group Title	Placebo Control Arm QID	Pazopanib Eye Drops 5 mg/mL TID	Pazopanib Eye Drops 5 mg/mL QID	Pazopanib Eye Drops 10 mg/mL BID	Pazopanib Eye Drops 10 mg/mL TID	Pazopanib Eye Drops 10 mg/mL QID	Ranibizumab Injections Active Open-label Control Arm
Arm/Group Description	Only the study eye (one eye) per participant enrolled in the study received Placebo QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week treatment period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 milligram/milliliter (mg/mL) TID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL twice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL thrice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL four times daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Participants enrolled in this arm received no eye drops. They received a 0.20 mL to 0.23 mL fill of 10 mg/mL Ranibizumab injection once every four weeks throughout the entire 52 weeks of the study.
Period Title: Overall Study
STARTED	73	72	74	73	73	72	73
COMPLETED	65	66	71	67	67	65	62
NOT COMPLETED	8	6	3	6	6	7	11

Baseline Characteristics

Arm/Group Title	Placebo Control Arm QID	Pazopanib Eye Drops 5 mg/mL TID	Pazopanib Eye Drops 5 mg/mL QID	Pazopanib Eye Drops 10 mg/mL BID	Pazopanib Eye Drops 10 mg/mL TID	Pazopanib Eye Drops 10 mg/mL QID	Ranibizumab Injections Active Open-label Control Arm	Total
Arm/Group Description	Only the study eye (one eye) per participant enrolled in the study received Placebo QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week treatment period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL TID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL twice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL thrice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL four times daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Participants enrolled in this arm received no eye drops. They received a 0.20 mL to 0.23 mL fill of 10 mg/mL Ranibizumab injection once every four weeks throughout the entire 52 weeks of the study.	Total of all reporting groups
Overall Participants	73	72	74	73	73	72	73	510
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	75.6 (9.42)	74.4 (7.60)	75.1 (8.19)	75.4 (8.42)	75.6 (8.71)	76.2 (8.00)	74.9 (7.27)	75.3 (8.23)
Sex: Female, Male (Count of Participants)
Female	39 53.4%	43 59.7%	42 56.8%	45 61.6%	40 54.8%	46 63.9%	41 56.2%	296 58%
Male	34 46.6%	29 40.3%	32 43.2%	28 38.4%	33 45.2%	26 36.1%	32 43.8%	214 42%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	5 6.8%	4 5.6%	5 6.8%	6 8.2%	5 6.8%	4 5.6%	6 8.2%	35 6.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	1 1.4%	0 0%	0 0%	0 0%	0 0%	0 0%	1 0.2%
White	68 93.2%	67 93.1%	69 93.2%	67 91.8%	68 93.2%	68 94.4%	67 91.8%	474 92.9%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Best-corrected Visual Acuity (BCVA) as Measured by the Number of Letters Read on the Early Treatment of Diabetic Retinopathy Study (ETDRS) Grading Charts at a Starting Distance of 4 Meters at Week 52
Description	BCVA was measured in the study eye using the ETDRS grading charts starting at a test distance of 4 meters. The ETDRS grading chart was of at least 24 to 78 letters. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. There were seven cut off points in change from baseline visual acuity on ETDRS grading chart which are, 15 to 29, 10 to 14, 5 to 9, -4 to 4, -5 to -9, -10 to -14 and -15 to -29 letters. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. If either the baseline or post-randomization value was missing, the change from baseline was set to missing as well. Day 1 values are considered as Baseline in this study.
Time Frame	Day 1 and 52 weeks

Outcome Measure Data

Analysis Population Description

Intent to Treat Population - It consisted of all randomized participants, according to the treatment groups assigned by randomization (i.e., planned rather than the actual treatment regimen), who received at least one dose of study medication. Only participants with data available at the indicated time points were analyzed.

Arm/Group Title	Placebo Control Arm QID	Pazopanib Eye Drops 5 mg/mL TID	Pazopanib Eye Drops 5 mg/mL QID	Pazopanib Eye Drops 10 mg/mL BID	Pazopanib Eye Drops 10 mg/mL TID	Pazopanib Eye Drops 10 mg/mL QID	Ranibizumab Injections Active Open-label Control Arm
Arm/Group Description	Only the study eye (one eye) per participant enrolled in the study received Placebo QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week treatment period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL TID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL twice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL thrice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL four times daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Participants enrolled in this arm received no eye drops. They received a 0.20 mL to 0.23 mL fill of 10 mg/mL Ranibizumab injection once every four weeks throughout the entire 52 weeks of the study.
Measure Participants	73	72	74	73	73	72	73
Least Squares Mean (Standard Error) [Letters]	0.22 (1.006)	1.15 (1.004)	1.81 (0.975)	0.76 (0.995)	0.28 (0.992)	0.62 (1.007)	1.42 (1.020)

2. Secondary Outcome

Title	Percentage of Ranibizumab Re-injections Received Over 28 and 52 Weeks
Description	The investigator interpreted each Week 4 to Week 52 Optical coherence tomography (OCT) scan, BCVA score, and available Fluorescein angiography (FA)/Fundus photography (FP) and re-injected if one or more criteria were met. The criteria were: Evidence of Intraretinal (IR) (with or without cysts) fluid or Subretinal (SR) fluid, a serous retinal pigment epithelial detachment, a notable decline in Visual Acuity, new SR or IR macular hemorrhage that the investigator judges is associated with Choroidal neovascularization, increased lesion size on FA relative to the last angiogram as judged by the investigator or leakage on FA that the investigator judges would benefit from re-injection. Injection rate over 52 weeks was computed by taking the number of injections received divided by the number of visits for the participant. Likewise for 28 weeks it was estimated as the number of post baseline injections received divided by the number of post baseline visits at or before the week 28 visit.
Time Frame	Up to 52 weeks

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Placebo Control Arm QID	Pazopanib Eye Drops 5 mg/mL TID	Pazopanib Eye Drops 5 mg/mL QID	Pazopanib Eye Drops 10 mg/mL BID	Pazopanib Eye Drops 10 mg/mL TID	Pazopanib Eye Drops 10 mg/mL QID
Arm/Group Description	Only the study eye (one eye) per participant enrolled in the study received Placebo QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week treatment period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL TID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL twice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL thrice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL four times daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.
Measure Participants	73	72	74	73	73	72
Injection Rate at 28 Weeks	65.04 (3.418)	55.03 (3.441)	67.92 (3.395)	66.11 (3.418)	61.61 (3.418)	59.42 (3.441)
Overall Injection Rate at 52 weeks	64.24 (3.263)	55.09 (3.286)	65.87 (3.241)	62.50 (3.263)	64.42 (3.263)	58.19 (3.286)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Control Arm QID, Pazopanib Eye Drops 5 mg/mL TID
	Comments	Statistics for Injection Rate at 28 Weeks is presented
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1974
	Comments	Adjusted p-Value has been presented.
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Control Arm QID, Pazopanib Eye Drops 5 mg/mL QID
	Comments	Statistics for Injection Rate at 28 Weeks is presented
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8263
	Comments	Adjusted p-Value has been presented.
	Method	ANOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo Control Arm QID, Pazopanib Eye Drops 10 mg/mL BID
	Comments	Statistics for Injection Rate at 28 Weeks is presented
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8263
	Comments	Adjusted p-Value has been presented.
	Method	ANOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo Control Arm QID, Pazopanib Eye Drops 10 mg/mL TID
	Comments	Statistics for Injection Rate at 28 Weeks is presented
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8263
	Comments	Adjusted p-Value has been presented.
	Method	ANOVA
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo Control Arm QID, Pazopanib Eye Drops 10 mg/mL QID
	Comments	Statistics for Injection Rate at 28 Weeks is presented
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7418
	Comments	Adjusted p-Value has been presented.
	Method	ANOVA
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo Control Arm QID, Pazopanib Eye Drops 5 mg/mL TID
	Comments	Statistics for Overall Injection Rate at 52 weeks is presented
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2429
	Comments	Adjusted p-Value has been presented.
	Method	ANOVA
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo Control Arm QID, Pazopanib Eye Drops 5 mg/mL QID
	Comments	Statistics for Overall Injection Rate at 52 weeks is presented
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9700
	Comments	Adjusted p-Value has been presented.
	Method	ANOVA
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo Control Arm QID, Pazopanib Eye Drops 10 mg/mL BID
	Comments	Statistics for Overall Injection Rate at 52 weeks is presented
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9700
	Comments	Adjusted p-Value has been presented.
	Method	ANOVA
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo Control Arm QID, Pazopanib Eye Drops 10 mg/mL TID
	Comments	Statistics for Overall Injection Rate at 52 weeks is presented
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9700
	Comments	Adjusted p-Value has been presented.
	Method	ANOVA
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo Control Arm QID, Pazopanib Eye Drops 10 mg/mL QID
	Comments	Statistics for Overall Injection Rate at 52 weeks is presented
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7673
	Comments	Adjusted p-Value has been presented.
	Method	ANOVA
	Comments

3. Secondary Outcome

Title	Number of Participants With BCVA Over Time
Description	BCVA was measured in the study eye using the ETDRS grading charts starting at a test distance of 4 meters. The ETDRS grading chart was of at least 24 to 78 letters. There were seven cut off points in change from baseline visual acuity on ETDRS grading chart which are, 15 to 29, 10 to 14, 5 to 9, -4 to 4, -5 to -9, -10 to -14 and -15 to -29 letters.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

Intent to Treat Population. Only participants with data available at the indicated time points were analyzed.

Arm/Group Title	Placebo Control Arm QID	Pazopanib Eye Drops 5 mg/mL TID	Pazopanib Eye Drops 5 mg/mL QID	Pazopanib Eye Drops 10 mg/mL BID	Pazopanib Eye Drops 10 mg/mL TID	Pazopanib Eye Drops 10 mg/mL QID	Ranibizumab Injections Active Open-label Control Arm
Arm/Group Description	Only the study eye (one eye) per participant enrolled in the study received Placebo QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week treatment period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL TID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received 10 mg/mL twice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL thrice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL four times daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Participants enrolled in this arm received no eye drops. They received a 0.20 mL to 0.23 mL fill of 10 mg/mL Ranibizumab injection once every four weeks throughout the entire 52 weeks of the study.
Measure Participants	73	72	74	73	73	72	73
within 5 letters	49 67.1%	49 68.1%	57 77%	57 78.1%	58 79.5%	57 79.2%	62 84.9%
within 10 letters	11 15.1%	15 20.8%	12 16.2%	13 17.8%	12 16.4%	11 15.3%	8 11%
within 15 letters	6 8.2%	5 6.9%	5 6.8%	1 1.4%	3 4.1%	2 2.8%	3 4.1%
more than 15 letters	5 6.8%	2 2.8%	0 0%	1 1.4%	0 0%	1 1.4%	0 0%
within 5 letters	53 72.6%	57 79.2%	65 87.8%	59 80.8%	61 83.6%	60 83.3%	60 82.2%
within 10 letters	16 21.9%	12 16.7%	6 8.1%	12 16.4%	11 15.1%	7 9.7%	11 15.1%
within 15 letters	2 2.7%	2 2.8%	2 2.7%	1 1.4%	1 1.4%	3 4.2%	2 2.7%
more than 15 letters	1 1.4%	0 0%	0 0%	0 0%	0 0%	1 1.4%	0 0%
within 5 letters	34 46.6%	36 50%	51 68.9%	51 69.9%	44 60.3%	47 65.3%	54 74%
within 10 letters	21 28.8%	23 31.9%	18 24.3%	18 24.7%	20 27.4%	16 22.2%	14 19.2%
within 15 letters	11 15.1%	7 9.7%	5 6.8%	1 1.4%	6 8.2%	7 9.7%	4 5.5%
more than 15 letters	5 6.8%	4 5.6%	0 0%	3 4.1%	1 1.4%	1 1.4%	0 0%
within 5 letters	42 57.5%	48 66.7%	60 81.1%	52 71.2%	52 71.2%	55 76.4%	51 69.9%
within 10 letters	19 26%	17 23.6%	10 13.5%	20 27.4%	18 24.7%	11 15.3%	15 20.5%
within 15 letters	9 12.3%	5 6.9%	2 2.7%	1 1.4%	1 1.4%	3 4.2%	5 6.8%
more than 15 letters	2 2.7%	0 0%	1 1.4%	0 0%	0 0%	2 2.8%	1 1.4%
within 5 letters	26 35.6%	25 34.7%	48 64.9%	41 56.2%	35 47.9%	34 47.2%	46 63%
within 10 letters	27 37%	30 41.7%	17 23%	23 31.5%	25 34.2%	24 33.3%	22 30.1%
within 15 letters	13 17.8%	8 11.1%	8 10.8%	4 5.5%	10 13.7%	9 12.5%	2 2.7%
more than 15 letters	5 6.8%	5 6.9%	1 1.4%	4 5.5%	2 2.7%	2 2.8%	0 0%
within 5 letters	36 49.3%	41 56.9%	52 70.3%	46 63%	47 64.4%	49 68.1%	45 61.6%
within 10 letters	23 31.5%	18 25%	18 24.3%	20 27.4%	23 31.5%	16 22.2%	18 24.7%
within 15 letters	9 12.3%	8 11.1%	2 2.7%	4 5.5%	2 2.7%	1 1.4%	6 8.2%
more than 15 letters	4 5.5%	1 1.4%	1 1.4%	1 1.4%	0 0%	3 4.2%	1 1.4%
within 5 letters	24 32.9%	20 27.8%	41 55.4%	36 49.3%	26 35.6%	26 36.1%	35 47.9%
within 10 letters	28 38.4%	37 51.4%	22 29.7%	25 34.2%	29 39.7%	29 40.3%	30 41.1%
within 15 letters	10 13.7%	4 5.6%	9 12.2%	4 5.5%	13 17.8%	11 15.3%	3 4.1%
more than 15 letters	9 12.3%	7 9.7%	1 1.4%	5 6.8%	3 4.1%	3 4.2%	0 0%
within 5 letters	35 47.9%	32 44.4%	47 63.5%	40 54.8%	42 57.5%	43 59.7%	39 53.4%
within 10 letters	24 32.9%	24 33.3%	21 28.4%	25 34.2%	25 34.2%	20 27.8%	19 26%
within 15 letters	9 12.3%	8 11.1%	3 4.1%	4 5.5%	4 5.5%	3 4.2%	7 9.6%
more than 15 letters	4 5.5%	4 5.6%	1 1.4%	1 1.4%	0 0%	3 4.2%	3 4.1%
within 5 letters	21 28.8%	19 26.4%	32 43.2%	32 43.8%	26 35.6%	21 29.2%	30 41.1%
within 10 letters	32 43.8%	36 50%	25 33.8%	26 35.6%	30 41.1%	32 44.4%	31 42.5%
within 15 letters	10 13.7%	5 6.9%	12 16.2%	8 11%	12 16.4%	11 15.3%	5 6.8%
more than 15 letters	6 8.2%	8 11.1%	2 2.7%	4 5.5%	3 4.1%	5 6.9%	1 1.4%
within 5 letters	28 38.4%	28 38.9%	41 55.4%	34 46.6%	32 43.8%	40 55.6%	35 47.9%
within 10 letters	28 38.4%	27 37.5%	25 33.8%	28 38.4%	33 45.2%	23 31.9%	20 27.4%
within 15 letters	10 13.7%	9 12.5%	3 4.1%	4 5.5%	6 8.2%	3 4.2%	8 11%
more than 15 letters	4 5.5%	4 5.6%	1 1.4%	3 4.1%	0 0%	3 4.2%	4 5.5%
within 5 letters	19 26%	16 22.2%	28 37.8%	26 35.6%	23 31.5%	20 27.8%	25 34.2%
within 10 letters	29 39.7%	36 50%	30 40.5%	31 42.5%	34 46.6%	32 44.4%	34 46.6%
within 15 letters	14 19.2%	8 11.1%	12 16.2%	9 12.3%	11 15.1%	11 15.3%	6 8.2%
more than 15 letters	7 9.6%	8 11.1%	2 2.7%	3 4.1%	3 4.1%	6 8.3%	1 1.4%
within 5 letters	27 37%	24 33.3%	36 48.6%	32 43.8%	32 43.8%	36 50%	33 45.2%
within 10 letters	30 41.1%	29 40.3%	29 39.2%	25 34.2%	30 41.1%	25 34.7%	22 30.1%
within 15 letters	8 11%	11 15.3%	5 6.8%	9 12.3%	9 12.3%	3 4.2%	7 9.6%
more than 15 letters	5 6.8%	4 5.6%	1 1.4%	3 4.1%	0 0%	5 6.9%	4 5.5%
within 5 letters	19 26%	13 18.1%	26 35.1%	24 32.9%	22 30.1%	17 23.6%	18 24.7%
within 10 letters	30 41.1%	37 51.4%	29 39.2%	33 45.2%	32 43.8%	33 45.8%	35 47.9%
within 15 letters	14 19.2%	9 12.5%	14 18.9%	9 12.3%	11 15.1%	10 13.9%	10 13.7%
more than 15 letters	5 6.8%	9 12.5%	2 2.7%	3 4.1%	5 6.8%	8 11.1%	3 4.1%
within 5 letters	26 35.6%	24 33.3%	34 45.9%	27 37%	29 39.7%	34 47.2%	31 42.5%
within 10 letters	29 39.7%	30 41.7%	27 36.5%	27 37%	33 45.2%	27 37.5%	22 30.1%
within 15 letters	7 9.6%	10 13.9%	7 9.5%	9 12.3%	7 9.6%	2 2.8%	6 8.2%
more than 15 letters	7 9.6%	4 5.6%	2 2.7%	5 6.8%	1 1.4%	5 6.9%	7 9.6%
within 5 letters	17 23.3%	11 15.3%	23 31.1%	23 31.5%	20 27.4%	14 19.4%	12 16.4%
within 10 letters	32 43.8%	37 51.4%	33 44.6%	32 43.8%	32 43.8%	35 48.6%	38 52.1%
within 15 letters	14 19.2%	11 15.3%	11 14.9%	10 13.7%	12 16.4%	9 12.5%	10 13.7%
more than 15 letters	4 5.5%	9 12.5%	3 4.1%	4 5.5%	4 5.5%	8 11.1%	3 4.1%
within 5 letters	23 31.5%	23 31.9%	30 40.5%	24 32.9%	27 37%	30 41.7%	24 32.9%
within 10 letters	31 42.5%	31 43.1%	31 41.9%	30 41.1%	34 46.6%	26 36.1%	25 34.2%
within 15 letters	8 11%	10 13.9%	5 6.8%	8 11%	4 5.5%	5 6.9%	6 8.2%
more than 15 letters	6 8.2%	4 5.6%	3 4.1%	7 9.6%	3 4.1%	5 6.9%	8 11%
within 5 letters	16 21.9%	10 13.9%	22 29.7%	20 27.4%	19 26%	13 18.1%	12 16.4%
within 10 letters	31 42.5%	36 50%	34 45.9%	34 46.6%	32 43.8%	35 48.6%	41 56.2%
within 15 letters	14 19.2%	11 15.3%	13 17.6%	7 9.6%	15 20.5%	9 12.5%	8 11%
more than 15 letters	4 5.5%	9 12.5%	2 2.7%	7 9.6%	3 4.1%	10 13.9%	2 2.7%
within 5 letters	22 30.1%	19 26.4%	29 39.2%	21 28.8%	25 34.2%	26 36.1%	21 28.8%
within 10 letters	31 42.5%	31 43.1%	32 43.2%	34 46.6%	38 52.1%	32 44.4%	27 37%
within 15 letters	6 8.2%	12 16.7%	6 8.1%	8 11%	3 4.1%	4 5.6%	7 9.6%
more than 15 letters	8 11%	4 5.6%	3 4.1%	5 6.8%	3 4.1%	5 6.9%	8 11%
within 5 letters	14 19.2%	11 15.3%	19 25.7%	20 27.4%	18 24.7%	13 18.1%	12 16.4%
within 10 letters	33 45.2%	32 44.4%	35 47.3%	34 46.6%	34 46.6%	34 47.2%	38 52.1%
within 15 letters	12 16.4%	16 22.2%	14 18.9%	7 9.6%	11 15.1%	9 12.5%	10 13.7%
more than 15 letters	8 11%	9 12.5%	2 2.7%	7 9.6%	5 6.8%	11 15.3%	2 2.7%
within 5 letters	20 27.4%	16 22.2%	23 31.1%	21 28.8%	23 31.5%	25 34.7%	21 28.8%
within 10 letters	31 42.5%	36 50%	37 50%	35 47.9%	35 47.9%	33 45.8%	28 38.4%
within 15 letters	9 12.3%	13 18.1%	6 8.1%	7 9.6%	5 6.8%	3 4.2%	5 6.8%
more than 15 letters	8 11%	3 4.2%	3 4.1%	5 6.8%	4 5.5%	6 8.3%	9 12.3%
within 5 letters	11 15.1%	10 13.9%	18 24.3%	17 23.3%	17 23.3%	13 18.1%	11 15.1%
within 10 letters	36 49.3%	33 45.8%	35 47.3%	32 43.8%	33 45.2%	32 44.4%	38 52.1%
within 15 letters	10 13.7%	16 22.2%	14 18.9%	12 16.4%	12 16.4%	9 12.5%	12 16.4%
more than 15 letters	9 12.3%	9 12.5%	3 4.1%	6 8.2%	5 6.8%	11 15.3%	1 1.4%
within 5 letters	15 20.5%	16 22.2%	22 29.7%	20 27.4%	21 28.8%	25 34.7%	19 26%
within 10 letters	35 47.9%	36 50%	36 48.6%	32 43.8%	36 49.3%	30 41.7%	29 39.7%
within 15 letters	8 11%	12 16.7%	7 9.5%	9 12.3%	6 8.2%	4 5.6%	7 9.6%
more than 15 letters	9 12.3%	4 5.6%	4 5.4%	6 8.2%	4 5.5%	6 8.3%	8 11%
within 5 letters	10 13.7%	9 12.5%	14 18.9%	16 21.9%	15 20.5%	13 18.1%	11 15.1%
within 10 letters	36 49.3%	32 44.4%	37 50%	31 42.5%	36 49.3%	32 44.4%	36 49.3%
within 15 letters	9 12.3%	18 25%	16 21.6%	13 17.8%	12 16.4%	11 15.3%	13 17.8%
more than 15 letters	9 12.3%	8 11.1%	4 5.4%	7 9.6%	5 6.8%	10 13.9%	2 2.7%
within 5 letters	14 19.2%	14 19.4%	20 27%	18 24.7%	21 28.8%	24 33.3%	17 23.3%
within 10 letters	35 47.9%	36 50%	40 54.1%	33 45.2%	38 52.1%	31 43.1%	26 35.6%
within 15 letters	8 11%	12 16.7%	5 6.8%	8 11%	7 9.6%	5 6.9%	10 13.7%
more than 15 letters	8 11%	5 6.9%	5 6.8%	7 9.6%	2 2.7%	6 8.3%	9 12.3%
within 5 letters	11 15.1%	8 11.1%	12 16.2%	15 20.5%	13 17.8%	13 18.1%	10 13.7%
within 10 letters	32 43.8%	31 43.1%	38 51.4%	31 42.5%	37 50.7%	31 43.1%	35 47.9%
within 15 letters	11 15.1%	19 26.4%	15 20.3%	14 19.2%	10 13.7%	8 11.1%	15 20.5%
more than 15 letters	10 13.7%	8 11.1%	6 8.1%	7 9.6%	7 9.6%	12 16.7%	2 2.7%
within 5 letters	13 17.8%	14 19.4%	20 27%	19 26%	18 24.7%	21 29.2%	16 21.9%
within 10 letters	35 47.9%	35 48.6%	39 52.7%	31 42.5%	38 52.1%	33 45.8%	28 38.4%
within 15 letters	8 11%	11 15.3%	5 6.8%	9 12.3%	9 12.3%	5 6.9%	10 13.7%
more than 15 letters	8 11%	6 8.3%	6 8.1%	8 11%	2 2.7%	5 6.9%	7 9.6%

4. Secondary Outcome

Title	Number of Participants Analyzed for Visual Acuity (VA) Response Over Time
Description	VA was measured in the study eye using the ETDRS grading charts starting at a test distance of 4 meters.The ETDRS grading chart was of at least 24 to 78 letters. There were seven cut off points in change from baseline visual acuity on ETDRS grading chart which are, 15 to 29, 10 to 14, 5 to 9, -4 to 4, -5 to -9, -10 to -14 and -15 to -29 letters. This outcome measure contains the number of participants who were analyzed for VA response.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Placebo Control Arm QID	Pazopanib Eye Drops 5 mg/mL TID	Pazopanib Eye Drops 5 mg/mL QID	Pazopanib Eye Drops 10 mg/mL BID	Pazopanib Eye Drops 10 mg/mL TID	Pazopanib Eye Drops 10 mg/mL QID	Ranibizumab Injections Active Open-label Control Arm
Arm/Group Description	Only the study eye (one eye) per participant enrolled in the study received Placebo QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week treatment period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL TID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL twice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL thrice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL four times daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Participants enrolled in this arm received no eye drops. They received a 0.20 mL to 0.23 mL fill of 10 mg/mL Ranibizumab injection once every four weeks throughout the entire 52 weeks of the study.
Measure Participants	73	72	74	73	73	72	73
Count of Participants [Participants]	25 34.2%	19 26.4%	20 27%	18 24.7%	21 28.8%	23 31.9%	15 20.5%

5. Secondary Outcome

Title	Change From Baseline in Center Point Thickness (CPT) Over Time
Description	CPT was the inner limiting membrane to the beginning of the retinal pigment epithelium (RPE) inclusive of SR fluid. The outer boundary included the outer segment of the photoreceptors and not included the RPE. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. If either the baseline or post-randomization value was missing, the change from baseline was set to missing as well. Day 1 values are considered as Baseline in this study. In amendment 3, inclusion criterion number 5 was revised to remove the required quantitative OCT component. OCT examination was used to supplement FA findings and provided qualitative (presence of SR and/or IR fluid) and quantitative (a CPT that is at least 250 microns) evidence of an active subfoveal lesion. Hence data for pre and post amendment have been provided separately.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Placebo Control Arm QID	Pazopanib Eye Drops 5 mg/mL TID	Pazopanib Eye Drops 5 mg/mL QID	Pazopanib Eye Drops 10 mg/mL BID	Pazopanib Eye Drops 10 mg/mL TID	Pazopanib Eye Drops 10 mg/mL QID	Ranibizumab Injections Active Open-label Control Arm
Arm/Group Description	Only the study eye (one eye) per participant enrolled in the study received Placebo QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week treatment period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL TID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL twice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL thrice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL four times daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Participants enrolled in this arm received no eye drops. They received a 0.20 mL to 0.23 mL fill of 10 mg/mL Ranibizumab injection once every four weeks throughout the entire 52 weeks of the study.
Measure Participants	73	72	74	73	73	72	73
Subgroup-Genotype, Week 28, CC	10.0 (55.29)	12.3 (48.05)	3.4 (56.23)	-27.6 (136.79)	16.6 (75.36)	9.7 (76.41)	-10.4 (79.28)
Subgroup-Genotype, Week 28, CT	9.6 (77.04)	11.1 (62.94)	9.4 (84.10)	-8.9 (54.05)	-8.4 (87.97)	4.2 (72.25)	-18.1 (101.47)
Subgroup-Genotype, Week 52, CC	12.7 (76.07)	6.9 (63.99)	3.6 (95.68)	-37.3 (118.33)	31.4 (56.63)	7.4 (93.46)	-40.8 (72.12)
Subgroup-Genotype, Week 52, CT	-2.9 (48.00)	5.5 (73.67)	-10.5 (65.41)	-9.7 (61.55)	-12.3 (101.63)	-7.2 (89.75)	-14.2 (108.24)
Subgroup-Pre-amendment 3, Week 28	20.9 (104.87)	30.8 (75.58)	-15.9 (64.65)	-44.4 (114.54)	27.8 (113.06)	-28.5 (101.42)	-16.6 (89.64)
Subgroup-Post-amendment 3, Week 28	9.9 (72.13)	11.0 (53.06)	8.5 (65.28)	-8.6 (92.03)	-7.7 (66.09)	14.1 (65.43)	-15.0 (87.50)
Subgroup-Pre-amendment 3, Week 52	-24.1 (66.83)	13.8 (120.91)	-57.8 (85.39)	-50.3 (63.87)	-8.2 (56.80)	-9.0 (142.59)	-29.0 (91.44)
Subgroup-Post-amendment 3, Week 52	0.1 (64.33)	9.6 (61.19)	2.2 (74.83)	-13.7 (97.67)	3.2 (86.08)	-3.0 (67.15)	-23.5 (90.13)

6. Secondary Outcome

Title	Number of Participants That Met Criteria for Re-injection
Description	The investigator interpreted each Week 4 to Week 52 Optical coherence tomography (OCT) scan, BCVA score, and available Fluorescein angiography (FA)/Fundus photography (FP) and re-injected if one or more criteria were met. The criteria were: Evidence of Intraretinal (IR) (with or without cysts) fluid or Subretinal (SR) fluid, a serous retinal pigment epithelial detachment, a notable decline in Visual Acuity, new SR or IR macular hemorrhage that the investigator judges is associated with Choroidal neovascularization, increased lesion size on FA relative to the last angiogram as judged by the investigator or leakage on FA that the investigator judges would benefit from re-injection.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Placebo Control Arm QID	Pazopanib Eye Drops 5 mg/mL TID	Pazopanib Eye Drops 5 mg/mL QID	Pazopanib Eye Drops 10 mg/mL BID	Pazopanib Eye Drops 10 mg/mL TID	Pazopanib Eye Drops 10 mg/mL QID
Arm/Group Description	Only the study eye (one eye) per participant enrolled in the study received Placebo QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week treatment period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL TID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL twice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL thrice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL four times daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.
Measure Participants	73	72	74	73	73	72
Week 4	49 67.1%	33 45.8%	54 73%	48 65.8%	45 61.6%	44 61.1%
Week 12	45 61.6%	40 55.6%	49 66.2%	47 64.4%	46 63%	42 58.3%
Week 16	1 1.4%	0 0%	0 0%	0 0%	0 0%	0 0%
Week 20	0 0%	0 0%	0 0%	1 1.4%	0 0%	0 0%
Week 28	38 52.1%	41 56.9%	45 60.8%	47 64.4%	39 53.4%	36 50%
Week 32	0 0%	0 0%	0 0%	1 1.4%	0 0%	1 1.4%
Week 44	0 0%	1 1.4%	0 0%	0 0%	0 0%	0 0%
Week 52	36 49.3%	28 38.9%	43 58.1%	37 50.7%	45 61.6%	36 50%

7. Secondary Outcome

Title	Change From Baseline in the Area of Choroidal Neovascularisation (CNV)
Description	Choroidal neovascularisation is progressive worsening of vision that can cause hemorrhage and exudation, and finally disciform scarring and retinal atrophy. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. If either the baseline or post-randomization value was missing, the change from baseline was set to missing as well. Day 1 values are considered as Baseline in this study.
Time Frame	Day 1, Week 28 and Week 52

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Placebo Control Arm QID	Pazopanib Eye Drops 5 mg/mL TID	Pazopanib Eye Drops 5 mg/mL QID	Pazopanib Eye Drops 10 mg/mL BID	Pazopanib Eye Drops 10 mg/mL TID	Pazopanib Eye Drops 10 mg/mL QID	Ranibizumab Injections Active Open-label Control Arm
Arm/Group Description	Only the study eye (one eye) per participant enrolled in the study received Placebo QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week treatment period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL TID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL twice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL thrice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL four times daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Participants enrolled in this arm received no eye drops. They received a 0.20 mL to 0.23 mL fill of 10 mg/mL Ranibizumab injection once every four weeks throughout the entire 52 weeks of the study.
Measure Participants	73	72	74	73	73	72	73
Week 28	0.10 (0.113)	0.16 (0.114)	0.09 (0.111)	0.06 (0.114)	-0.05 (0.112)	0.13 (0.114)	-0.08 (0.118)
Week 52	0.10 (0.134)	0.13 (0.133)	0.08 (0.129)	-0.16 (0.134)	-0.10 (0.132)	0.13 (0.134)	-0.08 (0.137)

8. Secondary Outcome

Title	Change From Baseline in the Area of the CNV Lesion Complex (i.e. CNV, Blood, PED, and Fibrosis)
Description	CNV is progressive worsening of vision that can cause hemorrhage and exudation, and finally disciform scarring and retinal atrophy. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. If either the baseline or post-randomization value was missing, the change from baseline was set to missing as well. Day 1 values are considered as Baseline in this study.
Time Frame	Day 1, Week 28 and Week 52

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Placebo Control Arm QID	Pazopanib Eye Drops 5 mg/mL TID	Pazopanib Eye Drops 5 mg/mL QID	Pazopanib Eye Drops 10 mg/mL BID	Pazopanib Eye Drops 10 mg/mL TID	Pazopanib Eye Drops 10 mg/mL QID	Ranibizumab Injections Active Open-label Control Arm
Arm/Group Description	Only the study eye (one eye) per participant enrolled in the study received Placebo QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week treatment period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL TID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL twice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL thrice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL four times daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Participants enrolled in this arm received no eye drops. They received a 0.20 mL to 0.23 mL fill of 10 mg/mL Ranibizumab injection once every four weeks throughout the entire 52 weeks of the study.
Measure Participants	73	72	74	73	73	72	73
Week 28	0.18 (0.131)	0.32 (0.132)	0.23 (0.129)	0.12 (0.132)	0.00 (0.130)	0.13 (0.132)	-0.13 (0.137)
Week 52	0.40 (0.152)	0.51 (0.151)	0.09 (0.146)	0.01 (0.151)	-0.05 (0.150)	0.20 (0.152)	-0.11 (0.155)

9. Secondary Outcome

Title	Change From Baseline in the Area of Fluorescein Leakage
Description	Fluorescein angiograms was performed at the Screening, Week 12, Week 28, and Week 52 Visits. All images, including any that were performed at the investigator's medical discretion, were transferred to the FPRC. Fluorescein was injected intravenously according to usual clinic procedures. Dose response was also examined under different aspects of re-injection, such as time to first injection, the percentage of participants that required an injection by Week 28, as well as the estimation of the probability of reinjection. FA assessments of area of fluorescein leakage, CNV area and area of CNV lesion complex were also examined for dose differentiation.
Time Frame	Day 1, Week 28 and Week 52

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Placebo Control Arm QID	Pazopanib Eye Drops 5 mg/mL TID	Pazopanib Eye Drops 5 mg/mL QID	Pazopanib Eye Drops 10 mg/mL BID	Pazopanib Eye Drops 10 mg/mL TID	Pazopanib Eye Drops 10 mg/mL QID	Ranibizumab Injections Active Open-label Control Arm
Arm/Group Description	Only the study eye (one eye) per participant enrolled in the study received Placebo QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week treatment period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL TID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL twice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL thrice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL four times daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Participants enrolled in this arm received no eye drops. They received a 0.20 mL to 0.23 mL fill of 10 mg/mL Ranibizumab injection once every four weeks throughout the entire 52 weeks of the study.
Measure Participants	73	72	74	73	73	72	73
Week 28	-0.33 (0.150)	-0.27 (0.151)	-0.32 (0.148)	-0.40 (0.151)	-0.61 (0.149)	-0.33 (0.151)	-0.60 (0.156)
Week 52	-0.40 (0.177)	-0.45 (0.176)	-0.19 (0.171)	-0.77 (0.177)	-0.57 (0.175)	-0.37 (0.178)	-0.66 (0.181)

10. Secondary Outcome

Title	Change in Area of Serous Sensory Retinal Detachment (SSRD)
Description	This is an Optical coherence tomography (OCT) parameter used to manually measure thickness along any scan. OCT was performed at week 28 and week 52.
Time Frame	Day 1, Week 28 and Week 52

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Placebo Control Arm QID	Pazopanib Eye Drops 5 mg/mL TID	Pazopanib Eye Drops 5 mg/mL QID	Pazopanib Eye Drops 10 mg/mL BID	Pazopanib Eye Drops 10 mg/mL TID	Pazopanib Eye Drops 10 mg/mL QID	Ranibizumab Injections Active Open-label Control Arm
Arm/Group Description	Only the study eye (one eye) per participant enrolled in the study received Placebo QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week treatment period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL TID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL twice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL thrice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL four times daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Participants enrolled in this arm received no eye drops. They received a 0.20 mL to 0.23 mL fill of 10 mg/mL Ranibizumab injection once every four weeks throughout the entire 52 weeks of the study.
Measure Participants	73	72	74	73	73	72	73
Week 28	-0.30 (0.259)	-0.28 (0.264)	-0.14 (0.255)	-0.55 (0.261)	-0.64 (0.261)	-0.46 (0.264)	-0.95 (0.273)
Week 52	-0.52 (0.317)	-0.76 (0.315)	-0.79 (0.300)	-1.24 (0.312)	-1.17 (0.321)	-0.83 (0.321)	-1.02 (0.322)

11. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect.
Time Frame	Up to 52 Weeks

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Placebo Control Arm QID	Pazopanib Eye Drops 5 mg/mL TID	Pazopanib Eye Drops 5 mg/mL QID	Pazopanib Eye Drops 10 mg/mL BID	Pazopanib Eye Drops 10 mg/mL TID	Pazopanib Eye Drops 10 mg/mL QID	Ranibizumab Injections Active Open-label Control Arm
Arm/Group Description	Only the study eye (one eye) per participant enrolled in the study received Placebo QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week treatment period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL TID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL twice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL thrice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL four times daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Participants enrolled in this arm received no eye drops. They received a 0.20 mL to 0.23 mL fill of 10 mg/mL Ranibizumab injection once every four weeks throughout the entire 52 weeks of the study.
Measure Participants	73	72	74	73	73	72	73
Adverse Events (AEs)	11 15.1%	10 13.9%	12 16.2%	11 15.1%	10 13.7%	11 15.3%	6 8.2%
Serious Adverse Events (SAEs)	52 71.2%	34 47.2%	47 63.5%	44 60.3%	46 63%	41 56.9%	42 57.5%

12. Secondary Outcome

Title	Summary of Potentially Clinically Important Findings for Ophthalmic Examinations
Description	Opthalmicexaminations were done on Ocular alignment and motility, pupillary function, and visual fields by confrontation. Slit-lamp biomicroscopic examination of the anterior segment structure was performed. Fundus slit-lamp biomicroscopic examination, including use of accessory diagnostic lenses, to view the vitreous, retina (including posterior pole and periphery), macula, vasculature, and optic nerve was also performed. These examinations were performed on the study eye (SE) and the Fellow eye (FE). Participants with abnormal findings are listed here.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Placebo Control Arm QID	Pazopanib Eye Drops 5 mg/mL TID	Pazopanib Eye Drops 5 mg/mL QID	Pazopanib Eye Drops 10 mg/mL BID	Pazopanib Eye Drops 10 mg/mL TID	Pazopanib Eye Drops 10 mg/mL QID	Ranibizumab Injections Active Open-label Control Arm
Arm/Group Description	Only the study eye (one eye) per participant enrolled in the study received Placebo QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week treatment period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL TID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL twice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL thrice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL four times daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Participants enrolled in this arm received no eye drops. They received a 0.20 mL to 0.23 mL fill of 10 mg/mL Ranibizumab injection once every four weeks throughout the entire 52 weeks of the study.
Measure Participants	73	72	74	73	73	72	73
Afferent papillary defect present, SE	4 5.5%	2 2.8%	4 5.4%	2 2.7%	1 1.4%	2 2.8%	3 4.1%
Afferent papillary defect present, FE	4 5.5%	1 1.4%	5 6.8%	2 2.7%	3 4.1%	2 2.8%	3 4.1%
Eye motility abnormal, SE	1 1.4%	0 0%	0 0%	1 1.4%	0 0%	0 0%	1 1.4%
Eye motility abnormal, FE	1 1.4%	0 0%	0 0%	0 0%	0 0%	1 1.4%	0 0%
Confrontation visual field abnormal, SE	2 2.7%	1 1.4%	0 0%	0 0%	0 0%	1 1.4%	0 0%
Confrontation visual field abnormal, FE	2 2.7%	0 0%	2 2.7%	1 1.4%	2 2.7%	0 0%	2 2.7%
Ptosis present, SE	2 2.7%	1 1.4%	1 1.4%	0 0%	8 11%	2 2.8%	2 2.7%
Ptosis present, FE	1 1.4%	3 4.2%	1 1.4%	1 1.4%	9 12.3%	2 2.8%	3 4.1%
2-step worsening of Meibomian gland dysfunction,SE	0 0%	0 0%	2 2.7%	0 0%	2 2.7%	0 0%	0 0%
2-step worsening of Meibomian gland dysfunction,FE	0 0%	0 0%	4 5.4%	0 0%	2 2.7%	0 0%	0 0%
2-step worsening of Conjunctival injection, SE	2 2.7%	0 0%	1 1.4%	0 0%	1 1.4%	5 6.9%	0 0%
2-step worsening of Conjunctival injection, FE	1 1.4%	1 1.4%	1 1.4%	1 1.4%	1 1.4%	3 4.2%	1 1.4%
2-step worsening of Chemosis, SE	0 0%	0 0%	0 0%	0 0%	1 1.4%	1 1.4%	0 0%
2-step worsening of Chemosis, FE	0 0%	0 0%	0 0%	0 0%	1 1.4%	1 1.4%	0 0%
2-step worsening of punctate keratopathy, SE	0 0%	0 0%	1 1.4%	0 0%	2 2.7%	4 5.6%	0 0%
2-step worsening of punctate keratopathy, FE	0 0%	1 1.4%	2 2.7%	0 0%	1 1.4%	0 0%	2 2.7%
2-step worsening of epithelial edema, SE	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
2-step worsening of epithelial edema, FE	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Abnormal postbaseline finding of active opacity,SE	1 1.4%	0 0%	3 4.1%	0 0%	1 1.4%	0 0%	0 0%
Abnormal postbaseline finding of active opacity,FE	2 2.7%	0 0%	3 4.1%	0 0%	2 2.7%	0 0%	0 0%
Abnormal post-baseline finding of active edema, SE	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Abnormal post-baseline finding of active edema, FE	1 1.4%	0 0%	0 0%	1 1.4%	0 0%	0 0%	0 0%
Grade 1+ of Anterior chamber cell, SE	0 0%	1 1.4%	0 0%	1 1.4%	1 1.4%	0 0%	1 1.4%
Grade 1+ of Anterior chamber cell, FE	1 1.4%	1 1.4%	0 0%	1 1.4%	0 0%	0 0%	1 1.4%
Anterior chamber hypopyon present, SE	0 0%	1 1.4%	0 0%	0 0%	0 0%	0 0%	0 0%
Anterior chamber hypopyon present, FE	0 0%	0 0%	2 2.7%	2 2.7%	0 0%	0 0%	0 0%
Grade 2+ of Anterior chamber flare, SE	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Grade 2+ of Anterior chamber flare, FE	0 0%	0 0%	0 0%	1 1.4%	0 0%	0 0%	0 0%
2+ increases in Any Lens Opacity, SE	4 5.5%	1 1.4%	5 6.8%	6 8.2%	5 6.8%	7 9.7%	6 8.2%
2+ increases in Any Lens Opacity, FE	3 4.1%	1 1.4%	4 5.4%	4 5.5%	4 5.5%	4 5.6%	6 8.2%
VA =>15 loss from Baseline or Previous Visit, SE	15 20.5%	8 11.1%	7 9.5%	9 12.3%	9 12.3%	16 22.2%	5 6.8%
VA =>15 loss from Baseline or Previous Visit, FE	10 13.7%	5 6.9%	6 8.1%	10 13.7%	5 6.8%	5 6.9%	6 8.2%

13. Secondary Outcome

Title	Summary of Intraocular Pressure Exam Findings
Description	Intraocular pressure (IOP) measurement was done with Goldmann tonometer. Intraocular pressure was measured prior to dilating the pupil and, to account for diurnal variation, at approximately the same time of day for every visit.
Time Frame	Up to week 52

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Placebo Control Arm QID	Pazopanib Eye Drops 5 mg/mL TID	Pazopanib Eye Drops 5 mg/mL QID	Pazopanib Eye Drops 10 mg/mL BID	Pazopanib Eye Drops 10 mg/mL TID	Pazopanib Eye Drops 10 mg/mL QID	Ranibizumab Injections Active Open-label Control Arm
Arm/Group Description	Only the study eye (one eye) per participant enrolled in the study received Placebo QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week treatment period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL TID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL twice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL thrice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL four times daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Participants enrolled in this arm received no eye drops. They received a 0.20 mL to 0.23 mL fill of 10 mg/mL Ranibizumab injection once every four weeks throughout the entire 52 weeks of the study.
Measure Participants	73	72	74	73	73	72	73
Any post-baseline IOP >=30 study eye	0 0%	0 0%	1 1.4%	1 1.4%	0 0%	1 1.4%	1 1.4%
IOP Lowering Medication for study eye	1 1.4%	4 5.6%	5 6.8%	6 8.2%	4 5.5%	3 4.2%	6 8.2%
IOP Lowering procedure for study eye	1 1.4%	1 1.4%	0 0%	0 0%	0 0%	0 0%	0 0%
Any post-baseline IOP >=30 fellow eye	0 0%	0 0%	0 0%	1 1.4%	0 0%	0 0%	2 2.7%
IOP Lowering Medication for fellow eye	2 2.7%	3 4.2%	3 4.1%	5 6.8%	1 1.4%	2 2.8%	4 5.5%
IOP Lowering procedure for fellow eye	1 1.4%	1 1.4%	1 1.4%	0 0%	0 0%	0 0%	0 0%

14. Secondary Outcome

Title	Number of Participants With Vital Sign Values Outside of Clinical Concern Range
Description	Vital signs including systolic and diastolic blood pressure and heart rate were measured throughout the study. Number of participants with vital signs outside of clinical concern Range were summarized. 'High' denotes above normal range and 'Low' denotes below normal range for all the categories. The potential clinical importance ranges (low and high) of the vital sign parameters were for systolic blood pressure (<85 and >160 millimeter of mercury [mmHg]), diastolic blood pressure (<45 and >100 mmHg) and heart rate (<40 and >110 beats per minute). Only those parameters for which at least one value of potential clinical importance was reported are summarized. The number of participants with potential clinical important vital parameter findings at any visit were reported.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

Safety Population. Only participants with data available at the indicated time points were analyzed.

Arm/Group Title	Placebo Control Arm QID	Pazopanib Eye Drops 5 mg/mL TID	Pazopanib Eye Drops 5 mg/mL QID	Pazopanib Eye Drops 10 mg/mL BID	Pazopanib Eye Drops 10 mg/mL TID	Pazopanib Eye Drops 10 mg/mL QID	Ranibizumab Injections Active Open-label Control Arm
Arm/Group Description	Only the study eye (one eye) per participant enrolled in the study received Placebo QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week treatment period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL TID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL twice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL thrice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL four times daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Participants enrolled in this arm received no eye drops. They received a 0.20 mL to 0.23 mL fill of 10 mg/mL Ranibizumab injection once every four weeks throughout the entire 52 weeks of the study.
Measure Participants	73	72	74	73	73	72	73
Average diastolic blood pressure, Week 4, High	0 0%	0 0%	0 0%	0 0%	1 1.4%	0 0%	0 0%
Average diastolic blood pressure, Week 4, Low	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.4%
Average diastolic blood pressure, Week 8, High	1 1.4%	0 0%	0 0%	0 0%	1 1.4%	1 1.4%	0 0%
Average diastolic blood pressure, Week 12, High	1 1.4%	0 0%	1 1.4%	0 0%	0 0%	2 2.8%	1 1.4%
Average diastolic blood pressure, Week 16, High	0 0%	0 0%	0 0%	0 0%	1 1.4%	0 0%	0 0%
Average diastolic blood pressure, Week 20, High	0 0%	0 0%	0 0%	0 0%	1 1.4%	0 0%	0 0%
Average diastolic blood pressure, Week 24, High	0 0%	0 0%	1 1.4%	0 0%	1 1.4%	1 1.4%	0 0%
Average diastolic blood pressure, Week 24, Low	0 0%	0 0%	0 0%	1 1.4%	0 0%	0 0%	0 0%
Average diastolic blood pressure, Week 28, Low	0 0%	0 0%	0 0%	1 1.4%	0 0%	0 0%	0 0%
Average diastolic blood pressure, Week 32, High	1 1.4%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Average diastolic blood pressure, Week 36, Low	0 0%	0 0%	0 0%	2 2.7%	0 0%	0 0%	1 1.4%
Average diastolic blood pressure, Week 44, High	1 1.4%	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.4%
Average diastolic blood pressure, Week 48, High	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.4%	0 0%
Average diastolic blood pressure, Week 52, High	0 0%	0 0%	1 1.4%	0 0%	0 0%	0 0%	0 0%
Average systolic blood pressure, Day 1, High	0 0%	1 1.4%	0 0%	0 0%	0 0%	0 0%	2 2.7%
Average systolic blood pressure, Week 4, High	0 0%	0 0%	0 0%	0 0%	1 1.4%	1 1.4%	0 0%
Average systolic blood pressure, Week 8, High	0 0%	1 1.4%	0 0%	1 1.4%	0 0%	1 1.4%	1 1.4%
Average systolic blood pressure, Week 12, High	0 0%	0 0%	0 0%	2 2.7%	1 1.4%	5 6.9%	2 2.7%
Average systolic blood pressure, Week 16, High	0 0%	1 1.4%	0 0%	1 1.4%	2 2.7%	1 1.4%	2 2.7%
Average systolic blood pressure, Week 20, High	1 1.4%	0 0%	3 4.1%	0 0%	3 4.1%	1 1.4%	1 1.4%
Average systolic blood pressure, Week 24, High	0 0%	0 0%	3 4.1%	1 1.4%	3 4.1%	1 1.4%	2 2.7%
Average systolic blood pressure, Week 28, High	1 1.4%	0 0%	0 0%	5 6.8%	1 1.4%	3 4.2%	5 6.8%
Average systolic blood pressure, Week 32, High	0 0%	0 0%	2 2.7%	0 0%	1 1.4%	2 2.8%	0 0%
Average systolic blood pressure, Week 36, High	1 1.4%	0 0%	2 2.7%	2 2.7%	0 0%	2 2.8%	1 1.4%
Average systolic blood pressure, Week 40, High	1 1.4%	0 0%	2 2.7%	1 1.4%	0 0%	1 1.4%	1 1.4%
Average systolic blood pressure, Week 44, High	2 2.7%	0 0%	0 0%	1 1.4%	2 2.7%	0 0%	0 0%
Average systolic blood pressure, Week 44, Low	1 1.4%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Average systolic blood pressure, Week 48, High	1 1.4%	0 0%	0 0%	0 0%	0 0%	1 1.4%	2 2.7%
Average systolic blood pressure, Week 52, High	2 2.7%	2 2.8%	2 2.7%	1 1.4%	2 2.7%	2 2.8%	2 2.7%
Heart Rate, Week 16, High	0 0%	1 1.4%	0 0%	0 0%	0 0%	0 0%	0 0%
Heart Rate, Week 20, High	0 0%	1 1.4%	0 0%	1 1.4%	0 0%	1 1.4%	0 0%
Heart Rate, Week 24, High	0 0%	1 1.4%	0 0%	0 0%	0 0%	0 0%	0 0%
Heart Rate, Week 32, High	0 0%	0 0%	0 0%	1 1.4%	0 0%	0 0%	0 0%
Heart Rate, Week 36, High	1 1.4%	1 1.4%	0 0%	0 0%	0 0%	0 0%	0 0%
Heart Rate, Week 40, High	0 0%	1 1.4%	0 0%	0 0%	0 0%	0 0%	0 0%
Heart Rate, Week 48, High	0 0%	1 1.4%	0 0%	0 0%	0 0%	0 0%	0 0%

15. Secondary Outcome

Title	Summary of Abnormal Electrocardiogram (ECG) Findings
Description	12-Lead ECGs were performed in triplicate and were obtained on Weeks 4 to Week 28 and Week 52. The on-treatment ECGs were used to ascertain any risk of QTc interval prolongation at extremely low pazopanib exposures compared to what was routinely observed in participants with cancer. The on-treatment ECG data collected from participants assigned to one of the control arms also provided ECG background rate data for participants not exposed to pazopanib. Participants with Clinically significant abnormal ECGs are included here.
Time Frame	Week 4, Week 28, Week 44 and Week 52

Outcome Measure Data

Analysis Population Description

Safety population. Only participants with data available at the indicated time points were analyzed.

Arm/Group Title	Placebo Control Arm QID	Pazopanib Eye Drops 5 mg/mL TID	Pazopanib Eye Drops 5 mg/mL QID	Pazopanib Eye Drops 10 mg/mL BID	Pazopanib Eye Drops 10 mg/mL TID	Pazopanib Eye Drops 10 mg/mL QID	Ranibizumab Injections Active Open-label Control Arm
Arm/Group Description	Only the study eye (one eye) per participant enrolled in the study received Placebo QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week treatment period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL TID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL twice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL thrice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL four times daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Participants enrolled in this arm received no eye drops. They received a 0.20 mL to 0.23 mL fill of 10 mg/mL Ranibizumab injection once every four weeks throughout the entire 52 weeks of the study.
Measure Participants	73	72	74	73	73	72	73
Week 4, Abnormal - Clinically significant	10 13.7%	11 15.3%	13 17.6%	10 13.7%	13 17.8%	17 23.6%	15 20.5%
Week 4, Abnormal - Not Clinically significant	24 32.9%	25 34.7%	25 33.8%	25 34.2%	24 32.9%	31 43.1%	27 37%
Week 28, Abnormal - Clinically significant	10 13.7%	8 11.1%	9 12.2%	10 13.7%	7 9.6%	7 9.7%	16 21.9%
Week 28, Abnormal - Not Clinically significant	21 28.8%	22 30.6%	17 23%	22 30.1%	18 24.7%	25 34.7%	18 24.7%
Week 44, Abnormal - Clinically significant	0 0%	1 1.4%
Week 44, Abnormal - Not Clinically significant	1 1.4%	0 0%
Week 52, Abnormal - Clinically significant	11 15.1%	5 6.9%	11 14.9%	10 13.7%	8 11%	9 12.5%	10 13.7%
Week 52, Abnormal - Not Clinically significant	23 31.5%	29 40.3%	25 33.8%	21 28.8%	24 32.9%	22 30.6%	20 27.4%

16. Secondary Outcome

Title	Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern
Description	The Laboratory Parameters included Alanine Amino Transferase (ALT), Albumin, Alkaline Phosphatase, Aspartate Amino Transferase (AST), Calcium, Bicarbonate, Creatinine, Glucose, Hemoglobin, Lymphocytes, Platelet count, Potassium, Sodium, Thyroid Stimulating Hormone (TSH), Total Bilirubin, Total Neutrophils, Blood Urea Nitrogen (BUN) and White Blood Cell count (WBC). Number of participants with Laboratory outside of clinical concern Range were summarized here. Data of high and low from the clinical concern range has been provided here. Here 'High' denotes above normal range and 'Low' denotes below normal range for all the categories.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

Safety Population. Only participants with data available at the indicated time points were analyzed.

Arm/Group Title	Placebo Control Arm QID	Pazopanib Eye Drops 5 mg/mL TID	Pazopanib Eye Drops 5 mg/mL QID	Pazopanib Eye Drops 10 mg/mL BID	Pazopanib Eye Drops 10 mg/mL TID	Pazopanib Eye Drops 10 mg/mL QID	Ranibizumab Injections Active Open-label Control Arm
Arm/Group Description	Only the study eye (one eye) per participant enrolled in the study received Placebo QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week treatment period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL TID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL twice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL thrice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL four times daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Participants enrolled in this arm received no eye drops. They received a 0.20 mL to 0.23 mL fill of 10 mg/mL Ranibizumab injection once every four weeks throughout the entire 52 weeks of the study.
Measure Participants	73	72	74	73	73	72	73
ALT, Week 4, High	0 0%	0 0%	2 2.7%	0 0%	0 0%	0 0%	0 0%
ALT, Week 8, High	0 0%	0 0%	0 0%	1 1.4%	0 0%	0 0%	0 0%
ALT, Week 12, High	0 0%	0 0%	0 0%	1 1.4%	0 0%	0 0%	0 0%
ALT, Week 52, High	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.4%
Albumin, Week 4, Low	1 1.4%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Alkaline Phosphatase, Week 12, High	1 1.4%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Alkaline Phosphatase, Week 16, High	1 1.4%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Alkaline Phosphatase, Week 20, High	1 1.4%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Alkaline Phosphatase, Week 24, High	1 1.4%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
AST, Week 8, High	0 0%	0 0%	0 0%	1 1.4%	0 0%	0 0%	0 0%
AST, Week 12, High	0 0%	0 0%	0 0%	1 1.4%	0 0%	0 0%	0 0%
AST, Week 16, High	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.4%	0 0%
AST, Week 20, High	0 0%	1 1.4%	0 0%	0 0%	0 0%	0 0%	1 1.4%
AST, Week 48, High	0 0%	1 1.4%	0 0%	0 0%	0 0%	0 0%	0 0%
Calcium, Day 1, High	2 2.7%	1 1.4%	0 0%	0 0%	0 0%	0 0%	0 0%
Calcium, Week 4, High	1 1.4%	0 0%	0 0%	1 1.4%	1 1.4%	0 0%	0 0%
Calcium, Week 12, High	2 2.7%	0 0%	0 0%	0 0%	1 1.4%	0 0%	0 0%
Calcium, Week 28, High	1 1.4%	0 0%	0 0%	0 0%	1 1.4%	0 0%	0 0%
Calcium, Week 52, Low	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.4%	0 0%
Bicarbonate, Day 1, High	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.4%	0 0%
Bicarbonate, Week4, Low	1 1.4%	0 0%	1 1.4%	0 0%	1 1.4%	2 2.8%	2 2.7%
Bicarbonate, Week 8, Low	0 0%	1 1.4%	0 0%	1 1.4%	0 0%	0 0%	0 0%
Bicarbonate, Week 12, Low	0 0%	1 1.4%	1 1.4%	1 1.4%	2 2.7%	1 1.4%	1 1.4%
Bicarbonate, Week 28, Low	3 4.1%	1 1.4%	0 0%	0 0%	0 0%	4 5.6%	1 1.4%
Bicarbonate, Week 32, Low	1 1.4%	1 1.4%	0 0%	0 0%	0 0%	0 0%	0 0%
Bicarbonate, Week 40, Low	0 0%	1 1.4%	1 1.4%	1 1.4%	0 0%	1 1.4%	1 1.4%
Bicarbonate, Week 52, Low	1 1.4%	3 4.2%	1 1.4%	2 2.7%	1 1.4%	2 2.8%	2 2.7%
Creatinine, Day 1, High	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.4%	0 0%
Creatinine, Week 4, High	1 1.4%	0 0%	0 0%	0 0%	0 0%	1 1.4%	0 0%
Creatinine, Week 12, High	0 0%	0 0%	0 0%	1 1.4%	1 1.4%	1 1.4%	0 0%
Creatinine, Week 28, High	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	2 2.7%
Creatinine, Week 52, High	0 0%	1 1.4%	0 0%	1 1.4%	0 0%	1 1.4%	0 0%
Glucose, Day 1, High	6 8.2%	5 6.9%	3 4.1%	3 4.1%	1 1.4%	3 4.2%	7 9.6%
Glucose, Day 1, Low	0 0%	0 0%	1 1.4%	0 0%	0 0%	1 1.4%	0 0%
Glucose, Week 4, High	2 2.7%	3 4.2%	3 4.1%	4 5.5%	2 2.7%	2 2.8%	3 4.1%
Glucose, Week 4, Low	0 0%	1 1.4%	2 2.7%	0 0%	0 0%	1 1.4%	2 2.7%
Glucose, Week 8, High	0 0%	0 0%	0 0%	1 1.4%	0 0%	0 0%	0 0%
Glucose, Week 12, High	3 4.1%	5 6.9%	3 4.1%	2 2.7%	4 5.5%	2 2.8%	8 11%
Glucose, Week 12, Low	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.4%
Glucose, Week 28, High	3 4.1%	4 5.6%	3 4.1%	4 5.5%	1 1.4%	0 0%	6 8.2%
Glucose, Week 28, Low	0 0%	0 0%	0 0%	0 0%	1 1.4%	0 0%	0 0%
Glucose, Week 32, High	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.4%	0 0%
Glucose, Week 36, High	0 0%	1 1.4%
Glucose, Week 40, High	6 8.2%	7 9.7%	4 5.4%	5 6.8%	1 1.4%	3 4.2%	9 12.3%
Glucose, Week 40, Low	0 0%	1 1.4%	0 0%	0 0%	0 0%	0 0%	0 0%
Glucose, Week 52, High	6 8.2%	3 4.2%	7 9.5%	5 6.8%	4 5.5%	3 4.2%	5 6.8%
Haemoglobin, Week 8, High	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.4%
Lymphocytes, Day 1, Low	1 1.4%	3 4.2%	3 4.1%	3 4.1%	3 4.1%	0 0%	1 1.4%
Lymphocytes, Week 4, Low	0 0%	1 1.4%	2 2.7%	3 4.1%	1 1.4%	1 1.4%	1 1.4%
Lymphocytes, Week 12, Low	2 2.7%	0 0%	2 2.7%	2 2.7%	2 2.7%	2 2.8%	1 1.4%
Lymphocytes, Week 28, Low	1 1.4%	0 0%	2 2.7%	2 2.7%	2 2.7%	0 0%	2 2.7%
Lymphocytes, Week 40, Low	2 2.7%	1 1.4%	3 4.1%	4 5.5%	0 0%	1 1.4%	0 0%
Lymphocytes, Week 52, Low	1 1.4%	1 1.4%	1 1.4%	2 2.7%	2 2.7%	3 4.2%	1 1.4%
Platelet count, Day 1, High	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.4%	0 0%
Platelet count, Day 1, Low	0 0%	0 0%	1 1.4%	0 0%	1 1.4%	0 0%	0 0%
Platelet count, Week 4, High	1 1.4%	0 0%	0 0%	0 0%	0 0%	1 1.4%	0 0%
Platelet count, Week 4, Low	1 1.4%	0 0%	2 2.7%	0 0%	0 0%	0 0%	0 0%
Platelet count, Week 12, High	1 1.4%	0 0%	0 0%	1 1.4%	0 0%	2 2.8%	0 0%
Platelet count, Week 12, Low	0 0%	0 0%	0 0%	1 1.4%	0 0%	0 0%	0 0%
Platelet count, Week 28, High	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.4%	0 0%
Platelet count, Week 28, Low	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.4%
Platelet count, Week 40, High	0 0%	0 0%	0 0%	0 0%	1 1.4%	1 1.4%	0 0%
Platelet count, Week 44, High	0 0%	0 0%	1 1.4%	0 0%
Platelet count, Week 52, High	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.4%	0 0%
Potassium, Day 1, High	1 1.4%	3 4.2%	1 1.4%	0 0%	0 0%	0 0%	0 0%
Potassium, Day 1, Low	0 0%	0 0%	0 0%	1 1.4%	0 0%	0 0%	1 1.4%
Potassium, Week 4, High	0 0%	1 1.4%	0 0%	1 1.4%	0 0%	0 0%	2 2.7%
Potassium, Week 4, Low	0 0%	0 0%	0 0%	1 1.4%	0 0%	0 0%	0 0%
Potassium, Week 12, High	3 4.1%	0 0%	1 1.4%	0 0%	0 0%	0 0%	1 1.4%
Potassium, Week 12, Low	0 0%	0 0%	0 0%	1 1.4%	0 0%	0 0%	0 0%
Potassium, Week 28, High	1 1.4%	1 1.4%	0 0%	0 0%	0 0%	0 0%	1 1.4%
Potassium, Week 40, High	0 0%	1 1.4%	0 0%	2 2.7%	0 0%	1 1.4%	0 0%
Potassium, Week 52, High	1 1.4%	0 0%	1 1.4%	0 0%	2 2.7%	1 1.4%	0 0%
Sodium, Week 12, High	1 1.4%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Sodium, Week 40, Low	0 0%	0 0%	0 0%	0 0%	1 1.4%	0 0%	0 0%
Sodium, Week 52, Low	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	2 2.7%
TSH, Day 1, High	2 2.7%	2 2.8%	3 4.1%	3 4.1%	2 2.7%	1 1.4%	1 1.4%
TSH, Week 12, High	1 1.4%	1 1.4%	2 2.7%	1 1.4%	1 1.4%	3 4.2%	0 0%
TSH, Week 24, High	0 0%	2 2.8%	2 2.7%	4 5.5%	2 2.7%	2 2.8%	1 1.4%
TSH, Week 36, High	1 1.4%	2 2.8%	3 4.1%	5 6.8%	3 4.1%	2 2.8%	2 2.7%
TSH, Week 52, High	3 4.1%	2 2.8%	1 1.4%	4 5.5%	2 2.7%	3 4.2%	4 5.5%
Total Bilirubin, Week 24, High	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.4%	0 0%
Total Bilirubin, Week 32, High	1 1.4%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Total Bilirubin, Week 44, High	1 1.4%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Total Neutrophils, Day 1, Low	0 0%	1 1.4%	2 2.7%	0 0%	1 1.4%	0 0%	2 2.7%
Total Neutrophils, Week 4, Low	0 0%	1 1.4%	1 1.4%	0 0%	0 0%	1 1.4%	1 1.4%
Total Neutrophils, Week 12, Low	1 1.4%	2 2.8%	0 0%	0 0%	0 0%	0 0%	0 0%
Total Neutrophils, Week 32, Low	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.4%	0 0%
Total Neutrophils, Week 40, Low	0 0%	0 0%	0 0%	0 0%	1 1.4%	0 0%	0 0%
Total Neutrophils, Week 52, Low	0 0%	0 0%	0 0%	0 0%	1 1.4%	0 0%	0 0%
BUN, Day 1, High	1 1.4%	0 0%	0 0%	0 0%	0 0%	1 1.4%	0 0%
BUN, Week 4, High	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.4%	0 0%
BUN, Week 12, High	0 0%	0 0%	0 0%	1 1.4%	0 0%	2 2.8%	1 1.4%
BUN, Week 16, High	0 0%	0 0%	0 0%	1 1.4%	0 0%	0 0%	0 0%
BUN, Week 28, High	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.4%
BUN, Week 40, High	0 0%	0 0%	0 0%	3 4.1%	0 0%	0 0%	1 1.4%
WBC, DAy 1, Low	0 0%	1 1.4%	1 1.4%	0 0%	0 0%	0 0%	0 0%
WBC, Week 28, Low	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.4%
WBC, Week 52, High	1 1.4%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

17. Secondary Outcome

Title	Number of Participants With Laboratory Data of Clinical Concern for Urine Protein
Description	Urine Samples were collected from Day 1 to Week 28 and Week 52 for analyses. In this dipstick test, the level of protein in urine samples was recorded as negative (Neg), trace (tr), 1+, 2+, and 3+ (the plus sign increases with a higher level of proteins in the urine: 1+=slightly positive, 2+=positive, 3+=high positive). Neg indicated no proteinuria and 3+(high positive) indicated worst proteinuria.
Time Frame	Day 1 to Week 28 and Week 52

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Placebo Control Arm QID	Pazopanib Eye Drops 5 mg/mL TID	Pazopanib Eye Drops 5 mg/mL QID	Pazopanib Eye Drops 10 mg/mL BID	Pazopanib Eye Drops 10 mg/mL TID	Pazopanib Eye Drops 10 mg/mL QID	Ranibizumab Injections Active Open-label Control Arm
Arm/Group Description	Only the study eye (one eye) per participant enrolled in the study received Placebo QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week treatment period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL TID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL twice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL thrice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL four times daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Participants enrolled in this arm received no eye drops. They received a 0.20 mL to 0.23 mL fill of 10 mg/mL Ranibizumab injection once every four weeks throughout the entire 52 weeks of the study.
Measure Participants	73	72	74	73	73	72	73
Week 4	7 9.6%	3 4.2%	5 6.8%	6 8.2%	2 2.7%	1 1.4%	2 2.7%
Week 8	0 0%	0 0%	1 1.4%	0 0%	0 0%	0 0%	1 1.4%
Week 16	1 1.4%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Week 28	7 9.6%	5 6.9%	4 5.4%	8 11%	4 5.5%	2 2.8%	6 8.2%
Week 32	0 0%	1 1.4%	0 0%	0 0%	1 1.4%	0 0%	0 0%
Week 52	2 2.7%	3 4.2%	8 10.8%	10 13.7%	5 6.8%	3 4.2%	3 4.1%

18. Secondary Outcome

Title	Plasma Concentrations of Pazopanib
Description	All participants in the eye drop containing arms had a single blood sample drawn for assessment of pazopanib plasma concentration at the Week 4, Week 24 and Week 24. The sample was drawn without restriction for the time interval between blood draw and the last dose of IP eye drops.
Time Frame	Week 4, Week 24 and Week 52

Outcome Measure Data

Analysis Population Description

Safety Population. Only participants with data available at the indicated time points were analyzed.

Arm/Group Title	Pazopanib Eye Drops 5 mg/mL TID	Pazopanib Eye Drops 5 mg/mL QID	Pazopanib Eye Drops 10 mg/mL BID	Pazopanib Eye Drops 10 mg/mL TID	Pazopanib Eye Drops 10 mg/mL QID
Arm/Group Description	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL TID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL twice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL thrice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.	Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL four times daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.
Measure Participants	72	74	73	73	72
Week 4	80.20	103.38	93.82	114.33	175.89
Week 24	81.94	101.96	104.88	114.58	183.32
Week 52	NA	44.04	60.98	28.77	40.33

Adverse Events

Time Frame	All AEs and SAEs were collected during the treatment period (up to 52 weeks)
Adverse Event Reporting Description	All AEs and SAEs were reported on Safety Population.
Arm/Group Title	Placebo Control Arm QID		Pazopanib Eye Drops 5 mg/mL TID		Pazopanib Eye Drops 5 mg/mL QID		Pazopanib Eye Drops 10 mg/mL BID		Pazopanib Eye Drops 10 mg/mL TID		Pazopanib Eye Drops 10 mg/mL QID		Ranibizumab Injections Active Open-label Control Arm
Arm/Group Description	Only the study eye (one eye) per participant enrolled in the study received Placebo QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week treatment period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.		Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL TID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.		Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 5 mg/mL QID. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.		Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL twice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.		Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL thrice daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.		Only the study eye (one eye) per participant enrolled in the study received pazopanib eye drops 10 mg/mL four times daily. Participants in this treatment arm were educated on the packaging and labeling of the eye drop, required refrigerated storage conditions, and proper dosing method. The study staff witnessed participants self-administering the first dose of the eye drop. Caregiver assistance was permitted. This witnessed dose occurred in the clinic on Day 1 of treatment. Participants continued to administer the eye drop daily for the duration of the 52-week Treatment Period. Ranibizumab IP injection was given whenever re-injection was necessary throughout the study.		Participants enrolled in this arm received no eye drops. They received a 0.20 mL to 0.23 mL fill of 10 mg/mL Ranibizumab injection once every four weeks throughout the entire 52 weeks of the study.
All Cause Mortality
	Placebo Control Arm QID		Pazopanib Eye Drops 5 mg/mL TID		Pazopanib Eye Drops 5 mg/mL QID		Pazopanib Eye Drops 10 mg/mL BID		Pazopanib Eye Drops 10 mg/mL TID		Pazopanib Eye Drops 10 mg/mL QID		Ranibizumab Injections Active Open-label Control Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/73 (2.7%)		1/72 (1.4%)		1/74 (1.4%)		0/73 (0%)		3/73 (4.1%)		0/72 (0%)		1/73 (1.4%)
Serious Adverse Events
	Placebo Control Arm QID		Pazopanib Eye Drops 5 mg/mL TID		Pazopanib Eye Drops 5 mg/mL QID		Pazopanib Eye Drops 10 mg/mL BID		Pazopanib Eye Drops 10 mg/mL TID		Pazopanib Eye Drops 10 mg/mL QID		Ranibizumab Injections Active Open-label Control Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/73 (15.1%)		10/72 (13.9%)		12/74 (16.2%)		11/73 (15.1%)		10/73 (13.7%)		11/72 (15.3%)		6/73 (8.2%)
Blood and lymphatic system disorders
Iron deficiency anaemia	0/73 (0%)		0/72 (0%)		0/74 (0%)		1/73 (1.4%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Cardiac disorders
Angina pectoris	0/73 (0%)		0/72 (0%)		2/74 (2.7%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Atrioventricular block second degree	1/73 (1.4%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Cardiac failure congestive	1/73 (1.4%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Coronary artery disease	0/73 (0%)		0/72 (0%)		1/74 (1.4%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Mitral valve disease	0/73 (0%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		1/72 (1.4%)		0/73 (0%)
Myocardial infarction	0/73 (0%)		0/72 (0%)		1/74 (1.4%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Congenital, familial and genetic disorders
Haemorrhagic arteriovenous malformation	0/73 (0%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		1/72 (1.4%)		0/73 (0%)
Ear and labyrinth disorders
Vertigo	0/73 (0%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		2/72 (2.8%)		0/73 (0%)
Eye disorders
Retinal haemorrhage	0/73 (0%)		1/72 (1.4%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Gastrointestinal disorders
Abdominal pain	1/73 (1.4%)		0/72 (0%)		1/74 (1.4%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		1/73 (1.4%)
Small intestinal obstruction	0/73 (0%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		2/72 (2.8%)		0/73 (0%)
Abdominal hernia	1/73 (1.4%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Colitis	0/73 (0%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		1/72 (1.4%)		0/73 (0%)
Crohn's disease	0/73 (0%)		1/72 (1.4%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Duodenal ulcer	0/73 (0%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Gastric ulcer haemorrhage	0/73 (0%)		0/72 (0%)		0/74 (0%)		1/73 (1.4%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Gastritis	0/73 (0%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		1/73 (1.4%)		0/72 (0%)		0/73 (0%)
Intestinal perforation	0/73 (0%)		1/72 (1.4%)		0/74 (0%)		0/73 (0%)		1/73 (1.4%)		0/72 (0%)		0/73 (0%)
General disorders
Device failure	0/73 (0%)		0/72 (0%)		0/74 (0%)		1/73 (1.4%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Hepatobiliary disorders
Bile duct obstruction	0/73 (0%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		1/72 (1.4%)		0/73 (0%)
Bile duct stone	0/73 (0%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		1/72 (1.4%)		0/73 (0%)
Cholecystitis acute	1/73 (1.4%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Cholelithiasis	0/73 (0%)		0/72 (0%)		0/74 (0%)		1/73 (1.4%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Infections and infestations
Cellulitis	0/73 (0%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		1/73 (1.4%)		0/72 (0%)		0/73 (0%)
Endophthalmitis	0/73 (0%)		0/72 (0%)		0/74 (0%)		1/73 (1.4%)		1/73 (1.4%)		0/72 (0%)		0/73 (0%)
Pneumonia	2/73 (2.7%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Abscess intestinal	0/73 (0%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		1/73 (1.4%)		0/72 (0%)		0/73 (0%)
Erysipelas	0/73 (0%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		1/73 (1.4%)
Gastroenteritis	0/73 (0%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		1/73 (1.4%)		0/72 (0%)		0/73 (0%)
Infection	1/73 (1.4%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Periorbital cellulitis	0/73 (0%)		0/72 (0%)		1/74 (1.4%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Injury, poisoning and procedural complications
Cartilage injury	0/73 (0%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		1/73 (1.4%)
Hip fracture	0/73 (0%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		1/72 (1.4%)		0/73 (0%)
Humerus fracture	0/73 (0%)		1/72 (1.4%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Pelvic fracture	1/73 (1.4%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Post procedural complication	0/73 (0%)		1/72 (1.4%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Post-traumatic neck syndrome	0/73 (0%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		1/73 (1.4%)
Rib fracture	0/73 (0%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		1/73 (1.4%)
Road traffic accident	0/73 (0%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		1/73 (1.4%)		0/72 (0%)		0/73 (0%)
Spinal cord injury	0/73 (0%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		1/72 (1.4%)		0/73 (0%)
Investigations
Prothrombin time prolonged	1/73 (1.4%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Metabolism and nutrition disorders
Fluid overload	1/73 (1.4%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Hypercalcaemia	1/73 (1.4%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Hyperkalaemia	1/73 (1.4%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Hyponatraemia	1/73 (1.4%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/73 (0%)		1/72 (1.4%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Lumbar spinal stenosis	0/73 (0%)		0/72 (0%)		1/74 (1.4%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Musculoskeletal chest pain	0/73 (0%)		0/72 (0%)		0/74 (0%)		1/73 (1.4%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Osteoarthritis	0/73 (0%)		0/72 (0%)		0/74 (0%)		1/73 (1.4%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Pain in extremity	0/73 (0%)		1/72 (1.4%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer	1/73 (1.4%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Colon cancer metastatic	0/73 (0%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		1/73 (1.4%)		0/72 (0%)		0/73 (0%)
Colon neoplasm	0/73 (0%)		0/72 (0%)		0/74 (0%)		1/73 (1.4%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Gastrointestinal cancer metastatic	0/73 (0%)		0/72 (0%)		1/74 (1.4%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Lung cancer metastatic	1/73 (1.4%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Lung neoplasm malignant	1/73 (1.4%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Neoplasm malignant	0/73 (0%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		1/73 (1.4%)		0/72 (0%)		0/73 (0%)
Ovarian cancer	0/73 (0%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		1/72 (1.4%)		0/73 (0%)
Prostate cancer	0/73 (0%)		0/72 (0%)		1/74 (1.4%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Nervous system disorders
Cerebrovascular accident	0/73 (0%)		1/72 (1.4%)		1/74 (1.4%)		0/73 (0%)		1/73 (1.4%)		0/72 (0%)		0/73 (0%)
Syncope	1/73 (1.4%)		1/72 (1.4%)		0/74 (0%)		1/73 (1.4%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Transient ischaemic attack	0/73 (0%)		0/72 (0%)		1/74 (1.4%)		1/73 (1.4%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Ataxia	0/73 (0%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		1/73 (1.4%)		0/72 (0%)		0/73 (0%)
Brain Stem Stroke	0/73 (0%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		1/72 (1.4%)		0/73 (0%)
Cerebral haemorrhage	0/73 (0%)		1/72 (1.4%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Cervical myelopathy	0/73 (0%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		1/72 (1.4%)		0/73 (0%)
Encephalopathy	1/73 (1.4%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Myasthenia gravis	0/73 (0%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		1/73 (1.4%)
Renal and urinary disorders
Hypertensive nephropathy	0/73 (0%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		1/72 (1.4%)		0/73 (0%)
Renal artery stenosis	0/73 (0%)		0/72 (0%)		0/74 (0%)		1/73 (1.4%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Renal cyst haemorrhage	0/73 (0%)		1/72 (1.4%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Renal failure acute	0/73 (0%)		0/72 (0%)		1/74 (1.4%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/73 (0%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		1/73 (1.4%)
Prostatomegaly	0/73 (0%)		0/72 (0%)		1/74 (1.4%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/73 (0%)		0/72 (0%)		1/74 (1.4%)		1/73 (1.4%)		0/73 (0%)		0/72 (0%)		1/73 (1.4%)
Pneumonia aspiration	1/73 (1.4%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Pulmonary embolism	0/73 (0%)		0/72 (0%)		0/74 (0%)		1/73 (1.4%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Vascular disorders
Aortic aneurysm	0/73 (0%)		1/72 (1.4%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Hypertension	1/73 (1.4%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Shock	0/73 (0%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		0/73 (0%)		0/72 (0%)		1/73 (1.4%)
Other (Not Including Serious) Adverse Events
	Placebo Control Arm QID		Pazopanib Eye Drops 5 mg/mL TID		Pazopanib Eye Drops 5 mg/mL QID		Pazopanib Eye Drops 10 mg/mL BID		Pazopanib Eye Drops 10 mg/mL TID		Pazopanib Eye Drops 10 mg/mL QID		Ranibizumab Injections Active Open-label Control Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	52/73 (71.2%)		34/72 (47.2%)		47/74 (63.5%)		44/73 (60.3%)		46/73 (63%)		41/72 (56.9%)		42/73 (57.5%)
Blood and lymphatic system disorders
Anaemia	3/73 (4.1%)		0/72 (0%)		0/74 (0%)		0/73 (0%)		4/73 (5.5%)		2/72 (2.8%)		0/73 (0%)
Eye disorders
Conjunctival haemorrhage	5/73 (6.8%)		2/72 (2.8%)		1/74 (1.4%)		7/73 (9.6%)		6/73 (8.2%)		6/72 (8.3%)		2/73 (2.7%)
Retinal haemorrhage	5/73 (6.8%)		3/72 (4.2%)		3/74 (4.1%)		2/73 (2.7%)		4/73 (5.5%)		3/72 (4.2%)		4/73 (5.5%)
Visual acuity reduced	3/73 (4.1%)		3/72 (4.2%)		2/74 (2.7%)		1/73 (1.4%)		6/73 (8.2%)		3/72 (4.2%)		4/73 (5.5%)
Eye pain	7/73 (9.6%)		1/72 (1.4%)		1/74 (1.4%)		1/73 (1.4%)		4/73 (5.5%)		2/72 (2.8%)		5/73 (6.8%)
Vitreous floaters	3/73 (4.1%)		2/72 (2.8%)		2/74 (2.7%)		3/73 (4.1%)		2/73 (2.7%)		3/72 (4.2%)		4/73 (5.5%)
Vision blurred	4/73 (5.5%)		1/72 (1.4%)		2/74 (2.7%)		2/73 (2.7%)		4/73 (5.5%)		2/72 (2.8%)		2/73 (2.7%)
Blepharitis	2/73 (2.7%)		0/72 (0%)		3/74 (4.1%)		1/73 (1.4%)		3/73 (4.1%)		0/72 (0%)		4/73 (5.5%)
Punctate keratitis	4/73 (5.5%)		1/72 (1.4%)		0/74 (0%)		1/73 (1.4%)		3/73 (4.1%)		3/72 (4.2%)		1/73 (1.4%)
Lacrimation increased	0/73 (0%)		1/72 (1.4%)		1/74 (1.4%)		2/73 (2.7%)		1/73 (1.4%)		5/72 (6.9%)		1/73 (1.4%)
Conjunctivitis	0/73 (0%)		0/72 (0%)		2/74 (2.7%)		0/73 (0%)		1/73 (1.4%)		6/72 (8.3%)		0/73 (0%)
Dry eye	1/73 (1.4%)		1/72 (1.4%)		1/74 (1.4%)		0/73 (0%)		1/73 (1.4%)		4/72 (5.6%)		1/73 (1.4%)
Conjunctival hyperaemia	0/73 (0%)		1/72 (1.4%)		4/74 (5.4%)		1/73 (1.4%)		0/73 (0%)		0/72 (0%)		2/73 (2.7%)
Cataract cortical	1/73 (1.4%)		0/72 (0%)		4/74 (5.4%)		0/73 (0%)		0/73 (0%)		1/72 (1.4%)		1/73 (1.4%)
Gastrointestinal disorders
Diarrhoea	4/73 (5.5%)		3/72 (4.2%)		2/74 (2.7%)		5/73 (6.8%)		2/73 (2.7%)		3/72 (4.2%)		1/73 (1.4%)
Nausea	1/73 (1.4%)		1/72 (1.4%)		0/74 (0%)		3/73 (4.1%)		3/73 (4.1%)		4/72 (5.6%)		3/73 (4.1%)
General disorders
Pain	1/73 (1.4%)		4/72 (5.6%)		2/74 (2.7%)		3/73 (4.1%)		2/73 (2.7%)		3/72 (4.2%)		1/73 (1.4%)
Injection site haemorrhage	1/73 (1.4%)		0/72 (0%)		1/74 (1.4%)		1/73 (1.4%)		2/73 (2.7%)		0/72 (0%)		4/73 (5.5%)
Immune system disorders
Seasonal allergy	3/73 (4.1%)		1/72 (1.4%)		4/74 (5.4%)		2/73 (2.7%)		0/73 (0%)		1/72 (1.4%)		2/73 (2.7%)
Infections and infestations
Nasopharyngitis	11/73 (15.1%)		5/72 (6.9%)		6/74 (8.1%)		17/73 (23.3%)		5/73 (6.8%)		13/72 (18.1%)		5/73 (6.8%)
Urinary tract infection	9/73 (12.3%)		3/72 (4.2%)		1/74 (1.4%)		6/73 (8.2%)		6/73 (8.2%)		4/72 (5.6%)		3/73 (4.1%)
Upper respiratory tract infection	2/73 (2.7%)		1/72 (1.4%)		6/74 (8.1%)		2/73 (2.7%)		4/73 (5.5%)		3/72 (4.2%)		3/73 (4.1%)
Sinusitis	1/73 (1.4%)		1/72 (1.4%)		4/74 (5.4%)		3/73 (4.1%)		1/73 (1.4%)		4/72 (5.6%)		5/73 (6.8%)
Bronchitis	3/73 (4.1%)		1/72 (1.4%)		2/74 (2.7%)		2/73 (2.7%)		4/73 (5.5%)		2/72 (2.8%)		4/73 (5.5%)
Influenza	0/73 (0%)		5/72 (6.9%)		2/74 (2.7%)		3/73 (4.1%)		3/73 (4.1%)		0/72 (0%)		3/73 (4.1%)
Pneumonia	2/73 (2.7%)		0/72 (0%)		4/74 (5.4%)		3/73 (4.1%)		0/73 (0%)		0/72 (0%)		0/73 (0%)
Injury, poisoning and procedural complications
Fall	2/73 (2.7%)		4/72 (5.6%)		2/74 (2.7%)		2/73 (2.7%)		2/73 (2.7%)		1/72 (1.4%)		0/73 (0%)
Musculoskeletal and connective tissue disorders
Back pain	5/73 (6.8%)		2/72 (2.8%)		5/74 (6.8%)		2/73 (2.7%)		4/73 (5.5%)		2/72 (2.8%)		1/73 (1.4%)
Pain in extremity	2/73 (2.7%)		3/72 (4.2%)		4/74 (5.4%)		2/73 (2.7%)		2/73 (2.7%)		3/72 (4.2%)		0/73 (0%)
Arthralgia	2/73 (2.7%)		2/72 (2.8%)		1/74 (1.4%)		2/73 (2.7%)		0/73 (0%)		3/72 (4.2%)		4/73 (5.5%)
Nervous system disorders
Headache	3/73 (4.1%)		2/72 (2.8%)		1/74 (1.4%)		5/73 (6.8%)		5/73 (6.8%)		7/72 (9.7%)		6/73 (8.2%)
Dizziness	0/73 (0%)		1/72 (1.4%)		1/74 (1.4%)		0/73 (0%)		0/73 (0%)		5/72 (6.9%)		3/73 (4.1%)
Respiratory, thoracic and mediastinal disorders
Cough	8/73 (11%)		3/72 (4.2%)		6/74 (8.1%)		4/73 (5.5%)		2/73 (2.7%)		3/72 (4.2%)		3/73 (4.1%)
Skin and subcutaneous tissue disorders
Rash	1/73 (1.4%)		0/72 (0%)		0/74 (0%)		1/73 (1.4%)		4/73 (5.5%)		0/72 (0%)		0/73 (0%)
Vascular disorders
Hypertension	3/73 (4.1%)		4/72 (5.6%)		5/74 (6.8%)		4/73 (5.5%)		6/73 (8.2%)		6/72 (8.3%)		7/73 (9.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.