Trial Outcomes & Findings for Dose Ranging Study of Pazopanib to Treat Neovascular Age-Related Macular Degeneration (NCT NCT01134055)

NCT ID: NCT01134055

Last Updated: 2018-01-08

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 510 participants
• Primary outcome timeframe: Day 1 and 52 weeks
• Results posted on: 2018-01-08

Participant Flow

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.

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.

Participant milestones

Measure	Placebo Control Arm QID 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.	Pazopanib Eye Drops 5 mg/mL TID 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.	Pazopanib Eye Drops 5 mg/mL QID 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.	Pazopanib Eye Drops 10 mg/mL BID 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.	Pazopanib Eye Drops 10 mg/mL TID 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.	Pazopanib Eye Drops 10 mg/mL QID 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.	Ranibizumab Injections Active Open-label Control Arm 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.
Overall Study STARTED	73	72	74	73	73	72	73
Overall Study COMPLETED	65	66	71	67	67	65	62
Overall Study NOT COMPLETED	8	6	3	6	6	7	11

Reasons for withdrawal

Measure	Placebo Control Arm QID 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.	Pazopanib Eye Drops 5 mg/mL TID 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.	Pazopanib Eye Drops 5 mg/mL QID 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.	Pazopanib Eye Drops 10 mg/mL BID 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.	Pazopanib Eye Drops 10 mg/mL TID 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.	Pazopanib Eye Drops 10 mg/mL QID 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.	Ranibizumab Injections Active Open-label Control Arm 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.
Overall Study Adverse Event	5	2	2	2	5	7	2
Overall Study Lost to Follow-up	0	1	0	1	0	0	0
Overall Study Withdrawal by Subject	3	3	1	2	0	0	8
Overall Study Protocol Violation	0	0	0	1	1	0	0
Overall Study Physician Decision	0	0	0	0	0	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Placebo Control Arm QID n=73 Participants 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.	Pazopanib Eye Drops 5 mg/mL TID n=72 Participants 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.	Pazopanib Eye Drops 5 mg/mL QID n=74 Participants 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.	Pazopanib Eye Drops 10 mg/mL BID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL TID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL QID n=72 Participants 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.	Ranibizumab Injections Active Open-label Control Arm n=73 Participants 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 n=510 Participants Total of all reporting groups
Age, Continuous	75.6 Years STANDARD_DEVIATION 9.42 • n=5 Participants	74.4 Years STANDARD_DEVIATION 7.60 • n=7 Participants	75.1 Years STANDARD_DEVIATION 8.19 • n=5 Participants	75.4 Years STANDARD_DEVIATION 8.42 • n=4 Participants	75.6 Years STANDARD_DEVIATION 8.71 • n=21 Participants	76.2 Years STANDARD_DEVIATION 8.00 • n=8 Participants	74.9 Years STANDARD_DEVIATION 7.27 • n=8 Participants	75.3 Years STANDARD_DEVIATION 8.23 • n=24 Participants
Sex: Female, Male Female	39 Participants n=5 Participants	43 Participants n=7 Participants	42 Participants n=5 Participants	45 Participants n=4 Participants	40 Participants n=21 Participants	46 Participants n=8 Participants	41 Participants n=8 Participants	296 Participants n=24 Participants
Sex: Female, Male Male	34 Participants n=5 Participants	29 Participants n=7 Participants	32 Participants n=5 Participants	28 Participants n=4 Participants	33 Participants n=21 Participants	26 Participants n=8 Participants	32 Participants n=8 Participants	214 Participants n=24 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants	6 Participants n=4 Participants	5 Participants n=21 Participants	4 Participants n=8 Participants	6 Participants n=8 Participants	35 Participants n=24 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	1 Participants n=24 Participants
Race (NIH/OMB) White	68 Participants n=5 Participants	67 Participants n=7 Participants	69 Participants n=5 Participants	67 Participants n=4 Participants	68 Participants n=21 Participants	68 Participants n=8 Participants	67 Participants n=8 Participants	474 Participants n=24 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants

PRIMARY outcome

Timeframe: Day 1 and 52 weeks

Population: 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.

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.

Outcome measures

Measure	Placebo Control Arm QID n=73 Participants 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.	Pazopanib Eye Drops 5 mg/mL TID n=72 Participants 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.	Pazopanib Eye Drops 5 mg/mL QID n=74 Participants 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.	Pazopanib Eye Drops 10 mg/mL BID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL TID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL QID n=72 Participants 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.	Ranibizumab Injections Active Open-label Control Arm n=73 Participants 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.
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	0.22 Letters Standard Error 1.006	1.15 Letters Standard Error 1.004	1.81 Letters Standard Error 0.975	0.76 Letters Standard Error 0.995	0.28 Letters Standard Error 0.992	0.62 Letters Standard Error 1.007	1.42 Letters Standard Error 1.020

SECONDARY outcome

Timeframe: Up to 52 weeks

Population: Intent to Treat Population

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.

Outcome measures

Measure	Placebo Control Arm QID n=73 Participants 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.	Pazopanib Eye Drops 5 mg/mL TID n=72 Participants 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.	Pazopanib Eye Drops 5 mg/mL QID n=74 Participants 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.	Pazopanib Eye Drops 10 mg/mL BID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL TID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL QID n=72 Participants 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.	Ranibizumab Injections Active Open-label Control Arm 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.
Percentage of Ranibizumab Re-injections Received Over 28 and 52 Weeks Injection Rate at 28 Weeks	65.04 Percentage of re-injections Standard Error 3.418	55.03 Percentage of re-injections Standard Error 3.441	67.92 Percentage of re-injections Standard Error 3.395	66.11 Percentage of re-injections Standard Error 3.418	61.61 Percentage of re-injections Standard Error 3.418	59.42 Percentage of re-injections Standard Error 3.441	—
Percentage of Ranibizumab Re-injections Received Over 28 and 52 Weeks Overall Injection Rate at 52 weeks	64.24 Percentage of re-injections Standard Error 3.263	55.09 Percentage of re-injections Standard Error 3.286	65.87 Percentage of re-injections Standard Error 3.241	62.50 Percentage of re-injections Standard Error 3.263	64.42 Percentage of re-injections Standard Error 3.263	58.19 Percentage of re-injections Standard Error 3.286	—

SECONDARY outcome

Timeframe: Up to Week 52

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

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.

Outcome measures

Measure	Placebo Control Arm QID n=73 Participants 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.	Pazopanib Eye Drops 5 mg/mL TID n=72 Participants 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.	Pazopanib Eye Drops 5 mg/mL QID n=74 Participants 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.	Pazopanib Eye Drops 10 mg/mL BID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL TID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL QID n=72 Participants 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.	Ranibizumab Injections Active Open-label Control Arm n=73 Participants 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.
Number of Participants With BCVA Over Time Week 12, Fellow Eye · within 5 letters	36 Participants	41 Participants	52 Participants	46 Participants	47 Participants	49 Participants	45 Participants
Number of Participants With BCVA Over Time Week 12, Study Eye · within 5 letters	26 Participants	25 Participants	48 Participants	41 Participants	35 Participants	34 Participants	46 Participants
Number of Participants With BCVA Over Time Week 12, Fellow Eye · within 10 letters	23 Participants	18 Participants	18 Participants	20 Participants	23 Participants	16 Participants	18 Participants
Number of Participants With BCVA Over Time Week 20, Study Eye · more than 15 letters	6 Participants	8 Participants	2 Participants	4 Participants	3 Participants	5 Participants	1 Participants
Number of Participants With BCVA Over Time Week 20, Fellow Eye · more than 15 letters	4 Participants	4 Participants	1 Participants	3 Participants	0 Participants	3 Participants	4 Participants
Number of Participants With BCVA Over Time Week 24, Study Eye · more than 15 letters	7 Participants	8 Participants	2 Participants	3 Participants	3 Participants	6 Participants	1 Participants
Number of Participants With BCVA Over Time Week 24, Study Eye · within 15 letters	14 Participants	8 Participants	12 Participants	9 Participants	11 Participants	11 Participants	6 Participants
Number of Participants With BCVA Over Time Week 24, Fellow Eye · within 10 letters	30 Participants	29 Participants	29 Participants	25 Participants	30 Participants	25 Participants	22 Participants
Number of Participants With BCVA Over Time Week 24, Fellow Eye · within 15 letters	8 Participants	11 Participants	5 Participants	9 Participants	9 Participants	3 Participants	7 Participants
Number of Participants With BCVA Over Time Week 28, Study Eye · within 5 letters	19 Participants	13 Participants	26 Participants	24 Participants	22 Participants	17 Participants	18 Participants
Number of Participants With BCVA Over Time Week 36, Fellow Eye · more than 15 letters	8 Participants	4 Participants	3 Participants	5 Participants	3 Participants	5 Participants	8 Participants
Number of Participants With BCVA Over Time Week 40, Study Eye · within 15 letters	12 Participants	16 Participants	14 Participants	7 Participants	11 Participants	9 Participants	10 Participants
Number of Participants With BCVA Over Time Week 40, Fellow Eye · more than 15 letters	8 Participants	3 Participants	3 Participants	5 Participants	4 Participants	6 Participants	9 Participants
Number of Participants With BCVA Over Time Week 44, Study Eye · within 5 letters	11 Participants	10 Participants	18 Participants	17 Participants	17 Participants	13 Participants	11 Participants
Number of Participants With BCVA Over Time Week 44, Fellow Eye · within 5 letters	15 Participants	16 Participants	22 Participants	20 Participants	21 Participants	25 Participants	19 Participants
Number of Participants With BCVA Over Time Week 44, Fellow Eye · within 10 letters	35 Participants	36 Participants	36 Participants	32 Participants	36 Participants	30 Participants	29 Participants
Number of Participants With BCVA Over Time Week 48, Study Eye · within 5 letters	10 Participants	9 Participants	14 Participants	16 Participants	15 Participants	13 Participants	11 Participants
Number of Participants With BCVA Over Time Week 8, Fellow Eye · within 5 letters	42 Participants	48 Participants	60 Participants	52 Participants	52 Participants	55 Participants	51 Participants
Number of Participants With BCVA Over Time Week 8, Fellow Eye · within 10 letters	19 Participants	17 Participants	10 Participants	20 Participants	18 Participants	11 Participants	15 Participants
Number of Participants With BCVA Over Time Week 8, Fellow Eye · within 15 letters	9 Participants	5 Participants	2 Participants	1 Participants	1 Participants	3 Participants	5 Participants
Number of Participants With BCVA Over Time Week 28, Study Eye · within 15 letters	14 Participants	9 Participants	14 Participants	9 Participants	11 Participants	10 Participants	10 Participants
Number of Participants With BCVA Over Time Week 52, Study Eye · within 5 letters	11 Participants	8 Participants	12 Participants	15 Participants	13 Participants	13 Participants	10 Participants
Number of Participants With BCVA Over Time Week 52, Study Eye · within 10 letters	32 Participants	31 Participants	38 Participants	31 Participants	37 Participants	31 Participants	35 Participants
Number of Participants With BCVA Over Time Week 52, Study Eye · within 15 letters	11 Participants	19 Participants	15 Participants	14 Participants	10 Participants	8 Participants	15 Participants
Number of Participants With BCVA Over Time Week 16, Fellow Eye · within 15 letters	9 Participants	8 Participants	3 Participants	4 Participants	4 Participants	3 Participants	7 Participants
Number of Participants With BCVA Over Time Week 12, Study Eye · within 10 letters	27 Participants	30 Participants	17 Participants	23 Participants	25 Participants	24 Participants	22 Participants
Number of Participants With BCVA Over Time Week 12, Study Eye · within 15 letters	13 Participants	8 Participants	8 Participants	4 Participants	10 Participants	9 Participants	2 Participants
Number of Participants With BCVA Over Time Week 12, Study Eye · more than 15 letters	5 Participants	5 Participants	1 Participants	4 Participants	2 Participants	2 Participants	0 Participants
Number of Participants With BCVA Over Time Week 12, Fellow Eye · within 15 letters	9 Participants	8 Participants	2 Participants	4 Participants	2 Participants	1 Participants	6 Participants
Number of Participants With BCVA Over Time Week 12, Fellow Eye · more than 15 letters	4 Participants	1 Participants	1 Participants	1 Participants	0 Participants	3 Participants	1 Participants
Number of Participants With BCVA Over Time Week 16, Study Eye · within 5 letters	24 Participants	20 Participants	41 Participants	36 Participants	26 Participants	26 Participants	35 Participants
Number of Participants With BCVA Over Time Week 16, Study Eye · within 10 letters	28 Participants	37 Participants	22 Participants	25 Participants	29 Participants	29 Participants	30 Participants
Number of Participants With BCVA Over Time Week 16, Study Eye · within 15 letters	10 Participants	4 Participants	9 Participants	4 Participants	13 Participants	11 Participants	3 Participants
Number of Participants With BCVA Over Time Week 16, Study Eye · more than 15 letters	9 Participants	7 Participants	1 Participants	5 Participants	3 Participants	3 Participants	0 Participants
Number of Participants With BCVA Over Time Week 16, Fellow Eye · within 5 letters	35 Participants	32 Participants	47 Participants	40 Participants	42 Participants	43 Participants	39 Participants
Number of Participants With BCVA Over Time Week 16, Fellow Eye · within 10 letters	24 Participants	24 Participants	21 Participants	25 Participants	25 Participants	20 Participants	19 Participants
Number of Participants With BCVA Over Time Week 8, Fellow Eye · more than 15 letters	2 Participants	0 Participants	1 Participants	0 Participants	0 Participants	2 Participants	1 Participants
Number of Participants With BCVA Over Time Week 16, Fellow Eye · more than 15 letters	4 Participants	4 Participants	1 Participants	1 Participants	0 Participants	3 Participants	3 Participants
Number of Participants With BCVA Over Time Week 24, Study Eye · within 5 letters	19 Participants	16 Participants	28 Participants	26 Participants	23 Participants	20 Participants	25 Participants
Number of Participants With BCVA Over Time Week 24, Study Eye · within 10 letters	29 Participants	36 Participants	30 Participants	31 Participants	34 Participants	32 Participants	34 Participants
Number of Participants With BCVA Over Time Week 28, Fellow Eye · within 15 letters	7 Participants	10 Participants	7 Participants	9 Participants	7 Participants	2 Participants	6 Participants
Number of Participants With BCVA Over Time Week 28, Fellow Eye · more than 15 letters	7 Participants	4 Participants	2 Participants	5 Participants	1 Participants	5 Participants	7 Participants
Number of Participants With BCVA Over Time Week 32, Study Eye · within 5 letters	17 Participants	11 Participants	23 Participants	23 Participants	20 Participants	14 Participants	12 Participants
Number of Participants With BCVA Over Time Week 44, Study Eye · within 10 letters	36 Participants	33 Participants	35 Participants	32 Participants	33 Participants	32 Participants	38 Participants
Number of Participants With BCVA Over Time Week 20, Study Eye · within 5 letters	21 Participants	19 Participants	32 Participants	32 Participants	26 Participants	21 Participants	30 Participants
Number of Participants With BCVA Over Time Week 32, Study Eye · within 10 letters	32 Participants	37 Participants	33 Participants	32 Participants	32 Participants	35 Participants	38 Participants
Number of Participants With BCVA Over Time Week 20, Study Eye · within 10 letters	32 Participants	36 Participants	25 Participants	26 Participants	30 Participants	32 Participants	31 Participants
Number of Participants With BCVA Over Time Week 52, Study Eye · more than 15 letters	10 Participants	8 Participants	6 Participants	7 Participants	7 Participants	12 Participants	2 Participants
Number of Participants With BCVA Over Time Week 20, Study Eye · within 15 letters	10 Participants	5 Participants	12 Participants	8 Participants	12 Participants	11 Participants	5 Participants
Number of Participants With BCVA Over Time Week 20, Fellow Eye · within 5 letters	28 Participants	28 Participants	41 Participants	34 Participants	32 Participants	40 Participants	35 Participants
Number of Participants With BCVA Over Time Week 20, Fellow Eye · within 10 letters	28 Participants	27 Participants	25 Participants	28 Participants	33 Participants	23 Participants	20 Participants
Number of Participants With BCVA Over Time Week 20, Fellow Eye · within 15 letters	10 Participants	9 Participants	3 Participants	4 Participants	6 Participants	3 Participants	8 Participants
Number of Participants With BCVA Over Time Week 32, Study Eye · within 15 letters	14 Participants	11 Participants	11 Participants	10 Participants	12 Participants	9 Participants	10 Participants
Number of Participants With BCVA Over Time Week 32, Study Eye · more than 15 letters	4 Participants	9 Participants	3 Participants	4 Participants	4 Participants	8 Participants	3 Participants
Number of Participants With BCVA Over Time Week 32, Fellow Eye · within 5 letters	23 Participants	23 Participants	30 Participants	24 Participants	27 Participants	30 Participants	24 Participants
Number of Participants With BCVA Over Time Week 32, Fellow Eye · within 10 letters	31 Participants	31 Participants	31 Participants	30 Participants	34 Participants	26 Participants	25 Participants
Number of Participants With BCVA Over Time Week 32, Fellow Eye · within 15 letters	8 Participants	10 Participants	5 Participants	8 Participants	4 Participants	5 Participants	6 Participants
Number of Participants With BCVA Over Time Week 32, Fellow Eye · more than 15 letters	6 Participants	4 Participants	3 Participants	7 Participants	3 Participants	5 Participants	8 Participants
Number of Participants With BCVA Over Time Week 36, Study Eye · within 5 letters	16 Participants	10 Participants	22 Participants	20 Participants	19 Participants	13 Participants	12 Participants
Number of Participants With BCVA Over Time Week 52, Fellow Eye · within 5 letters	13 Participants	14 Participants	20 Participants	19 Participants	18 Participants	21 Participants	16 Participants
Number of Participants With BCVA Over Time Week 36, Study Eye · within 10 letters	31 Participants	36 Participants	34 Participants	34 Participants	32 Participants	35 Participants	41 Participants
Number of Participants With BCVA Over Time Week 36, Study Eye · within 15 letters	14 Participants	11 Participants	13 Participants	7 Participants	15 Participants	9 Participants	8 Participants
Number of Participants With BCVA Over Time Week 36, Study Eye · more than 15 letters	4 Participants	9 Participants	2 Participants	7 Participants	3 Participants	10 Participants	2 Participants
Number of Participants With BCVA Over Time Week 36, Fellow Eye · within 5 letters	22 Participants	19 Participants	29 Participants	21 Participants	25 Participants	26 Participants	21 Participants
Number of Participants With BCVA Over Time Week 36, Fellow Eye · within 10 letters	31 Participants	31 Participants	32 Participants	34 Participants	38 Participants	32 Participants	27 Participants
Number of Participants With BCVA Over Time Week 36, Fellow Eye · within 15 letters	6 Participants	12 Participants	6 Participants	8 Participants	3 Participants	4 Participants	7 Participants
Number of Participants With BCVA Over Time Week 40, Study Eye · more than 15 letters	8 Participants	9 Participants	2 Participants	7 Participants	5 Participants	11 Participants	2 Participants
Number of Participants With BCVA Over Time Week 40, Study Eye · within 5 letters	14 Participants	11 Participants	19 Participants	20 Participants	18 Participants	13 Participants	12 Participants
Number of Participants With BCVA Over Time Week 40, Study Eye · within 10 letters	33 Participants	32 Participants	35 Participants	34 Participants	34 Participants	34 Participants	38 Participants
Number of Participants With BCVA Over Time Week 44, Study Eye · within 15 letters	10 Participants	16 Participants	14 Participants	12 Participants	12 Participants	9 Participants	12 Participants
Number of Participants With BCVA Over Time Week 40, Fellow Eye · within 5 letters	20 Participants	16 Participants	23 Participants	21 Participants	23 Participants	25 Participants	21 Participants
Number of Participants With BCVA Over Time Week 40, Fellow Eye · within 10 letters	31 Participants	36 Participants	37 Participants	35 Participants	35 Participants	33 Participants	28 Participants
Number of Participants With BCVA Over Time Week 40, Fellow Eye · within 15 letters	9 Participants	13 Participants	6 Participants	7 Participants	5 Participants	3 Participants	5 Participants
Number of Participants With BCVA Over Time Week 24, Fellow Eye · within 5 letters	27 Participants	24 Participants	36 Participants	32 Participants	32 Participants	36 Participants	33 Participants
Number of Participants With BCVA Over Time Week 24, Fellow Eye · more than 15 letters	5 Participants	4 Participants	1 Participants	3 Participants	0 Participants	5 Participants	4 Participants
Number of Participants With BCVA Over Time Week 28, Study Eye · within 10 letters	30 Participants	37 Participants	29 Participants	33 Participants	32 Participants	33 Participants	35 Participants
Number of Participants With BCVA Over Time Week 28, Study Eye · more than 15 letters	5 Participants	9 Participants	2 Participants	3 Participants	5 Participants	8 Participants	3 Participants
Number of Participants With BCVA Over Time Week 28, Fellow Eye · within 5 letters	26 Participants	24 Participants	34 Participants	27 Participants	29 Participants	34 Participants	31 Participants
Number of Participants With BCVA Over Time Week 28, Fellow Eye · within 10 letters	29 Participants	30 Participants	27 Participants	27 Participants	33 Participants	27 Participants	22 Participants
Number of Participants With BCVA Over Time Week 52, Fellow Eye · within 10 letters	35 Participants	35 Participants	39 Participants	31 Participants	38 Participants	33 Participants	28 Participants
Number of Participants With BCVA Over Time Week 44, Study Eye · more than 15 letters	9 Participants	9 Participants	3 Participants	6 Participants	5 Participants	11 Participants	1 Participants
Number of Participants With BCVA Over Time Week 52, Fellow Eye · within 15 letters	8 Participants	11 Participants	5 Participants	9 Participants	9 Participants	5 Participants	10 Participants
Number of Participants With BCVA Over Time Week 52, Fellow Eye · more than 15 letters	8 Participants	6 Participants	6 Participants	8 Participants	2 Participants	5 Participants	7 Participants
Number of Participants With BCVA Over Time Week 44, Fellow Eye · within 15 letters	8 Participants	12 Participants	7 Participants	9 Participants	6 Participants	4 Participants	7 Participants
Number of Participants With BCVA Over Time Week 44, Fellow Eye · more than 15 letters	9 Participants	4 Participants	4 Participants	6 Participants	4 Participants	6 Participants	8 Participants
Number of Participants With BCVA Over Time Week 48, Study Eye · within 10 letters	36 Participants	32 Participants	37 Participants	31 Participants	36 Participants	32 Participants	36 Participants
Number of Participants With BCVA Over Time Week 48, Study Eye · within 15 letters	9 Participants	18 Participants	16 Participants	13 Participants	12 Participants	11 Participants	13 Participants
Number of Participants With BCVA Over Time Week 48, Study Eye · more than 15 letters	9 Participants	8 Participants	4 Participants	7 Participants	5 Participants	10 Participants	2 Participants
Number of Participants With BCVA Over Time Week 48, Fellow Eye · within 5 letters	14 Participants	14 Participants	20 Participants	18 Participants	21 Participants	24 Participants	17 Participants
Number of Participants With BCVA Over Time Week 48, Fellow Eye · within 10 letters	35 Participants	36 Participants	40 Participants	33 Participants	38 Participants	31 Participants	26 Participants
Number of Participants With BCVA Over Time Week 48, Fellow Eye · within 15 letters	8 Participants	12 Participants	5 Participants	8 Participants	7 Participants	5 Participants	10 Participants
Number of Participants With BCVA Over Time Week 48, Fellow Eye · more than 15 letters	8 Participants	5 Participants	5 Participants	7 Participants	2 Participants	6 Participants	9 Participants
Number of Participants With BCVA Over Time Week 4, Study Eye · within 5 letters	49 Participants	49 Participants	57 Participants	57 Participants	58 Participants	57 Participants	62 Participants
Number of Participants With BCVA Over Time Week 4, Study Eye · within 10 letters	11 Participants	15 Participants	12 Participants	13 Participants	12 Participants	11 Participants	8 Participants
Number of Participants With BCVA Over Time Week 4, Study Eye · within 15 letters	6 Participants	5 Participants	5 Participants	1 Participants	3 Participants	2 Participants	3 Participants
Number of Participants With BCVA Over Time Week 4, Study Eye · more than 15 letters	5 Participants	2 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With BCVA Over Time Week 4, Fellow Eye · within 5 letters	53 Participants	57 Participants	65 Participants	59 Participants	61 Participants	60 Participants	60 Participants
Number of Participants With BCVA Over Time Week 4, Fellow Eye · within 10 letters	16 Participants	12 Participants	6 Participants	12 Participants	11 Participants	7 Participants	11 Participants
Number of Participants With BCVA Over Time Week 4, Fellow Eye · within 15 letters	2 Participants	2 Participants	2 Participants	1 Participants	1 Participants	3 Participants	2 Participants
Number of Participants With BCVA Over Time Week 4, Fellow Eye · more than 15 letters	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With BCVA Over Time Week 8, Study Eye · within 5 letters	34 Participants	36 Participants	51 Participants	51 Participants	44 Participants	47 Participants	54 Participants
Number of Participants With BCVA Over Time Week 8, Study Eye · within 10 letters	21 Participants	23 Participants	18 Participants	18 Participants	20 Participants	16 Participants	14 Participants
Number of Participants With BCVA Over Time Week 8, Study Eye · within 15 letters	11 Participants	7 Participants	5 Participants	1 Participants	6 Participants	7 Participants	4 Participants
Number of Participants With BCVA Over Time Week 8, Study Eye · more than 15 letters	5 Participants	4 Participants	0 Participants	3 Participants	1 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Week 52

Population: Intent to Treat Population

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.

Outcome measures

Measure	Placebo Control Arm QID n=73 Participants 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.	Pazopanib Eye Drops 5 mg/mL TID n=72 Participants 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.	Pazopanib Eye Drops 5 mg/mL QID n=74 Participants 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.	Pazopanib Eye Drops 10 mg/mL BID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL TID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL QID n=72 Participants 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.	Ranibizumab Injections Active Open-label Control Arm n=73 Participants 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.
Number of Participants Analyzed for Visual Acuity (VA) Response Over Time	25 Participants	19 Participants	20 Participants	18 Participants	21 Participants	23 Participants	15 Participants

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: Intent to Treat Population

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.

Outcome measures

Measure	Placebo Control Arm QID n=73 Participants 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.	Pazopanib Eye Drops 5 mg/mL TID n=72 Participants 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.	Pazopanib Eye Drops 5 mg/mL QID n=74 Participants 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.	Pazopanib Eye Drops 10 mg/mL BID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL TID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL QID n=72 Participants 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.	Ranibizumab Injections Active Open-label Control Arm n=73 Participants 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.
Change From Baseline in Center Point Thickness (CPT) Over Time Subgroup-Genotype, Week 28, CC	10.0 Microns Standard Deviation 55.29	12.3 Microns Standard Deviation 48.05	3.4 Microns Standard Deviation 56.23	-27.6 Microns Standard Deviation 136.79	16.6 Microns Standard Deviation 75.36	9.7 Microns Standard Deviation 76.41	-10.4 Microns Standard Deviation 79.28
Change From Baseline in Center Point Thickness (CPT) Over Time Subgroup-Genotype, Week 28, CT	9.6 Microns Standard Deviation 77.04	11.1 Microns Standard Deviation 62.94	9.4 Microns Standard Deviation 84.10	-8.9 Microns Standard Deviation 54.05	-8.4 Microns Standard Deviation 87.97	4.2 Microns Standard Deviation 72.25	-18.1 Microns Standard Deviation 101.47
Change From Baseline in Center Point Thickness (CPT) Over Time Subgroup-Genotype, Week 52, CC	12.7 Microns Standard Deviation 76.07	6.9 Microns Standard Deviation 63.99	3.6 Microns Standard Deviation 95.68	-37.3 Microns Standard Deviation 118.33	31.4 Microns Standard Deviation 56.63	7.4 Microns Standard Deviation 93.46	-40.8 Microns Standard Deviation 72.12
Change From Baseline in Center Point Thickness (CPT) Over Time Subgroup-Genotype, Week 52, CT	-2.9 Microns Standard Deviation 48.00	5.5 Microns Standard Deviation 73.67	-10.5 Microns Standard Deviation 65.41	-9.7 Microns Standard Deviation 61.55	-12.3 Microns Standard Deviation 101.63	-7.2 Microns Standard Deviation 89.75	-14.2 Microns Standard Deviation 108.24
Change From Baseline in Center Point Thickness (CPT) Over Time Subgroup-Pre-amendment 3, Week 28	20.9 Microns Standard Deviation 104.87	30.8 Microns Standard Deviation 75.58	-15.9 Microns Standard Deviation 64.65	-44.4 Microns Standard Deviation 114.54	27.8 Microns Standard Deviation 113.06	-28.5 Microns Standard Deviation 101.42	-16.6 Microns Standard Deviation 89.64
Change From Baseline in Center Point Thickness (CPT) Over Time Subgroup-Post-amendment 3, Week 28	9.9 Microns Standard Deviation 72.13	11.0 Microns Standard Deviation 53.06	8.5 Microns Standard Deviation 65.28	-8.6 Microns Standard Deviation 92.03	-7.7 Microns Standard Deviation 66.09	14.1 Microns Standard Deviation 65.43	-15.0 Microns Standard Deviation 87.50
Change From Baseline in Center Point Thickness (CPT) Over Time Subgroup-Pre-amendment 3, Week 52	-24.1 Microns Standard Deviation 66.83	13.8 Microns Standard Deviation 120.91	-57.8 Microns Standard Deviation 85.39	-50.3 Microns Standard Deviation 63.87	-8.2 Microns Standard Deviation 56.80	-9.0 Microns Standard Deviation 142.59	-29.0 Microns Standard Deviation 91.44
Change From Baseline in Center Point Thickness (CPT) Over Time Subgroup-Post-amendment 3, Week 52	0.1 Microns Standard Deviation 64.33	9.6 Microns Standard Deviation 61.19	2.2 Microns Standard Deviation 74.83	-13.7 Microns Standard Deviation 97.67	3.2 Microns Standard Deviation 86.08	-3.0 Microns Standard Deviation 67.15	-23.5 Microns Standard Deviation 90.13

SECONDARY outcome

Timeframe: Up to Week 52

Population: Intent to Treat Population

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.

Outcome measures

Measure	Placebo Control Arm QID n=73 Participants 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.	Pazopanib Eye Drops 5 mg/mL TID n=72 Participants 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.	Pazopanib Eye Drops 5 mg/mL QID n=74 Participants 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.	Pazopanib Eye Drops 10 mg/mL BID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL TID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL QID n=72 Participants 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.	Ranibizumab Injections Active Open-label Control Arm 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.
Number of Participants That Met Criteria for Re-injection Week 52	36 Participants	28 Participants	43 Participants	37 Participants	45 Participants	36 Participants	—
Number of Participants That Met Criteria for Re-injection Week 4	49 Participants	33 Participants	54 Participants	48 Participants	45 Participants	44 Participants	—
Number of Participants That Met Criteria for Re-injection Week 12	45 Participants	40 Participants	49 Participants	47 Participants	46 Participants	42 Participants	—
Number of Participants That Met Criteria for Re-injection Week 16	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—
Number of Participants That Met Criteria for Re-injection Week 20	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	—
Number of Participants That Met Criteria for Re-injection Week 28	38 Participants	41 Participants	45 Participants	47 Participants	39 Participants	36 Participants	—
Number of Participants That Met Criteria for Re-injection Week 32	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	—
Number of Participants That Met Criteria for Re-injection Week 44	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—

SECONDARY outcome

Timeframe: Day 1, Week 28 and Week 52

Population: Intent to Treat Population

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.

Outcome measures

Measure	Placebo Control Arm QID n=73 Participants 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.	Pazopanib Eye Drops 5 mg/mL TID n=72 Participants 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.	Pazopanib Eye Drops 5 mg/mL QID n=74 Participants 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.	Pazopanib Eye Drops 10 mg/mL BID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL TID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL QID n=72 Participants 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.	Ranibizumab Injections Active Open-label Control Arm n=73 Participants 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.
Change From Baseline in the Area of Choroidal Neovascularisation (CNV) Week 28	0.10 Millimeter (mm)^2 Standard Error 0.113	0.16 Millimeter (mm)^2 Standard Error 0.114	0.09 Millimeter (mm)^2 Standard Error 0.111	0.06 Millimeter (mm)^2 Standard Error 0.114	-0.05 Millimeter (mm)^2 Standard Error 0.112	0.13 Millimeter (mm)^2 Standard Error 0.114	-0.08 Millimeter (mm)^2 Standard Error 0.118
Change From Baseline in the Area of Choroidal Neovascularisation (CNV) Week 52	0.10 Millimeter (mm)^2 Standard Error 0.134	0.13 Millimeter (mm)^2 Standard Error 0.133	0.08 Millimeter (mm)^2 Standard Error 0.129	-0.16 Millimeter (mm)^2 Standard Error 0.134	-0.10 Millimeter (mm)^2 Standard Error 0.132	0.13 Millimeter (mm)^2 Standard Error 0.134	-0.08 Millimeter (mm)^2 Standard Error 0.137

SECONDARY outcome

Timeframe: Day 1, Week 28 and Week 52

Population: Intent to Treat Population

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.

Outcome measures

Measure	Placebo Control Arm QID n=73 Participants 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.	Pazopanib Eye Drops 5 mg/mL TID n=72 Participants 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.	Pazopanib Eye Drops 5 mg/mL QID n=74 Participants 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.	Pazopanib Eye Drops 10 mg/mL BID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL TID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL QID n=72 Participants 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.	Ranibizumab Injections Active Open-label Control Arm n=73 Participants 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.
Change From Baseline in the Area of the CNV Lesion Complex (i.e. CNV, Blood, PED, and Fibrosis) Week 28	0.18 mm^2 Standard Error 0.131	0.32 mm^2 Standard Error 0.132	0.23 mm^2 Standard Error 0.129	0.12 mm^2 Standard Error 0.132	0.00 mm^2 Standard Error 0.130	0.13 mm^2 Standard Error 0.132	-0.13 mm^2 Standard Error 0.137
Change From Baseline in the Area of the CNV Lesion Complex (i.e. CNV, Blood, PED, and Fibrosis) Week 52	0.40 mm^2 Standard Error 0.152	0.51 mm^2 Standard Error 0.151	0.09 mm^2 Standard Error 0.146	0.01 mm^2 Standard Error 0.151	-0.05 mm^2 Standard Error 0.150	0.20 mm^2 Standard Error 0.152	-0.11 mm^2 Standard Error 0.155

SECONDARY outcome

Timeframe: Day 1, Week 28 and Week 52

Population: Intent to Treat Population

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.

Outcome measures

Measure	Placebo Control Arm QID n=73 Participants 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.	Pazopanib Eye Drops 5 mg/mL TID n=72 Participants 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.	Pazopanib Eye Drops 5 mg/mL QID n=74 Participants 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.	Pazopanib Eye Drops 10 mg/mL BID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL TID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL QID n=72 Participants 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.	Ranibizumab Injections Active Open-label Control Arm n=73 Participants 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.
Change From Baseline in the Area of Fluorescein Leakage Week 28	-0.33 mm^2 Standard Error 0.150	-0.27 mm^2 Standard Error 0.151	-0.32 mm^2 Standard Error 0.148	-0.40 mm^2 Standard Error 0.151	-0.61 mm^2 Standard Error 0.149	-0.33 mm^2 Standard Error 0.151	-0.60 mm^2 Standard Error 0.156
Change From Baseline in the Area of Fluorescein Leakage Week 52	-0.40 mm^2 Standard Error 0.177	-0.45 mm^2 Standard Error 0.176	-0.19 mm^2 Standard Error 0.171	-0.77 mm^2 Standard Error 0.177	-0.57 mm^2 Standard Error 0.175	-0.37 mm^2 Standard Error 0.178	-0.66 mm^2 Standard Error 0.181

SECONDARY outcome

Timeframe: Day 1, Week 28 and Week 52

Population: Intent to Treat Population

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.

Outcome measures

Measure	Placebo Control Arm QID n=73 Participants 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.	Pazopanib Eye Drops 5 mg/mL TID n=72 Participants 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.	Pazopanib Eye Drops 5 mg/mL QID n=74 Participants 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.	Pazopanib Eye Drops 10 mg/mL BID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL TID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL QID n=72 Participants 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.	Ranibizumab Injections Active Open-label Control Arm n=73 Participants 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.
Change in Area of Serous Sensory Retinal Detachment (SSRD) Week 28	-0.30 mm^2 Standard Error 0.259	-0.28 mm^2 Standard Error 0.264	-0.14 mm^2 Standard Error 0.255	-0.55 mm^2 Standard Error 0.261	-0.64 mm^2 Standard Error 0.261	-0.46 mm^2 Standard Error 0.264	-0.95 mm^2 Standard Error 0.273
Change in Area of Serous Sensory Retinal Detachment (SSRD) Week 52	-0.52 mm^2 Standard Error 0.317	-0.76 mm^2 Standard Error 0.315	-0.79 mm^2 Standard Error 0.300	-1.24 mm^2 Standard Error 0.312	-1.17 mm^2 Standard Error 0.321	-0.83 mm^2 Standard Error 0.321	-1.02 mm^2 Standard Error 0.322

SECONDARY outcome

Timeframe: Up to 52 Weeks

Population: Safety Population

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.

Outcome measures

Measure	Placebo Control Arm QID n=73 Participants 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.	Pazopanib Eye Drops 5 mg/mL TID n=72 Participants 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.	Pazopanib Eye Drops 5 mg/mL QID n=74 Participants 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.	Pazopanib Eye Drops 10 mg/mL BID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL TID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL QID n=72 Participants 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.	Ranibizumab Injections Active Open-label Control Arm n=73 Participants 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.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Adverse Events (AEs)	11 Participants	10 Participants	12 Participants	11 Participants	10 Participants	11 Participants	6 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Serious Adverse Events (SAEs)	52 Participants	34 Participants	47 Participants	44 Participants	46 Participants	41 Participants	42 Participants

SECONDARY outcome

Timeframe: Up to Week 52

Population: Safety population

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.

Outcome measures

Measure	Placebo Control Arm QID n=73 Participants 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.	Pazopanib Eye Drops 5 mg/mL TID n=72 Participants 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.	Pazopanib Eye Drops 5 mg/mL QID n=74 Participants 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.	Pazopanib Eye Drops 10 mg/mL BID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL TID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL QID n=72 Participants 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.	Ranibizumab Injections Active Open-label Control Arm n=73 Participants 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.
Summary of Potentially Clinically Important Findings for Ophthalmic Examinations 2-step worsening of Conjunctival injection, FE	1 Participants	1 Participants	1 Participants	1 Participants	1 Participants	3 Participants	1 Participants
Summary of Potentially Clinically Important Findings for Ophthalmic Examinations Abnormal postbaseline finding of active opacity,FE	2 Participants	0 Participants	3 Participants	0 Participants	2 Participants	0 Participants	0 Participants
Summary of Potentially Clinically Important Findings for Ophthalmic Examinations Afferent papillary defect present, SE	4 Participants	2 Participants	4 Participants	2 Participants	1 Participants	2 Participants	3 Participants
Summary of Potentially Clinically Important Findings for Ophthalmic Examinations Afferent papillary defect present, FE	4 Participants	1 Participants	5 Participants	2 Participants	3 Participants	2 Participants	3 Participants
Summary of Potentially Clinically Important Findings for Ophthalmic Examinations Confrontation visual field abnormal, SE	2 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Summary of Potentially Clinically Important Findings for Ophthalmic Examinations Confrontation visual field abnormal, FE	2 Participants	0 Participants	2 Participants	1 Participants	2 Participants	0 Participants	2 Participants
Summary of Potentially Clinically Important Findings for Ophthalmic Examinations Ptosis present, SE	2 Participants	1 Participants	1 Participants	0 Participants	8 Participants	2 Participants	2 Participants
Summary of Potentially Clinically Important Findings for Ophthalmic Examinations Ptosis present, FE	1 Participants	3 Participants	1 Participants	1 Participants	9 Participants	2 Participants	3 Participants
Summary of Potentially Clinically Important Findings for Ophthalmic Examinations 2-step worsening of Meibomian gland dysfunction,SE	0 Participants	0 Participants	2 Participants	0 Participants	2 Participants	0 Participants	0 Participants
Summary of Potentially Clinically Important Findings for Ophthalmic Examinations 2-step worsening of Chemosis, SE	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants
Summary of Potentially Clinically Important Findings for Ophthalmic Examinations 2-step worsening of Chemosis, FE	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants
Summary of Potentially Clinically Important Findings for Ophthalmic Examinations 2-step worsening of punctate keratopathy, FE	0 Participants	1 Participants	2 Participants	0 Participants	1 Participants	0 Participants	2 Participants
Summary of Potentially Clinically Important Findings for Ophthalmic Examinations 2-step worsening of epithelial edema, SE	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Potentially Clinically Important Findings for Ophthalmic Examinations 2-step worsening of epithelial edema, FE	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Potentially Clinically Important Findings for Ophthalmic Examinations Grade 1+ of Anterior chamber cell, SE	0 Participants	1 Participants	0 Participants	1 Participants	1 Participants	0 Participants	1 Participants
Summary of Potentially Clinically Important Findings for Ophthalmic Examinations Grade 1+ of Anterior chamber cell, FE	1 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants
Summary of Potentially Clinically Important Findings for Ophthalmic Examinations Grade 2+ of Anterior chamber flare, FE	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Summary of Potentially Clinically Important Findings for Ophthalmic Examinations 2+ increases in Any Lens Opacity, FE	3 Participants	1 Participants	4 Participants	4 Participants	4 Participants	4 Participants	6 Participants
Summary of Potentially Clinically Important Findings for Ophthalmic Examinations 2-step worsening of punctate keratopathy, SE	0 Participants	0 Participants	1 Participants	0 Participants	2 Participants	4 Participants	0 Participants
Summary of Potentially Clinically Important Findings for Ophthalmic Examinations Abnormal postbaseline finding of active opacity,SE	1 Participants	0 Participants	3 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Summary of Potentially Clinically Important Findings for Ophthalmic Examinations Eye motility abnormal, SE	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants
Summary of Potentially Clinically Important Findings for Ophthalmic Examinations Eye motility abnormal, FE	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Summary of Potentially Clinically Important Findings for Ophthalmic Examinations 2-step worsening of Meibomian gland dysfunction,FE	0 Participants	0 Participants	4 Participants	0 Participants	2 Participants	0 Participants	0 Participants
Summary of Potentially Clinically Important Findings for Ophthalmic Examinations 2-step worsening of Conjunctival injection, SE	2 Participants	0 Participants	1 Participants	0 Participants	1 Participants	5 Participants	0 Participants
Summary of Potentially Clinically Important Findings for Ophthalmic Examinations Abnormal post-baseline finding of active edema, SE	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Potentially Clinically Important Findings for Ophthalmic Examinations Abnormal post-baseline finding of active edema, FE	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Summary of Potentially Clinically Important Findings for Ophthalmic Examinations Anterior chamber hypopyon present, SE	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Potentially Clinically Important Findings for Ophthalmic Examinations Anterior chamber hypopyon present, FE	0 Participants	0 Participants	2 Participants	2 Participants	0 Participants	0 Participants	0 Participants
Summary of Potentially Clinically Important Findings for Ophthalmic Examinations Grade 2+ of Anterior chamber flare, SE	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Potentially Clinically Important Findings for Ophthalmic Examinations 2+ increases in Any Lens Opacity, SE	4 Participants	1 Participants	5 Participants	6 Participants	5 Participants	7 Participants	6 Participants
Summary of Potentially Clinically Important Findings for Ophthalmic Examinations VA =>15 loss from Baseline or Previous Visit, SE	15 Participants	8 Participants	7 Participants	9 Participants	9 Participants	16 Participants	5 Participants
Summary of Potentially Clinically Important Findings for Ophthalmic Examinations VA =>15 loss from Baseline or Previous Visit, FE	10 Participants	5 Participants	6 Participants	10 Participants	5 Participants	5 Participants	6 Participants

SECONDARY outcome

Timeframe: Up to week 52

Population: Safety Population

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.

Outcome measures

Measure	Placebo Control Arm QID n=73 Participants 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.	Pazopanib Eye Drops 5 mg/mL TID n=72 Participants 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.	Pazopanib Eye Drops 5 mg/mL QID n=74 Participants 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.	Pazopanib Eye Drops 10 mg/mL BID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL TID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL QID n=72 Participants 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.	Ranibizumab Injections Active Open-label Control Arm n=73 Participants 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.
Summary of Intraocular Pressure Exam Findings Any post-baseline IOP >=30 study eye	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	1 Participants	1 Participants
Summary of Intraocular Pressure Exam Findings IOP Lowering Medication for study eye	1 Participants	4 Participants	5 Participants	6 Participants	4 Participants	3 Participants	6 Participants
Summary of Intraocular Pressure Exam Findings IOP Lowering procedure for study eye	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Intraocular Pressure Exam Findings Any post-baseline IOP >=30 fellow eye	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	2 Participants
Summary of Intraocular Pressure Exam Findings IOP Lowering Medication for fellow eye	2 Participants	3 Participants	3 Participants	5 Participants	1 Participants	2 Participants	4 Participants
Summary of Intraocular Pressure Exam Findings IOP Lowering procedure for fellow eye	1 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Week 52

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

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.

Outcome measures

Measure	Placebo Control Arm QID n=73 Participants 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.	Pazopanib Eye Drops 5 mg/mL TID n=72 Participants 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.	Pazopanib Eye Drops 5 mg/mL QID n=74 Participants 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.	Pazopanib Eye Drops 10 mg/mL BID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL TID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL QID n=72 Participants 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.	Ranibizumab Injections Active Open-label Control Arm n=73 Participants 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.
Number of Participants With Vital Sign Values Outside of Clinical Concern Range Average diastolic blood pressure, Week 4, High	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Vital Sign Values Outside of Clinical Concern Range Average diastolic blood pressure, Week 4, Low	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Vital Sign Values Outside of Clinical Concern Range Average systolic blood pressure, Week 44, High	2 Participants	0 Participants	0 Participants	1 Participants	2 Participants	0 Participants	0 Participants
Number of Participants With Vital Sign Values Outside of Clinical Concern Range Heart Rate, Week 32, High	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Vital Sign Values Outside of Clinical Concern Range Average diastolic blood pressure, Week 8, High	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Vital Sign Values Outside of Clinical Concern Range Average diastolic blood pressure, Week 12, High	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	2 Participants	1 Participants
Number of Participants With Vital Sign Values Outside of Clinical Concern Range Average diastolic blood pressure, Week 16, High	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Vital Sign Values Outside of Clinical Concern Range Average diastolic blood pressure, Week 20, High	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Vital Sign Values Outside of Clinical Concern Range Average diastolic blood pressure, Week 24, High	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Vital Sign Values Outside of Clinical Concern Range Average diastolic blood pressure, Week 24, Low	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Vital Sign Values Outside of Clinical Concern Range Average diastolic blood pressure, Week 28, Low	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Vital Sign Values Outside of Clinical Concern Range Average diastolic blood pressure, Week 32, High	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Vital Sign Values Outside of Clinical Concern Range Average diastolic blood pressure, Week 36, Low	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Vital Sign Values Outside of Clinical Concern Range Average diastolic blood pressure, Week 44, High	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Vital Sign Values Outside of Clinical Concern Range Average diastolic blood pressure, Week 48, High	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Vital Sign Values Outside of Clinical Concern Range Average diastolic blood pressure, Week 52, High	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Vital Sign Values Outside of Clinical Concern Range Average systolic blood pressure, Day 1, High	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With Vital Sign Values Outside of Clinical Concern Range Average systolic blood pressure, Week 4, High	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Vital Sign Values Outside of Clinical Concern Range Average systolic blood pressure, Week 8, High	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Vital Sign Values Outside of Clinical Concern Range Average systolic blood pressure, Week 12, High	0 Participants	0 Participants	0 Participants	2 Participants	1 Participants	5 Participants	2 Participants
Number of Participants With Vital Sign Values Outside of Clinical Concern Range Average systolic blood pressure, Week 16, High	0 Participants	1 Participants	0 Participants	1 Participants	2 Participants	1 Participants	2 Participants
Number of Participants With Vital Sign Values Outside of Clinical Concern Range Average systolic blood pressure, Week 20, High	1 Participants	0 Participants	3 Participants	0 Participants	3 Participants	1 Participants	1 Participants
Number of Participants With Vital Sign Values Outside of Clinical Concern Range Average systolic blood pressure, Week 24, High	0 Participants	0 Participants	3 Participants	1 Participants	3 Participants	1 Participants	2 Participants
Number of Participants With Vital Sign Values Outside of Clinical Concern Range Average systolic blood pressure, Week 28, High	1 Participants	0 Participants	0 Participants	5 Participants	1 Participants	3 Participants	5 Participants
Number of Participants With Vital Sign Values Outside of Clinical Concern Range Average systolic blood pressure, Week 32, High	0 Participants	0 Participants	2 Participants	0 Participants	1 Participants	2 Participants	0 Participants
Number of Participants With Vital Sign Values Outside of Clinical Concern Range Average systolic blood pressure, Week 36, High	1 Participants	0 Participants	2 Participants	2 Participants	0 Participants	2 Participants	1 Participants
Number of Participants With Vital Sign Values Outside of Clinical Concern Range Average systolic blood pressure, Week 40, High	1 Participants	0 Participants	2 Participants	1 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Vital Sign Values Outside of Clinical Concern Range Average systolic blood pressure, Week 44, Low	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Vital Sign Values Outside of Clinical Concern Range Average systolic blood pressure, Week 48, High	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	2 Participants
Number of Participants With Vital Sign Values Outside of Clinical Concern Range Average systolic blood pressure, Week 52, High	2 Participants	2 Participants	2 Participants	1 Participants	2 Participants	2 Participants	2 Participants
Number of Participants With Vital Sign Values Outside of Clinical Concern Range Heart Rate, Week 16, High	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Vital Sign Values Outside of Clinical Concern Range Heart Rate, Week 20, High	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Vital Sign Values Outside of Clinical Concern Range Heart Rate, Week 24, High	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Vital Sign Values Outside of Clinical Concern Range Heart Rate, Week 36, High	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Vital Sign Values Outside of Clinical Concern Range Heart Rate, Week 40, High	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Vital Sign Values Outside of Clinical Concern Range Heart Rate, Week 48, High	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Week 4, Week 28, Week 44 and Week 52

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

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.

Outcome measures

Measure	Placebo Control Arm QID n=73 Participants 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.	Pazopanib Eye Drops 5 mg/mL TID n=72 Participants 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.	Pazopanib Eye Drops 5 mg/mL QID n=74 Participants 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.	Pazopanib Eye Drops 10 mg/mL BID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL TID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL QID n=72 Participants 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.	Ranibizumab Injections Active Open-label Control Arm n=73 Participants 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.
Summary of Abnormal Electrocardiogram (ECG) Findings Week 4, Abnormal - Not Clinically significant	24 Participants	25 Participants	25 Participants	25 Participants	24 Participants	31 Participants	27 Participants
Summary of Abnormal Electrocardiogram (ECG) Findings Week 28, Abnormal - Clinically significant	10 Participants	8 Participants	9 Participants	10 Participants	7 Participants	7 Participants	16 Participants
Summary of Abnormal Electrocardiogram (ECG) Findings Week 52, Abnormal - Not Clinically significant	23 Participants	29 Participants	25 Participants	21 Participants	24 Participants	22 Participants	20 Participants
Summary of Abnormal Electrocardiogram (ECG) Findings Week 4, Abnormal - Clinically significant	10 Participants	11 Participants	13 Participants	10 Participants	13 Participants	17 Participants	15 Participants
Summary of Abnormal Electrocardiogram (ECG) Findings Week 28, Abnormal - Not Clinically significant	21 Participants	22 Participants	17 Participants	22 Participants	18 Participants	25 Participants	18 Participants
Summary of Abnormal Electrocardiogram (ECG) Findings Week 44, Abnormal - Clinically significant	—	0 Participants	—	—	—	—	1 Participants
Summary of Abnormal Electrocardiogram (ECG) Findings Week 44, Abnormal - Not Clinically significant	—	1 Participants	—	—	—	—	0 Participants
Summary of Abnormal Electrocardiogram (ECG) Findings Week 52, Abnormal - Clinically significant	11 Participants	5 Participants	11 Participants	10 Participants	8 Participants	9 Participants	10 Participants

SECONDARY outcome

Timeframe: Up to Week 52

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

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.

Outcome measures

Measure	Placebo Control Arm QID n=73 Participants 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.	Pazopanib Eye Drops 5 mg/mL TID n=72 Participants 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.	Pazopanib Eye Drops 5 mg/mL QID n=74 Participants 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.	Pazopanib Eye Drops 10 mg/mL BID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL TID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL QID n=72 Participants 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.	Ranibizumab Injections Active Open-label Control Arm n=73 Participants 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.
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern ALT, Week 8, High	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Calcium, Week 4, High	1 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Calcium, Week 12, High	2 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Glucose, Day 1, Low	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Glucose, Week 4, High	2 Participants	3 Participants	3 Participants	4 Participants	2 Participants	2 Participants	3 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Platelet count, Week 52, High	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Potassium, Week 40, High	0 Participants	1 Participants	0 Participants	2 Participants	0 Participants	1 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern TSH, Day 1, High	2 Participants	2 Participants	3 Participants	3 Participants	2 Participants	1 Participants	1 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Total Bilirubin, Week 24, High	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Total Bilirubin, Week 32, High	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Total Bilirubin, Week 44, High	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern WBC, Week 52, High	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Total Neutrophils, Week 4, Low	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	1 Participants	1 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Total Neutrophils, Week 12, Low	1 Participants	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Total Neutrophils, Week 32, Low	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Total Neutrophils, Week 40, Low	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Total Neutrophils, Week 52, Low	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern BUN, Week 4, High	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern BUN, Week 16, High	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern BUN, Week 28, High	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern BUN, Week 40, High	0 Participants	0 Participants	0 Participants	3 Participants	0 Participants	0 Participants	1 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern WBC, DAy 1, Low	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Bicarbonate, Day 1, High	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Bicarbonate, Week4, Low	1 Participants	0 Participants	1 Participants	0 Participants	1 Participants	2 Participants	2 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Bicarbonate, Week 8, Low	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Bicarbonate, Week 12, Low	0 Participants	1 Participants	1 Participants	1 Participants	2 Participants	1 Participants	1 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Bicarbonate, Week 28, Low	3 Participants	1 Participants	0 Participants	0 Participants	0 Participants	4 Participants	1 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern ALT, Week 4, High	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern ALT, Week 12, High	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern ALT, Week 52, High	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Albumin, Week 4, Low	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Alkaline Phosphatase, Week 12, High	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Alkaline Phosphatase, Week 16, High	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Alkaline Phosphatase, Week 20, High	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Alkaline Phosphatase, Week 24, High	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern AST, Week 8, High	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern AST, Week 12, High	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern AST, Week 16, High	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern AST, Week 20, High	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern AST, Week 48, High	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Calcium, Day 1, High	2 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Bicarbonate, Week 32, Low	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Bicarbonate, Week 40, Low	0 Participants	1 Participants	1 Participants	1 Participants	0 Participants	1 Participants	1 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Bicarbonate, Week 52, Low	1 Participants	3 Participants	1 Participants	2 Participants	1 Participants	2 Participants	2 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Creatinine, Day 1, High	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Creatinine, Week 4, High	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Creatinine, Week 12, High	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	1 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Creatinine, Week 28, High	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Creatinine, Week 52, High	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Glucose, Day 1, High	6 Participants	5 Participants	3 Participants	3 Participants	1 Participants	3 Participants	7 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Glucose, Week 4, Low	0 Participants	1 Participants	2 Participants	0 Participants	0 Participants	1 Participants	2 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Glucose, Week 8, High	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Glucose, Week 12, High	3 Participants	5 Participants	3 Participants	2 Participants	4 Participants	2 Participants	8 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Glucose, Week 12, Low	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Glucose, Week 28, High	3 Participants	4 Participants	3 Participants	4 Participants	1 Participants	0 Participants	6 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Glucose, Week 28, Low	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Glucose, Week 32, High	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Glucose, Week 36, High	—	0 Participants	—	—	1 Participants	—	—
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Glucose, Week 40, High	6 Participants	7 Participants	4 Participants	5 Participants	1 Participants	3 Participants	9 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Glucose, Week 40, Low	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Glucose, Week 52, High	6 Participants	3 Participants	7 Participants	5 Participants	4 Participants	3 Participants	5 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Haemoglobin, Week 8, High	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Lymphocytes, Day 1, Low	1 Participants	3 Participants	3 Participants	3 Participants	3 Participants	0 Participants	1 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Lymphocytes, Week 4, Low	0 Participants	1 Participants	2 Participants	3 Participants	1 Participants	1 Participants	1 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Lymphocytes, Week 12, Low	2 Participants	0 Participants	2 Participants	2 Participants	2 Participants	2 Participants	1 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Lymphocytes, Week 28, Low	1 Participants	0 Participants	2 Participants	2 Participants	2 Participants	0 Participants	2 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Lymphocytes, Week 40, Low	2 Participants	1 Participants	3 Participants	4 Participants	0 Participants	1 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Lymphocytes, Week 52, Low	1 Participants	1 Participants	1 Participants	2 Participants	2 Participants	3 Participants	1 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Platelet count, Day 1, High	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Platelet count, Day 1, Low	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Platelet count, Week 4, High	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Platelet count, Week 4, Low	1 Participants	0 Participants	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Platelet count, Week 12, High	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	2 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Platelet count, Week 12, Low	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Platelet count, Week 28, High	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Platelet count, Week 28, Low	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Platelet count, Week 40, High	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Platelet count, Week 44, High	0 Participants	0 Participants	—	—	—	1 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Potassium, Day 1, High	1 Participants	3 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Potassium, Day 1, Low	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Potassium, Week 4, High	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	2 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Potassium, Week 4, Low	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Potassium, Week 12, High	3 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Potassium, Week 12, Low	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Potassium, Week 28, High	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Potassium, Week 52, High	1 Participants	0 Participants	1 Participants	0 Participants	2 Participants	1 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Sodium, Week 12, High	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Sodium, Week 40, Low	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Sodium, Week 52, Low	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern TSH, Week 12, High	1 Participants	1 Participants	2 Participants	1 Participants	1 Participants	3 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern TSH, Week 24, High	0 Participants	2 Participants	2 Participants	4 Participants	2 Participants	2 Participants	1 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern TSH, Week 36, High	1 Participants	2 Participants	3 Participants	5 Participants	3 Participants	2 Participants	2 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern TSH, Week 52, High	3 Participants	2 Participants	1 Participants	4 Participants	2 Participants	3 Participants	4 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Total Neutrophils, Day 1, Low	0 Participants	1 Participants	2 Participants	0 Participants	1 Participants	0 Participants	2 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Calcium, Week 28, High	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern Calcium, Week 52, Low	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern BUN, Day 1, High	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern BUN, Week 12, High	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	2 Participants	1 Participants
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern WBC, Week 28, Low	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Day 1 to Week 28 and Week 52

Population: Safety Population

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.

Outcome measures

Measure	Placebo Control Arm QID n=73 Participants 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.	Pazopanib Eye Drops 5 mg/mL TID n=72 Participants 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.	Pazopanib Eye Drops 5 mg/mL QID n=74 Participants 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.	Pazopanib Eye Drops 10 mg/mL BID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL TID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL QID n=72 Participants 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.	Ranibizumab Injections Active Open-label Control Arm n=73 Participants 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.
Number of Participants With Laboratory Data of Clinical Concern for Urine Protein Week 4	7 Participants	3 Participants	5 Participants	6 Participants	2 Participants	1 Participants	2 Participants
Number of Participants With Laboratory Data of Clinical Concern for Urine Protein Week 8	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Laboratory Data of Clinical Concern for Urine Protein Week 16	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Data of Clinical Concern for Urine Protein Week 28	7 Participants	5 Participants	4 Participants	8 Participants	4 Participants	2 Participants	6 Participants
Number of Participants With Laboratory Data of Clinical Concern for Urine Protein Week 32	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Data of Clinical Concern for Urine Protein Week 52	2 Participants	3 Participants	8 Participants	10 Participants	5 Participants	3 Participants	3 Participants

SECONDARY outcome

Timeframe: Week 4, Week 24 and Week 52

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

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.

Outcome measures

Measure	Placebo Control Arm QID n=72 Participants 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.	Pazopanib Eye Drops 5 mg/mL TID n=74 Participants 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.	Pazopanib Eye Drops 5 mg/mL QID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL BID n=73 Participants 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.	Pazopanib Eye Drops 10 mg/mL TID n=72 Participants 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.	Pazopanib Eye Drops 10 mg/mL QID 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.	Ranibizumab Injections Active Open-label Control Arm 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.
Plasma Concentrations of Pazopanib Week 4	80.20 nanogram/milliliter Interval 64.66 to 95.74	103.38 nanogram/milliliter Interval 89.68 to 117.08	93.82 nanogram/milliliter Interval 72.51 to 115.13	114.33 nanogram/milliliter Interval 96.77 to 131.9	175.89 nanogram/milliliter Interval 148.8 to 202.98	—	—
Plasma Concentrations of Pazopanib Week 24	81.94 nanogram/milliliter Interval 67.45 to 96.44	101.96 nanogram/milliliter Interval 86.1 to 117.82	104.88 nanogram/milliliter Interval 73.09 to 136.68	114.58 nanogram/milliliter Interval 96.71 to 132.45	183.32 nanogram/milliliter Interval 146.7 to 219.94	—	—
Plasma Concentrations of Pazopanib Week 52	NA nanogram/milliliter NA indicates, data not quantifiable because the concentration was below limit of quantification.	44.04 nanogram/milliliter Only one participant was available at the time of analysis, confidence interval could not be calculated.	60.98 nanogram/milliliter Interval -79.29 to 201.25	28.77 nanogram/milliliter Interval -227.64 to 285.18	40.33 nanogram/milliliter Only one participant was available at the time of analysis, confidence interval could not be calculated.	—	—

Adverse Events

Placebo Control Arm QID

Serious events: 11 serious events

Other events: 52 other events

Deaths: 2 deaths

Pazopanib Eye Drops 5 mg/mL TID

Serious events: 10 serious events

Other events: 34 other events

Deaths: 1 deaths

Pazopanib Eye Drops 5 mg/mL QID

Serious events: 12 serious events

Other events: 47 other events

Deaths: 1 deaths

Pazopanib Eye Drops 10 mg/mL BID

Serious events: 11 serious events

Other events: 44 other events

Deaths: 0 deaths

Pazopanib Eye Drops 10 mg/mL TID

Serious events: 10 serious events

Other events: 46 other events

Deaths: 3 deaths

Pazopanib Eye Drops 10 mg/mL QID

Serious events: 11 serious events

Other events: 41 other events

Deaths: 0 deaths

Ranibizumab Injections Active Open-label Control Arm

Serious events: 6 serious events

Other events: 42 other events

Deaths: 1 deaths

Serious adverse events

Measure	Placebo Control Arm QID n=73 participants at risk 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.	Pazopanib Eye Drops 5 mg/mL TID n=72 participants at risk 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.	Pazopanib Eye Drops 5 mg/mL QID n=74 participants at risk 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.	Pazopanib Eye Drops 10 mg/mL BID n=73 participants at risk 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.	Pazopanib Eye Drops 10 mg/mL TID n=73 participants at risk 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.	Pazopanib Eye Drops 10 mg/mL QID n=72 participants at risk 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.	Ranibizumab Injections Active Open-label Control Arm n=73 participants at risk 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.
Nervous system disorders Cerebrovascular accident	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Nervous system disorders Syncope	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Nervous system disorders Transient ischaemic attack	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Nervous system disorders Ataxia	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Nervous system disorders Brain Stem Stroke	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Nervous system disorders Cerebral haemorrhage	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Nervous system disorders Cervical myelopathy	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Nervous system disorders Encephalopathy	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Gastrointestinal disorders Abdominal pain	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.8% 2/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Gastrointestinal disorders Abdominal hernia	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Gastrointestinal disorders Colitis	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Gastrointestinal disorders Crohn's disease	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Gastrointestinal disorders Duodenal ulcer	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Gastrointestinal disorders Gastric ulcer haemorrhage	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Gastrointestinal disorders Gastritis	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Gastrointestinal disorders Intestinal perforation	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Infections and infestations Cellulitis	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Infections and infestations Endophthalmitis	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Infections and infestations Pneumonia	2.7% 2/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Infections and infestations Abscess intestinal	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Infections and infestations Erysipelas	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Infections and infestations Gastroenteritis	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Infections and infestations Infection	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Infections and infestations Periorbital cellulitis	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer metastatic	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon neoplasm	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal cancer metastatic	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung cancer metastatic	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm malignant	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian cancer	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Injury, poisoning and procedural complications Cartilage injury	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Injury, poisoning and procedural complications Pelvic fracture	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Injury, poisoning and procedural complications Post procedural complication	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Injury, poisoning and procedural complications Post-traumatic neck syndrome	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Injury, poisoning and procedural complications Rib fracture	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Injury, poisoning and procedural complications Spinal cord injury	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Cardiac disorders Angina pectoris	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.7% 2/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Cardiac disorders Atrioventricular block second degree	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Cardiac disorders Cardiac failure congestive	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Cardiac disorders Coronary artery disease	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Cardiac disorders Mitral valve disease	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Cardiac disorders Myocardial infarction	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Metabolism and nutrition disorders Fluid overload	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Metabolism and nutrition disorders Hypercalcaemia	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Metabolism and nutrition disorders Hyperkalaemia	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Metabolism and nutrition disorders Hyponatraemia	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Renal and urinary disorders Hypertensive nephropathy	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Renal and urinary disorders Renal artery stenosis	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Renal and urinary disorders Renal cyst haemorrhage	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Renal and urinary disorders Renal failure acute	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Hepatobiliary disorders Bile duct obstruction	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Hepatobiliary disorders Bile duct stone	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Hepatobiliary disorders Cholecystitis acute	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Hepatobiliary disorders Cholelithiasis	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Vascular disorders Aortic aneurysm	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Vascular disorders Hypertension	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Vascular disorders Shock	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Ear and labyrinth disorders Vertigo	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.8% 2/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Reproductive system and breast disorders Prostatomegaly	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Congenital, familial and genetic disorders Haemorrhagic arteriovenous malformation	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Eye disorders Retinal haemorrhage	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
General disorders Device failure	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Investigations Prothrombin time prolonged	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Blood and lymphatic system disorders Iron deficiency anaemia	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Nervous system disorders Myasthenia gravis	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.

Other adverse events

Measure	Placebo Control Arm QID n=73 participants at risk 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.	Pazopanib Eye Drops 5 mg/mL TID n=72 participants at risk 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.	Pazopanib Eye Drops 5 mg/mL QID n=74 participants at risk 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.	Pazopanib Eye Drops 10 mg/mL BID n=73 participants at risk 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.	Pazopanib Eye Drops 10 mg/mL TID n=73 participants at risk 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.	Pazopanib Eye Drops 10 mg/mL QID n=72 participants at risk 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.	Ranibizumab Injections Active Open-label Control Arm n=73 participants at risk 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.
Infections and infestations Bronchitis	4.1% 3/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.7% 2/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.7% 2/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	5.5% 4/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.8% 2/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	5.5% 4/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Infections and infestations Nasopharyngitis	15.1% 11/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	6.9% 5/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	8.1% 6/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	23.3% 17/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	6.8% 5/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	18.1% 13/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	6.8% 5/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Vascular disorders Hypertension	4.1% 3/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	5.6% 4/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	6.8% 5/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	5.5% 4/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	8.2% 6/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	8.3% 6/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	9.6% 7/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Infections and infestations Urinary tract infection	12.3% 9/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	4.2% 3/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	8.2% 6/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	8.2% 6/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	5.6% 4/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	4.1% 3/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Eye disorders Conjunctival haemorrhage	6.8% 5/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.8% 2/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	9.6% 7/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	8.2% 6/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	8.3% 6/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.7% 2/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Respiratory, thoracic and mediastinal disorders Cough	11.0% 8/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	4.2% 3/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	8.1% 6/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	5.5% 4/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.7% 2/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	4.2% 3/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	4.1% 3/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Nervous system disorders Headache	4.1% 3/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.8% 2/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	6.8% 5/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	6.8% 5/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	9.7% 7/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	8.2% 6/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Eye disorders Vitreous floaters	4.1% 3/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.8% 2/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.7% 2/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	4.1% 3/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.7% 2/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	4.2% 3/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	5.5% 4/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Eye disorders Retinal haemorrhage	6.8% 5/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	4.2% 3/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	4.1% 3/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.7% 2/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	5.5% 4/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	4.2% 3/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	5.5% 4/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Eye disorders Visual acuity reduced	4.1% 3/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	4.2% 3/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.7% 2/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	8.2% 6/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	4.2% 3/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	5.5% 4/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Musculoskeletal and connective tissue disorders Back pain	6.8% 5/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.8% 2/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	6.8% 5/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.7% 2/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	5.5% 4/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.8% 2/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Eye disorders Eye pain	9.6% 7/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	5.5% 4/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.8% 2/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	6.8% 5/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Infections and infestations Upper respiratory tract infection	2.7% 2/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	8.1% 6/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.7% 2/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	5.5% 4/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	4.2% 3/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	4.1% 3/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Gastrointestinal disorders Diarrhoea	5.5% 4/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	4.2% 3/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.7% 2/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	6.8% 5/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.7% 2/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	4.2% 3/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Infections and infestations Sinusitis	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	5.4% 4/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	4.1% 3/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	5.6% 4/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	6.8% 5/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Eye disorders Vision blurred	5.5% 4/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.7% 2/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.7% 2/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	5.5% 4/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.8% 2/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.7% 2/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Infections and infestations Influenza	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	6.9% 5/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.7% 2/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	4.1% 3/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	4.1% 3/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	4.1% 3/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
General disorders Pain	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	5.6% 4/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.7% 2/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	4.1% 3/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.7% 2/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	4.2% 3/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Musculoskeletal and connective tissue disorders Pain in extremity	2.7% 2/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	4.2% 3/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	5.4% 4/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.7% 2/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.7% 2/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	4.2% 3/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Gastrointestinal disorders Nausea	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	4.1% 3/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	4.1% 3/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	5.6% 4/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	4.1% 3/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Musculoskeletal and connective tissue disorders Arthralgia	2.7% 2/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.8% 2/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.7% 2/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	4.2% 3/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	5.5% 4/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Eye disorders Blepharitis	2.7% 2/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	4.1% 3/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	4.1% 3/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	5.5% 4/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Injury, poisoning and procedural complications Fall	2.7% 2/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	5.6% 4/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.7% 2/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.7% 2/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.7% 2/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Eye disorders Punctate keratitis	5.5% 4/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	4.1% 3/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	4.2% 3/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Immune system disorders Seasonal allergy	4.1% 3/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	5.4% 4/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.7% 2/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.7% 2/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Eye disorders Lacrimation increased	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.7% 2/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	6.9% 5/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Nervous system disorders Dizziness	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	6.9% 5/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	4.1% 3/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Blood and lymphatic system disorders Anaemia	4.1% 3/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	5.5% 4/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.8% 2/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Eye disorders Conjunctivitis	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.7% 2/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	8.3% 6/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Eye disorders Dry eye	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	5.6% 4/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
General disorders Injection site haemorrhage	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.7% 2/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	5.5% 4/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Infections and infestations Pneumonia	2.7% 2/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	5.4% 4/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	4.1% 3/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Eye disorders Conjunctival hyperaemia	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	5.4% 4/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	2.7% 2/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Eye disorders Cataract cortical	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	5.4% 4/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.
Skin and subcutaneous tissue disorders Rash	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/74 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	1.4% 1/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	5.5% 4/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/72 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.	0.00% 0/73 • All AEs and SAEs were collected during the treatment period (up to 52 weeks) All AEs and SAEs were reported on Safety Population.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER