Trial Outcomes & Findings for A Long-Term Safety Study Evaluating the Safety and Systemic Exposure of AR-15512 (NCT NCT05493111)

NCT ID: NCT05493111

Last Updated: 2025-08-13

Results Overview

A treatment-emergent adverse event was defined as any event that occurred or worsened on or after the day randomized study intervention was initiated. At each study visit, subjects were verbally asked by clinic staff to report any changes to any aspect of their ocular health. Ocular treatment-emergent adverse events reported by the subject or observed by the investigator were summarized by preferred term for overall incidence calculation. This was a subject-based assessment.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 275 participants
• Primary outcome timeframe: Day 1 post-treatment, up to Day 365
• Results posted on: 2025-08-13

Participant Flow

Subjects were recruited from 10 investigative sites located in the United States.

This reporting group includes all subjects who signed an informed consent and met all eligibility criteria.

Unit of analysis: eyes

Participant milestones

Measure	0.003% AR-15512 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Overall Study STARTED	182 364	93 186
Overall Study COMPLETED	149 298	76 152
Overall Study NOT COMPLETED	33 66	17 34

Reasons for withdrawal

Measure	0.003% AR-15512 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Overall Study Adverse Event	3	4
Overall Study Withdrawal of Consent	19	10
Overall Study Non-compliance	1	1
Overall Study Lost to Follow-up	8	1
Overall Study Disallowed Concurrent Treatment	1	0
Overall Study Withdrawal by Subject	1	1

Baseline Characteristics

A Long-Term Safety Study Evaluating the Safety and Systemic Exposure of AR-15512

Baseline characteristics by cohort

Measure	0.003% AR-15512 n=182 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=93 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	Total n=275 Participants Total of all reporting groups
Age, Continuous	61.2 years STANDARD_DEVIATION 14.46 • n=5 Participants	59.1 years STANDARD_DEVIATION 15.42 • n=7 Participants	60.5 years STANDARD_DEVIATION 14.79 • n=5 Participants
Age, Customized 18-29 years	5 subjects n=5 Participants	4 subjects n=7 Participants	9 subjects n=5 Participants
Age, Customized 30 to 45 years	23 subjects n=5 Participants	16 subjects n=7 Participants	39 subjects n=5 Participants
Age, Customized 46-60 years	44 subjects n=5 Participants	23 subjects n=7 Participants	67 subjects n=5 Participants
Age, Customized 61-75 years	81 subjects n=5 Participants	42 subjects n=7 Participants	123 subjects n=5 Participants
Age, Customized Greater than 75 years	29 subjects n=5 Participants	8 subjects n=7 Participants	37 subjects n=5 Participants
Sex: Female, Male Female	130 Participants n=5 Participants	65 Participants n=7 Participants	195 Participants n=5 Participants
Sex: Female, Male Male	52 Participants n=5 Participants	28 Participants n=7 Participants	80 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	37 Participants n=5 Participants	21 Participants n=7 Participants	58 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	145 Participants n=5 Participants	72 Participants n=7 Participants	217 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	2 subjects n=5 Participants	0 subjects n=7 Participants	2 subjects n=5 Participants
Race/Ethnicity, Customized Asian	16 subjects n=5 Participants	10 subjects n=7 Participants	26 subjects n=5 Participants
Race/Ethnicity, Customized Black or African American	23 subjects n=5 Participants	14 subjects n=7 Participants	37 subjects n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 subjects n=5 Participants	0 subjects n=7 Participants	1 subjects n=5 Participants
Race/Ethnicity, Customized White	138 subjects n=5 Participants	67 subjects n=7 Participants	205 subjects n=5 Participants
Race/Ethnicity, Customized Multi-racial	0 subjects n=5 Participants	0 subjects n=7 Participants	0 subjects n=5 Participants
Race/Ethnicity, Customized Other	2 subjects n=5 Participants	2 subjects n=7 Participants	4 subjects n=5 Participants

PRIMARY outcome

Timeframe: Day 1 post-treatment, up to Day 365

Population: Safety Population

A treatment-emergent adverse event was defined as any event that occurred or worsened on or after the day randomized study intervention was initiated. At each study visit, subjects were verbally asked by clinic staff to report any changes to any aspect of their ocular health. Ocular treatment-emergent adverse events reported by the subject or observed by the investigator were summarized by preferred term for overall incidence calculation. This was a subject-based assessment.

Outcome measures

Measure	0.003% AR-15512 n=182 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=93 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Ocular Treatment-Emergent Adverse Events by Preferred Term With Incidence Greater Than 2 Percent Instillation site pain	90 adverse event	7 adverse event	—	—
Ocular Treatment-Emergent Adverse Events by Preferred Term With Incidence Greater Than 2 Percent Eye pruritis	2 adverse event	3 adverse event	—	—
Ocular Treatment-Emergent Adverse Events by Preferred Term With Incidence Greater Than 2 Percent Eyelid margin crusting	1 adverse event	2 adverse event	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365

Population: Safety Population with data at baseline and corresponding visit

Heart rate was measured using manual or automated methods and recorded in beats per minute (bpm). Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=175 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=88 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Heart Rate at Each Study Visit Change from Baseline at Day 14	0.7 beats per minute Standard Deviation 9.06	0.6 beats per minute Standard Deviation 8.51	—	—
Mean Change From Baseline in Heart Rate at Each Study Visit Change from Baseline at Day 90	1.4 beats per minute Standard Deviation 9.04	1.7 beats per minute Standard Deviation 10.93	—	—
Mean Change From Baseline in Heart Rate at Each Study Visit Change from Baseline at Day 180	0.5 beats per minute Standard Deviation 9.20	-0.9 beats per minute Standard Deviation 9.71	—	—
Mean Change From Baseline in Heart Rate at Each Study Visit Change from Baseline at Day 270	0.8 beats per minute Standard Deviation 9.57	0.5 beats per minute Standard Deviation 9.34	—	—
Mean Change From Baseline in Heart Rate at Each Study Visit Change from Baseline at Day 365	1.1 beats per minute Standard Deviation 9.73	1.0 beats per minute Standard Deviation 10.00	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365

Population: Safety Population with data at baseline and corresponding visit

Systolic blood pressure was measured using an appropriate sphygmomanometer and recorded in millimeters mercury (mmHg). Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=175 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=88 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Systolic Blood Pressure at Each Study Visit Change from Baseline at Day 14	1.4 mmHg Standard Deviation 16.62	1.7 mmHg Standard Deviation 14.40	—	—
Mean Change From Baseline in Systolic Blood Pressure at Each Study Visit Change from Baseline at Day 90	0.0 mmHg Standard Deviation 14.27	1.2 mmHg Standard Deviation 14.65	—	—
Mean Change From Baseline in Systolic Blood Pressure at Each Study Visit Change from Baseline at Day 180	-3.3 mmHg Standard Deviation 15.23	0.1 mmHg Standard Deviation 17.19	—	—
Mean Change From Baseline in Systolic Blood Pressure at Each Study Visit Change from Baseline at Day 270	-1.3 mmHg Standard Deviation 14.98	-1.8 mmHg Standard Deviation 16.38	—	—
Mean Change From Baseline in Systolic Blood Pressure at Each Study Visit Change from Baseline at Day 365	0.1 mmHg Standard Deviation 16.25	-0.3 mmHg Standard Deviation 13.65	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365

Population: Safety Population with data at baseline and corresponding visit

Diastolic blood pressure was measured using an appropriate sphygmomanometer and recorded in millimeters mercury (mmHg). Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=175 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=88 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Diastolic Blood Pressure at Each Study Visit Change from Baseline at Day 14	1.7 mmHg Standard Deviation 9.29	0.6 mmHg Standard Deviation 9.81	—	—
Mean Change From Baseline in Diastolic Blood Pressure at Each Study Visit Change from Baseline at Day 90	0.2 mmHg Standard Deviation 9.73	1.1 mmHg Standard Deviation 9.63	—	—
Mean Change From Baseline in Diastolic Blood Pressure at Each Study Visit Change from Baseline at Day 180	1.1 mmHg Standard Deviation 9.01	1.6 mmHg Standard Deviation 9.96	—	—
Mean Change From Baseline in Diastolic Blood Pressure at Each Study Visit Change from Baseline at Day 270	0.8 mmHg Standard Deviation 9.63	0.5 mmHg Standard Deviation 9.83	—	—
Mean Change From Baseline in Diastolic Blood Pressure at Each Study Visit Change from Baseline at Day 365	1.4 mmHg Standard Deviation 9.56	1.3 mmHg Standard Deviation 9.23	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 365

Population: Safety Population with data at baseline and corresponding visit

Cell density in the central corneal endothelium was assessed using specular microscopy imaging. Overall average cell density was calculated as the average of the average cell densities of three images and was measured in cells per millimeter squared (cells/mm^2). A negative change from baseline represents a less desirable outcome.

Outcome measures

Measure	0.003% AR-15512 n=145 eyes 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=146 eyes AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye n=76 eyes AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye n=76 eyes AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Overall Average Endothelial Cell Density at Day 365	12.8 cells/mm^2 Standard Deviation 204.06	32.4 cells/mm^2 Standard Deviation 203.12	-40.4 cells/mm^2 Standard Deviation 172.29	-15.7 cells/mm^2 Standard Deviation 162.02

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Study Exit (Day 365, early termination visit, or unscheduled visit)

Population: Safety Population with data at baseline and corresponding visit

Cell density in the central corneal endothelium was assessed using specular microscopy imaging. Overall average cell density was calculated as the average of the average cell densities of three images and was measured in cells per millimeter squared (cells/mm^2). A decrease from baseline represents a less desirable outcome.

Outcome measures

Measure	0.003% AR-15512 n=151 eyes 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=152 eyes AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye n=79 eyes AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye n=79 eyes AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Percentage of Subjects With 10 Percent or More Decrease From Baseline in Overall Average Endothelial Cell Density at Study Exit	3.3 percentage of subjects	2.6 percentage of subjects	5.1 percentage of subjects	2.5 percentage of subjects

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 180, Day 365

Population: Safety Population with data at baseline and corresponding visit

A small volume of blood was collected and sent to a laboratory for analysis. Basophil level was measured. Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=135 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=64 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Hematology by Visit - Basophil Level Change from Baseline at Day 180	0.00 10^9 cells per liter (10^9 cells/L) Standard Deviation 0.057	-0.01 10^9 cells per liter (10^9 cells/L) Standard Deviation 0.052	—	—
Mean Change From Baseline in Hematology by Visit - Basophil Level Change from Baseline at Day 365	-0.01 10^9 cells per liter (10^9 cells/L) Standard Deviation 0.053	-0.01 10^9 cells per liter (10^9 cells/L) Standard Deviation 0.048	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 180, Day 365

Population: Safety Population with data at baseline and corresponding visit

A small volume of blood was collected and sent to a laboratory for analysis. The basophils to leukocytes ratio was reported as the absolute number of basophils divided by the absolute number of leukocytes multiplied by 100. Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=135 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=64 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Hematology by Visit - Basophils to Leukocytes Ratio Reported in Percentage of Cells Change from Baseline at Day 180	0.03 percentage of cells Standard Deviation 0.256	0.02 percentage of cells Standard Deviation 0.291	—	—
Mean Change From Baseline in Hematology by Visit - Basophils to Leukocytes Ratio Reported in Percentage of Cells Change from Baseline at Day 365	-0.05 percentage of cells Standard Deviation 0.217	-0.02 percentage of cells Standard Deviation 0.238	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 180, Day 365

Population: Safety Population with data at baseline and corresponding visit

A small volume of blood was collected and sent to a laboratory for analysis. Eosinophil level was measured. Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=135 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=64 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Hematology by Visit - Eosinophil Level Change from Baseline at Day 180	0.02 10^9 cells/L Standard Deviation 0.143	0.01 10^9 cells/L Standard Deviation 0.084	—	—
Mean Change From Baseline in Hematology by Visit - Eosinophil Level Change from Baseline at Day 365	0.02 10^9 cells/L Standard Deviation 0.150	0.00 10^9 cells/L Standard Deviation 0.076	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 180, Day 365

Population: Safety Population with data at baseline and corresponding visit

A small volume of blood was collected and sent to a laboratory for analysis. The eosinophils to leukocytes ratio was reported as the absolute number of eosinophils divided by the absolute number of leukocytes multiplied by 100. Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=135 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=64 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Hematology by Visit - Eosinophils to Leukocytes Ratio Reported in Percentage of Cells Change from Baseline at Day 180	0.29 percentage of cells Standard Deviation 1.626	0.20 percentage of cells Standard Deviation 1.468	—	—
Mean Change From Baseline in Hematology by Visit - Eosinophils to Leukocytes Ratio Reported in Percentage of Cells Change from Baseline at Day 365	0.34 percentage of cells Standard Deviation 2.081	0.13 percentage of cells Standard Deviation 1.333	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 180, Day 365

Population: Safety Population with data at baseline and corresponding visit

A small volume of blood was collected and sent to a laboratory for analysis. Erythrocyte mean corpuscular hemoglobin concentration level was measured. Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=136 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=64 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Hematology by Visit - Erythrocyte Mean Corpuscular Hemoglobin Concentration Level Change from Baseline at Day 180	-2.0 grams per liter (g/L) Standard Deviation 9.45	-1.3 grams per liter (g/L) Standard Deviation 8.71	—	—
Mean Change From Baseline in Hematology by Visit - Erythrocyte Mean Corpuscular Hemoglobin Concentration Level Change from Baseline at Day 365	1.2 grams per liter (g/L) Standard Deviation 8.76	0.9 grams per liter (g/L) Standard Deviation 9.74	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 180, Day 365

Population: Safety Population with data at baseline and corresponding visit

A small volume of blood was collected and sent to a laboratory for analysis. Erythrocyte mean corpuscular hemoglobin level was measured. Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=136 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=64 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Hematology by Visit - Erythrocyte Mean Corpuscular Hemoglobin Level Change from Baseline at Day 180	-0.01 picograms (pg) Standard Deviation 1.020	0.01 picograms (pg) Standard Deviation 0.609	—	—
Mean Change From Baseline in Hematology by Visit - Erythrocyte Mean Corpuscular Hemoglobin Level Change from Baseline at Day 365	0.21 picograms (pg) Standard Deviation 0.877	0.26 picograms (pg) Standard Deviation 0.905	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 180, Day 365

Population: Safety Population with data at baseline and corresponding visit

A small volume of blood was collected and sent to a laboratory for analysis. Erythrocyte mean corpuscular volume was measured. Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=136 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=64 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Hematology by Visit - Erythrocyte Mean Corpuscular Volume Change from Baseline at Day 180	0.53 femtoliters (fL) Standard Deviation 2.996	0.33 femtoliters (fL) Standard Deviation 2.548	—	—
Mean Change From Baseline in Hematology by Visit - Erythrocyte Mean Corpuscular Volume Change from Baseline at Day 365	0.28 femtoliters (fL) Standard Deviation 2.449	0.50 femtoliters (fL) Standard Deviation 2.684	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 180, Day 365

Population: Safety Population with data at baseline and corresponding visit

A small volume of blood was collected and sent to a laboratory for analysis. Erythrocyte level was measured. Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=136 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=64 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Hematology by Visit - Erythrocyte Level Change from Baseline at Day 180	-0.071 10^12 cells per liter (10^12 cells/L) Standard Deviation 0.2858	-0.036 10^12 cells per liter (10^12 cells/L) Standard Deviation 0.2738	—	—
Mean Change From Baseline in Hematology by Visit - Erythrocyte Level Change from Baseline at Day 365	-0.073 10^12 cells per liter (10^12 cells/L) Standard Deviation 0.2873	-0.076 10^12 cells per liter (10^12 cells/L) Standard Deviation 0.2347	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 180, Day 365

Population: Safety Population with data at baseline and corresponding visit

A small volume of blood was collected and sent to a laboratory for analysis. Erythrocyte distribution width was measured. Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=136 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=64 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Hematology by Visit - Erythrocyte Distribution Width Reported as Percentage of Variation of Cells Change from Baseline at Day 180	0.09 percentage of variation of cells Standard Deviation 1.038	0.13 percentage of variation of cells Standard Deviation 0.721	—	—
Mean Change From Baseline in Hematology by Visit - Erythrocyte Distribution Width Reported as Percentage of Variation of Cells Change from Baseline at Day 365	-0.02 percentage of variation of cells Standard Deviation 0.924	-0.17 percentage of variation of cells Standard Deviation 0.666	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 180, Day 365

Population: Safety Population with data at baseline and corresponding visit

A small volume of blood was collected and sent to a laboratory for analysis. Hematocrit level was reported as the volume of red blood cells in liters (L) divided by the volume of blood in L. Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=136 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=64 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Hematology by Visit - Hematocrit Level Change from Baseline at Day 180	-0.0038 proportion Standard Deviation 0.02449	-0.0020 proportion Standard Deviation 0.02580	—	—
Mean Change From Baseline in Hematology by Visit - Hematocrit Level Change from Baseline at Day 365	-0.0053 proportion Standard Deviation 0.02723	-0.0051 proportion Standard Deviation 0.02443	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 180, Day 365

Population: Safety Population with data at baseline and corresponding visit

A small volume of blood was collected and sent to a laboratory for analysis. Hemoglobin level was measured. Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=136 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=64 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Hematology by Visit - Hemoglobin Level Change from Baseline at Day 180	-2.1 g/L Standard Deviation 7.94	-1.1 g/L Standard Deviation 8.38	—	—
Mean Change From Baseline in Hematology by Visit - Hemoglobin Level Change from Baseline at Day 365	-1.3 g/L Standard Deviation 8.69	-1.3 g/L Standard Deviation 7.91	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 180, Day 365

Population: Safety Population with data at baseline and corresponding visit

A small volume of blood was collected and sent to a laboratory for analysis. Leukocyte level was measured. Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=136 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=64 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Hematology by Visit - Leukocyte Level Change from Baseline at Day 180	-0.06 10^9 cells/L Standard Deviation 1.653	-0.46 10^9 cells/L Standard Deviation 1.054	—	—
Mean Change From Baseline in Hematology by Visit - Leukocyte Level Change from Baseline at Day 365	-0.12 10^9 cells/L Standard Deviation 1.351	-0.38 10^9 cells/L Standard Deviation 1.342	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 180, Day 365

Population: Safety Population with data at baseline and corresponding visit

A small volume of blood was collected and sent to a laboratory for analysis. Lymphocyte level was measured. Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=135 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=64 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Hematology by Visit - Lymphocyte Level Change from Baseline at Day 180	-0.28 10^9 cells/L Standard Deviation 0.500	-0.28 10^9 cells/L Standard Deviation 0.522	—	—
Mean Change From Baseline in Hematology by Visit - Lymphocyte Level Change from Baseline at Day 365	-0.18 10^9 cells/L Standard Deviation 0.417	-0.32 10^9 cells/L Standard Deviation 0.466	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 180, Day 365

Population: Safety Population with data at baseline and corresponding visit

A small volume of blood was collected and sent to a laboratory for analysis. The lymphocytes to leukocytes ratio was reported as the absolute number of lymphocytes divided by the absolute number of leukocytes multiplied by 100. Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=135 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=64 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Hematology by Visit - Lymphocytes to Leukocytes Ratio Reported in Percentage of Cells Change from Baseline at Day 180	-3.21 percentage of cells Standard Deviation 6.934	-1.76 percentage of cells Standard Deviation 6.713	—	—
Mean Change From Baseline in Hematology by Visit - Lymphocytes to Leukocytes Ratio Reported in Percentage of Cells Change from Baseline at Day 365	-1.95 percentage of cells Standard Deviation 6.664	-2.20 percentage of cells Standard Deviation 6.544	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 180, Day 365

Population: Safety Population with data at baseline and corresponding visit

A small volume of blood was collected and sent to a laboratory for analysis. Monocyte level was measured. Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=135 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=64 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Hematology by Visit - Monocyte Level Change from Baseline at Day 180	-0.02 10^9 cells/L Standard Deviation 0.148	-0.03 10^9 cells/L Standard Deviation 0.145	—	—
Mean Change From Baseline in Hematology by Visit - Monocyte Level Change from Baseline at Day 365	-0.01 10^9 cells/L Standard Deviation 0.167	-0.01 10^9 cells/L Standard Deviation 0.185	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 180, Day 365

Population: Safety Population with data at baseline and corresponding visit

A small volume of blood was collected and sent to a laboratory for analysis. The monocytes to leukocytes ratio was reported as the absolute number of monocytes divided by the absolute number of leukocytes multiplied by 100. Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=135 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=64 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Hematology by Visit - Monocytes to Leukocytes Ratio Reported in Percentage of Cells Change from Baseline at Day 180	-0.10 percentage of cells Standard Deviation 2.100	0.21 percentage of cells Standard Deviation 2.005	—	—
Mean Change From Baseline in Hematology by Visit - Monocytes to Leukocytes Ratio Reported in Percentage of Cells Change from Baseline at Day 365	0.09 percentage of cells Standard Deviation 2.182	0.25 percentage of cells Standard Deviation 2.040	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 180, Day 365

Population: Safety Population with data at baseline and corresponding visit

A small volume of blood was collected and sent to a laboratory for analysis. Neutrophil level was measured. Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=135 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=64 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Hematology by Visit - Neutrophil Level Change from Baseline at Day 180	0.20 10^9 cells/L Standard Deviation 1.532	-0.17 10^9 cells/L Standard Deviation 0.912	—	—
Mean Change From Baseline in Hematology by Visit - Neutrophil Level Change from Baseline at Day 365	0.05 10^9 cells/L Standard Deviation 1.208	-0.05 10^9 cells/L Standard Deviation 1.197	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 180, Day 365

Population: Safety Population with data at baseline and corresponding visit

A small volume of blood was collected and sent to a laboratory for analysis. The neutrophils to leukocytes ratio was reported as the absolute number of neutrophils divided by the absolute number of leukocytes multiplied by 100. Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=135 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=64 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Hematology by Visit - Neutrophils to Leukocytes Ratio Reported in Percentage of Cells Change from Baseline at Day 180	3.00 percentage of cells Standard Deviation 8.231	1.32 percentage of cells Standard Deviation 8.546	—	—
Mean Change From Baseline in Hematology by Visit - Neutrophils to Leukocytes Ratio Reported in Percentage of Cells Change from Baseline at Day 365	1.58 percentage of cells Standard Deviation 8.055	1.84 percentage of cells Standard Deviation 7.839	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 180, Day 365

Population: Safety Population with data at baseline and corresponding visit

A small volume of blood was collected and sent to a laboratory for analysis. Platelet level was measured. Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=135 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=63 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Hematology by Visit - Platelet Level Change from Baseline at Day 180	-3.9 10^9 cells/L Standard Deviation 42.18	-9.0 10^9 cells/L Standard Deviation 40.42	—	—
Mean Change From Baseline in Hematology by Visit - Platelet Level Change from Baseline at Day 365	-3.7 10^9 cells/L Standard Deviation 32.58	-1.5 10^9 cells/L Standard Deviation 39.96	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 180, Day 365

Population: Safety Population with data at baseline and corresponding visit

A small volume of blood was collected and sent to a laboratory for analysis. Platelet volume was measured. Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=135 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=64 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Hematology by Visit - Mean Platelet Volume Change from Baseline at Day 180	-0.24 fL Standard Deviation 0.511	-0.15 fL Standard Deviation 0.559	—	—
Mean Change From Baseline in Hematology by Visit - Mean Platelet Volume Change from Baseline at Day 365	-0.04 fL Standard Deviation 0.479	-0.24 fL Standard Deviation 0.433	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 180, Day 365

Population: Safety Population with data at baseline and corresponding visit

A small volume of blood was collected and sent to a laboratory for analysis. Alanine aminotransferase level was measured. Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=145 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=71 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Chemistry by Visit - Alanine Aminotransferase Level Change from Baseline at Day 180	0.3 units per liter (U/L) Standard Deviation 15.01	-2.5 units per liter (U/L) Standard Deviation 12.11	—	—
Mean Change From Baseline in Chemistry by Visit - Alanine Aminotransferase Level Change from Baseline at Day 365	-0.2 units per liter (U/L) Standard Deviation 13.38	-1.4 units per liter (U/L) Standard Deviation 12.59	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 180, Day 365

Population: Safety Population with data at baseline and corresponding visit

A small volume of blood was collected and sent to a laboratory for analysis. Albumin level was measured. Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=148 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=73 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Chemistry by Visit - Albumin Level Change from Baseline at Day 180	-2.0 g/L Standard Deviation 2.37	-1.9 g/L Standard Deviation 2.56	—	—
Mean Change From Baseline in Chemistry by Visit - Albumin Level Change from Baseline at Day 365	-2.1 g/L Standard Deviation 2.35	-2.1 g/L Standard Deviation 2.30	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 180, Day 365

Population: Safety Population with data at baseline and corresponding visit

A small volume of blood was collected and sent to a laboratory for analysis. Alkaline phosphatase level was measured. Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=148 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=73 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Chemistry by Visit - Alkaline Phosphatase Level Change from Baseline at Day 180	2.5 U/L Standard Deviation 13.12	0.4 U/L Standard Deviation 16.66	—	—
Mean Change From Baseline in Chemistry by Visit - Alkaline Phosphatase Level Change from Baseline at Day 365	-1.3 U/L Standard Deviation 16.12	-3.5 U/L Standard Deviation 13.59	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 180, Day 365

Population: Safety Population with data at baseline and corresponding visit

A small volume of blood was collected and sent to a laboratory for analysis. Aspartate aminotransferase level was measured. Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=145 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=71 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Chemistry by Visit - Aspartate Aminotransferase Level Change from Baseline at Day 180	0.6 U/L Standard Deviation 14.74	-0.1 U/L Standard Deviation 7.80	—	—
Mean Change From Baseline in Chemistry by Visit - Aspartate Aminotransferase Level Change from Baseline at Day 365	0.0 U/L Standard Deviation 11.98	0.1 U/L Standard Deviation 9.39	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 180, Day 365

Population: Safety Population with data at baseline and corresponding visit

A small volume of blood was collected and sent to a laboratory for analysis. Calcium level was measured. Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=148 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=73 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Chemistry by Visit - Calcium Level Change from Baseline at Day 180	-0.044 millimoles per liter (mmol/L) Standard Deviation 0.1051	-0.037 millimoles per liter (mmol/L) Standard Deviation 0.1026	—	—
Mean Change From Baseline in Chemistry by Visit - Calcium Level Change from Baseline at Day 365	-0.049 millimoles per liter (mmol/L) Standard Deviation 0.1114	-0.055 millimoles per liter (mmol/L) Standard Deviation 0.0923	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 180, Day 365

Population: Safety Population with data at baseline and corresponding visit

A small volume of blood was collected and sent to a laboratory for analysis. Creatinine level was measured. Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=148 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=73 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Chemistry by Visit - Creatinine Level Change from Baseline at Day 180	1.3 micromoles per liter (Umol/L) Standard Deviation 13.69	-0.2 micromoles per liter (Umol/L) Standard Deviation 12.38	—	—
Mean Change From Baseline in Chemistry by Visit - Creatinine Level Change from Baseline at Day 365	6.0 micromoles per liter (Umol/L) Standard Deviation 60.26	1.3 micromoles per liter (Umol/L) Standard Deviation 10.00	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 180, Day 365

Population: Safety Population with data at baseline and corresponding visit

A small volume of blood was collected and sent to a laboratory for analysis. Globulin level was measured. Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=148 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=73 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Chemistry by Visit - Globulin Level Change from Baseline at Day 180	0.3 g/L Standard Deviation 2.61	0.5 g/L Standard Deviation 2.44	—	—
Mean Change From Baseline in Chemistry by Visit - Globulin Level Change from Baseline at Day 365	0.0 g/L Standard Deviation 2.43	-0.1 g/L Standard Deviation 2.05	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 180, Day 365

Population: Safety Population with data at baseline and corresponding visit

A small volume of blood was collected and sent to a laboratory for analysis. Potassium level was measured. Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=133 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=69 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Chemistry by Visit - Potassium Level Change from Baseline at Day 180	0.09 mmol/L Standard Deviation 0.492	0.11 mmol/L Standard Deviation 0.482	—	—
Mean Change From Baseline in Chemistry by Visit - Potassium Level Change from Baseline at Day 365	0.06 mmol/L Standard Deviation 0.470	0.16 mmol/L Standard Deviation 0.704	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 180, Day 365

Population: Safety Population with data at baseline and corresponding visit

A small volume of blood was collected and sent to a laboratory for analysis. Protein level was measured. Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=148 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=73 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Chemistry by Visit - Protein Level Change from Baseline at Day 180	-1.7 g/L Standard Deviation 4.19	-1.4 g/L Standard Deviation 4.15	—	—
Mean Change From Baseline in Chemistry by Visit - Protein Level Change from Baseline at Day 365	-2.1 g/L Standard Deviation 3.97	-2.2 g/L Standard Deviation 3.67	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 180, Day 365

Population: Safety Population with data at baseline and corresponding visit

A small volume of blood was collected and sent to a laboratory for analysis. Sodium level was measured. Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=148 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=73 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Chemistry by Visit - Sodium Level Change from Baseline at Day 180	0.0 mmol/L Standard Deviation 2.46	-0.1 mmol/L Standard Deviation 2.17	—	—
Mean Change From Baseline in Chemistry by Visit - Sodium Level Change from Baseline at Day 365	0.4 mmol/L Standard Deviation 2.36	0.5 mmol/L Standard Deviation 2.11	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 180, Day 365

Population: Safety Population with data at baseline and corresponding visit

A small volume of blood was collected and sent to a laboratory for analysis. Triglyceride level was measured. Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=148 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=73 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Chemistry by Visit - Triglyceride Level Change from Baseline at Day 180	0.079 mmol/L Standard Deviation 1.1354	-0.276 mmol/L Standard Deviation 1.1943	—	—
Mean Change From Baseline in Chemistry by Visit - Triglyceride Level Change from Baseline at Day 365	-0.024 mmol/L Standard Deviation 0.9164	-0.120 mmol/L Standard Deviation 1.2344	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 180, Day 365

Population: Safety Population with data at baseline and corresponding visit

A small volume of blood was collected and sent to a laboratory for analysis. Urea nitrogen level was measured. Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=148 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=72 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Chemistry by Visit - Urea Nitrogen Level Change from Baseline at Day 180	0.22 mmol/L Standard Deviation 2.066	0.06 mmol/L Standard Deviation 1.889	—	—
Mean Change From Baseline in Chemistry by Visit - Urea Nitrogen Level Change from Baseline at Day 365	0.16 mmol/L Standard Deviation 2.372	0.044 mmol/L Standard Deviation 1.637	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 180, Day 365

Population: Safety Population with data at baseline and corresponding visit

A small volume of blood was collected and sent to a laboratory for analysis. Specific gravity level was calculated by dividing the sample's density by the density of water. Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=140 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=66 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Urinalysis by Visit - Specific Gravity Level Change from Baseline at Day 180	0.0005 ratio Standard Deviation 0.00783	0.0020 ratio Standard Deviation 0.00713	—	—
Mean Change From Baseline in Urinalysis by Visit - Specific Gravity Level Change from Baseline at Day 365	0.0007 ratio Standard Deviation 0.00886	0.0019 ratio Standard Deviation 0.00732	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 180, Day 365

Population: Safety Population with data at baseline and corresponding visit

A small volume of urine was collected and sent to a laboratory for analysis. The pH scale ranges from 0 (most acidic) to 14 (most alkaline), with 7 as neutral. Minimal change from the start of the study indicates a better outcome.

Outcome measures

Measure	0.003% AR-15512 n=140 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=66 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Change From Baseline in Urinalysis by Visit - pH Level Change from Baseline at Day 180	0.06 pH Standard Deviation 0.882	-0.02 pH Standard Deviation 0.857	—	—
Mean Change From Baseline in Urinalysis by Visit - pH Level Change from Baseline at Day 365	0.05 pH Standard Deviation 0.712	0.03 pH Standard Deviation 0.769	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 365

Population: Safety Population with data at visit

Visual acuity with correction in place (spectacles or a trial frame with lenses) was measured using Early Treatment Diabetic Retinopathy Study (ETDRS) letter charts (original or modified) at a distance of 10 feet. Each line on the ETDRS chart typically has five letters, and each letter correctly identified adds to the overall score. ETDRS letter scores range from 0 to 100, with each letter correctly identified representing a score of 1. A perfect score of 100 is achieved when all 70 letters on the chart are correctly identified. 85 letters correctly identified corresponds to normal distance eyesight.

Outcome measures

Measure	0.003% AR-15512 n=181 eyes 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=181 eyes AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye n=93 eyes AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye n=93 eyes AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Best Corrected Visual Acuity (BCVA) Letter Score by Visit Baseline	84.9 letter Standard Deviation 5.38	84.7 letter Standard Deviation 6.05	85.8 letter Standard Deviation 5.19	84.9 letter Standard Deviation 5.91
Mean Best Corrected Visual Acuity (BCVA) Letter Score by Visit Day 365	85.1 letter Standard Deviation 6.23	84.6 letter Standard Deviation 7.15	84.9 letter Standard Deviation 5.89	84.1 letter Standard Deviation 5.90

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365

Population: Safety Population with data at visit

Visual acuity with correction in place (spectacles or a trial frame with lenses) was measured using Early Treatment Diabetic Retinopathy Study (ETDRS) letter charts (original or modified) at a distance of 10 feet. Each line on the ETDRS chart typically has five letters, and each letter correctly identified adds to the overall score. The overall letter score was converted to Logarithmic minimum angle of resolution (LogMAR). LogMAR scores typically range from -0.3 to 1.0, where zero represents normal vision, negative values indicate better than normal vision, and positive values indicate poorer than normal vision.

Outcome measures

Measure	0.003% AR-15512 n=182 eyes 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=182 eyes AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye n=93 eyes AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye n=93 eyes AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Corrected Visual Acuity in LogMar by Visit Baseline	0.062 logMAR Standard Deviation 0.1326	0.061 logMAR Standard Deviation 0.1339	0.064 logMAR Standard Deviation 0.1433	0.080 logMAR Standard Deviation 0.1435
Mean Corrected Visual Acuity in LogMar by Visit Day 14	0.055 logMAR Standard Deviation 0.1386	0.053 logMAR Standard Deviation 0.1406	0.048 logMAR Standard Deviation 0.1334	0.053 logMAR Standard Deviation 0.1481
Mean Corrected Visual Acuity in LogMar by Visit Day 90	0.046 logMAR Standard Deviation 0.1315	0.044 logMAR Standard Deviation 0.1279	0.048 logMAR Standard Deviation 0.1339	0.049 logMAR Standard Deviation 0.1268
Mean Corrected Visual Acuity in LogMar by Visit Day 180	0.047 logMAR Standard Deviation 0.1304	0.045 logMAR Standard Deviation 0.1298	0.042 logMAR Standard Deviation 0.1523	0.051 logMAR Standard Deviation 0.1548
Mean Corrected Visual Acuity in LogMar by Visit Day 270	0.076 logMAR Standard Deviation 0.1364	0.070 logMAR Standard Deviation 0.1288	0.065 logMAR Standard Deviation 0.1461	0.092 logMAR Standard Deviation 0.1458
Mean Corrected Visual Acuity in LogMar by Visit Day 365	0.063 logMAR Standard Deviation 0.1183	0.060 logMAR Standard Deviation 0.1244	0.080 logMAR Standard Deviation 0.1523	0.084 logMAR Standard Deviation 0.1460

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365

Population: Safety Population with data at visit

An eye exam (slit lamp biomicroscopy) was performed by the investigator at each study visit. Findings related to lid erythema (redness of the eyelid) were graded as Normal or Abnormal. Abnormal findings were categorized as clinically significant (CS) or not clinically significant (NCS). CS findings were defined at those that may interfere with study parameters or otherwise confound the data as determined by the investigator.

Outcome measures

Measure	0.003% AR-15512 n=182 eye 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=182 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye n=93 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye n=93 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Lid Erythema Baseline	1 subjects	1 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Lid Erythema 88Day 14	0 subjects	0 subjects	0 subjects	1 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Lid Erythema Day 90	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Lid Erythema Day 180	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Lid Erythema Day 270	0 subjects	0 subjects	0 subjects	1 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Lid Erythema Day 365	0 subjects	0 subjects	0 subjects	0 subjects

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365

Population: Safety Population with data at visit

An eye exam (slit lamp biomicroscopy) was performed by the investigator at each study visit. Findings related to lid edema (swelling of the eyelid) were graded as Normal or Abnormal. Abnormal findings were categorized as clinically significant (CS) or not clinically significant (NCS). CS findings were defined at those that may interfere with study parameters or otherwise confound the data as determined by the investigator.

Outcome measures

Measure	0.003% AR-15512 n=182 eye 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=182 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye n=93 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye n=93 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Lid Edema Baseline	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Lid Edema Day 14	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Lid Edema Day 90	1 subjects	1 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Lid Edema Day 180	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Lid Edema Day 270	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Lid Edema Day 365	0 subjects	0 subjects	0 subjects	0 subjects

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365

Population: Safety Population with data at visit

An eye exam (slit lamp biomicroscopy) was performed by the investigator at each study visit. Findings related to conjunctiva hyperemia (increased amount of blood in the conjunctiva) were graded as Normal or Abnormal. Abnormal findings were categorized as clinically significant (CS) or not clinically significant (NCS). CS findings were defined at those that may interfere with study parameters or otherwise confound the data as determined by the investigator.

Outcome measures

Measure	0.003% AR-15512 n=182 eye 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=182 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye n=93 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye n=93 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Conjunctiva Hyperemia Baseline	2 subjects	2 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Conjunctiva Hyperemia Day 14	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Conjunctiva Hyperemia Day 90	1 subjects	1 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Conjunctiva Hyperemia Day 180	0 subjects	0 subjects	1 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Conjunctiva Hyperemia Day 270	1 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Conjunctiva Hyperemia Day 365	0 subjects	0 subjects	0 subjects	0 subjects

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365

Population: Safety Population with data at visit

An eye exam (slit lamp biomicroscopy) was performed by the investigator at each study visit. Findings related to conjunctiva edema (swelling of the conjunctiva) were graded as Normal or Abnormal. Abnormal findings were categorized as clinically significant (CS) or not clinically significant (NCS). CS findings were defined at those that may interfere with study parameters or otherwise confound the data as determined by the investigator.

Outcome measures

Measure	0.003% AR-15512 n=182 eye 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=182 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye n=93 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye n=93 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Conjunctiva Edema Baseline	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Conjunctiva Edema Day 14	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Conjunctiva Edema Day 90	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Conjunctiva Edema Day 180	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Conjunctiva Edema Day 270	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Conjunctiva Edema Day 365	0 subjects	0 subjects	0 subjects	0 subjects

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365

Population: Safety Population with data at visit

An eye exam (slit lamp biomicroscopy) was performed by the investigator at each study visit. Findings related to cornea staining/erosion were graded as Normal or Abnormal. Abnormal findings were categorized as clinically significant (CS) or not clinically significant (NCS). CS findings were defined at those that may interfere with study parameters or otherwise confound the data as determined by the investigator.

Outcome measures

Measure	0.003% AR-15512 n=182 eye 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=182 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye n=93 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye n=93 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Cornea Staining/Erosion Baseline	2 subjects	2 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Cornea Staining/Erosion Day 14	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Cornea Staining/Erosion Day 90	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Cornea Staining/Erosion Day 180	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Cornea Staining/Erosion Day 270	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Cornea Staining/Erosion Day 365	0 subjects	0 subjects	0 subjects	0 subjects

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365

Population: Safety Population with data at visit

An eye exam (slit lamp biomicroscopy) was performed by the investigator at each study visit. Findings related to cornea edema (swelling of the cornea) were graded as Normal or Abnormal. Abnormal findings were categorized as clinically significant (CS) or not clinically significant (NCS). CS findings were defined at those that may interfere with study parameters or otherwise confound the data as determined by the investigator.

Outcome measures

Measure	0.003% AR-15512 n=182 eye 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=182 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye n=93 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye n=93 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Cornea Edema Baseline	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Cornea Edema Day 14	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Cornea Edema Day 90	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Cornea Edema Day 180	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Cornea Edema Day 270	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Cornea Edema Day 365	0 subjects	0 subjects	0 subjects	0 subjects

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365

Population: Safety Population with data at visit

An eye exam (slit lamp biomicroscopy) was performed by the investigator at each study visit. Findings related to cells in the anterior chamber (the fluid-filled space located in the front of the eye between the cornea and the iris) were graded as Normal or Abnormal. Abnormal findings were categorized as clinically significant (CS) or not clinically significant (NCS). CS findings were defined at those that may interfere with study parameters or otherwise confound the data as determined by the investigator.

Outcome measures

Measure	0.003% AR-15512 n=182 eye 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=182 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye n=93 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye n=93 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Anterior Chamber Cells Baseline	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Anterior Chamber Cells Day 14	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Anterior Chamber Cells Day 90	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Anterior Chamber Cells Day 180	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Anterior Chamber Cells Day 270	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Anterior Chamber Cells Day 365	0 subjects	0 subjects	0 subjects	0 subjects

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365

Population: Safety Population with data at visit

An eye exam (slit lamp biomicroscopy) was performed by the investigator at each study visit. Findings related to anterior chamber flare (a visible clouding of the the fluid-filled space located in the front of the eye between the cornea and the iris) were graded as Normal or Abnormal. Abnormal findings were categorized as clinically significant (CS) or not clinically significant (NCS). CS findings were defined at those that may interfere with study parameters or otherwise confound the data as determined by the investigator.

Outcome measures

Measure	0.003% AR-15512 n=182 eye 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=182 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye n=93 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye n=93 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Anterior Chamber Flare Baseline	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Anterior Chamber Flare Day 14	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Anterior Chamber Flare Day 90	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Anterior Chamber Flare Day 180	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Anterior Chamber Flare Day 270	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Anterior Chamber Flare Day 365	0 subjects	0 subjects	0 subjects	0 subjects

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365

Population: Safety Population with natural lens intact (phakic) and data at visit

An eye exam (slit lamp biomicroscopy) was performed by the investigator at each study visit. Findings related to lens opacity (a clouding of the eye's natural lens) were graded as Normal or Abnormal. Abnormal findings were categorized as clinically significant (CS) or not clinically significant (NCS). CS findings were defined at those that may interfere with study parameters or otherwise confound the data as determined by the investigator.

Outcome measures

Measure	0.003% AR-15512 n=137 eye 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=137 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye n=74 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye n=74 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Lens Opacity Baseline	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Lens Opacity Day 14	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Lens Opacity Day 90	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Lens Opacity Day 180	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Lens Opacity Day 270	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Lens Opacity Day 365	0 subjects	0 subjects	0 subjects	0 subjects

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365

Population: Safety Population with data at visit

Total corneal (fluorescein) staining score ranges between 0 and 5. Total conjunctival staining score is collected as the sum of lissamine green staining nasal and temporal scores and ranges between 0 and 10 per eye. Total ocular staining score is collected as the sum of total corneal and conjunctival scores (0 to 15) with a maximum possible score of 15 per eye. A higher total score indicates greater staining (or worse condition).

Outcome measures

Measure	0.003% AR-15512 n=182 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=182 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye n=93 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye n=93 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Total Ocular Staining Score by Visit Baseline	4.08 score on a scale Standard Deviation 2.167	4.36 score on a scale Standard Deviation 2.332	3.77 score on a scale Standard Deviation 2.163	4.02 score on a scale Standard Deviation 2.352
Mean Total Ocular Staining Score by Visit Day 14	3.46 score on a scale Standard Deviation 2.339	3.70 score on a scale Standard Deviation 2.395	3.45 score on a scale Standard Deviation 2.368	3.64 score on a scale Standard Deviation 2.400
Mean Total Ocular Staining Score by Visit Day 90	2.91 score on a scale Standard Deviation 2.415	3.17 score on a scale Standard Deviation 2.543	2.97 score on a scale Standard Deviation 2.674	3.27 score on a scale Standard Deviation 2.815
Mean Total Ocular Staining Score by Visit Day 180	2.74 score on a scale Standard Deviation 2.493	2.85 score on a scale Standard Deviation 2.518	2.65 score on a scale Standard Deviation 2.477	3.05 score on a scale Standard Deviation 2.663
Mean Total Ocular Staining Score by Visit Day 270	2.45 score on a scale Standard Deviation 2.513	2.78 score on a scale Standard Deviation 2.556	2.53 score on a scale Standard Deviation 2.524	2.86 score on a scale Standard Deviation 2.516
Mean Total Ocular Staining Score by Visit Day 365	2.97 score on a scale Standard Deviation 2.841	2.97 score on a scale Standard Deviation 2.625	2.89 score on a scale Standard Deviation 2.619	3.30 score on a scale Standard Deviation 2.807

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365

Population: Safety Population with data at visit

Intraocular pressure was measured using Goldmann applanation tonometry and measured in millimeters mercury (mmHg). Values between 10mmHg and 20mmHg are considered normal eye pressure.

Outcome measures

Measure	0.003% AR-15512 n=182 eye 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=182 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye n=93 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye n=93 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Mean Intraocular Pressure by Visit Baseline	15.4 mmHg Standard Deviation 2.48	15.6 mmHg Standard Deviation 2.57	15.5 mmHg Standard Deviation 2.75	15.6 mmHg Standard Deviation 2.71
Mean Intraocular Pressure by Visit Day 14	15.5 mmHg Standard Deviation 2.82	15.6 mmHg Standard Deviation 2.85	15.6 mmHg Standard Deviation 2.81	15.5 mmHg Standard Deviation 2.86
Mean Intraocular Pressure by Visit 9Day 90	15.6 mmHg Standard Deviation 2.52	15.5 mmHg Standard Deviation 2.61	15.2 mmHg Standard Deviation 2.72	15.0 mmHg Standard Deviation 2.86
Mean Intraocular Pressure by Visit Day 180	15.5 mmHg Standard Deviation 2.62	15.7 mmHg Standard Deviation 2.62	14.8 mmHg Standard Deviation 2.68	14.8 mmHg Standard Deviation 2.66
Mean Intraocular Pressure by Visit Day 270	15.3 mmHg Standard Deviation 2.66	15.5 mmHg Standard Deviation 2.49	15.1 mmHg Standard Deviation 2.79	15.2 mmHg Standard Deviation 2.98
Mean Intraocular Pressure by Visit Day 365	15.4 mmHg Standard Deviation 2.55	15.4 mmHg Standard Deviation 2.77	15.4 mmHg Standard Deviation 3.15	15.5 mmHg Standard Deviation 3.06

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365

Population: Safety Population with data at baseline and corresponding visit

An examination of the back of the eye (dilated fundus exam) was performed by the investigator. Findings related to the vitreous (the clear gel that fills the space between the lens and the retina of the eyeball) were graded as Normal or Abnormal. Abnormal findings were categorized as clinically significant (CS) or not clinically significant (NCS). CS findings were defined at those that may interfere with study parameters or otherwise confound the data as determined by the investigator.

Outcome measures

Measure	0.003% AR-15512 n=174 eye 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=174 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye n=88 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye n=88 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Number of Subjects With Clinically Significant Change From Baseline in Dilated Fundus Exam Results by Visit - Vitreous Clinically Significant Change from Baseline at Day 14	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Change From Baseline in Dilated Fundus Exam Results by Visit - Vitreous Clinically Significant Change from Baseline at Day 90	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Change From Baseline in Dilated Fundus Exam Results by Visit - Vitreous Clinically Significant Change from Baseline at Day 180	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Change From Baseline in Dilated Fundus Exam Results by Visit - Vitreous Clinically Significant Change from Baseline at Day 270	0 subjects	0 subjects	1 subjects	0 subjects
Number of Subjects With Clinically Significant Change From Baseline in Dilated Fundus Exam Results by Visit - Vitreous Clinically Significant Change from Baseline at Day 365	0 subjects	0 subjects	1 subjects	0 subjects

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365

Population: Safety Population with data at baseline and corresponding visit

An examination of the back of the eye (dilated fundus exam) was performed by the investigator. Findings related to the retina (the light-sensitive tissue lining the back of the eye that converts light into electrical signals the brain then interprets as images) were graded as Normal or Abnormal. Abnormal findings were categorized as clinically significant (CS) or not clinically significant (NCS). CS findings were defined at those that may interfere with study parameters or otherwise confound the data as determined by the investigator.

Outcome measures

Measure	0.003% AR-15512 n=174 eye 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=174 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye n=88 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye n=88 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Number of Subjects With Clinically Significant Change From Baseline in Dilated Fundus Exam Results by Visit - Retina Clinically Significant Change from Baseline at Day 14	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Change From Baseline in Dilated Fundus Exam Results by Visit - Retina Clinically Significant Change from Baseline at Day 90	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Change From Baseline in Dilated Fundus Exam Results by Visit - Retina Clinically Significant Change from Baseline at Day 180	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Change From Baseline in Dilated Fundus Exam Results by Visit - Retina Clinically Significant Change from Baseline at Day 270	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Change From Baseline in Dilated Fundus Exam Results by Visit - Retina Clinically Significant Change from Baseline at Day 365	0 subjects	0 subjects	0 subjects	1 subjects

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365

Population: Safety Population with data at baseline and corresponding visit

An examination of the back of the eye (dilated fundus exam) was performed by the investigator. Findings related to the macula (the round area at the center of the retina that provides central vision) were graded as Normal or Abnormal. Abnormal findings were categorized as clinically significant (CS) or not clinically significant (NCS). CS findings were defined at those that may interfere with study parameters or otherwise confound the data as determined by the investigator.

Outcome measures

Measure	0.003% AR-15512 n=174 eye 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=174 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye n=88 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye n=88 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Number of Subjects With Clinically Significant Change From Baseline in Dilated Fundus Exam Results by Visit - Macula Clinically Significant Change from Baseline at Day 14	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Change From Baseline in Dilated Fundus Exam Results by Visit - Macula Clinically Significant Change from Baseline at Day 90	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Change From Baseline in Dilated Fundus Exam Results by Visit - Macula Clinically Significant Change from Baseline at Day 180	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Change From Baseline in Dilated Fundus Exam Results by Visit - Macula Clinically Significant Change from Baseline at Day 270	0 subjects	0 subjects	1 subjects	0 subjects
Number of Subjects With Clinically Significant Change From Baseline in Dilated Fundus Exam Results by Visit - Macula Clinically Significant Change from Baseline at Day 365	0 subjects	0 subjects	1 subjects	0 subjects

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365

Population: Safety Population with data at baseline and corresponding visit

An examination of the back of the eye (dilated fundus exam) was performed by the investigator. Findings related to the optic nerve (the nerve that transmits visual information from the retina to the brain) were graded as Normal or Abnormal. Abnormal findings were categorized as clinically significant (CS) or not clinically significant (NCS). CS findings were defined at those that may interfere with study parameters or otherwise confound the data as determined by the investigator.

Outcome measures

Measure	0.003% AR-15512 n=174 eye 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=174 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye n=88 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye n=88 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Number of Subjects With Clinically Significant Change From Baseline in Dilated Fundus Exam Results by Visit - Optic Nerve Clinically Significant Change from Baseline at Day 14	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Change From Baseline in Dilated Fundus Exam Results by Visit - Optic Nerve Clinically Significant Change from Baseline at Day 90	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Change From Baseline in Dilated Fundus Exam Results by Visit - Optic Nerve Clinically Significant Change from Baseline at Day 180	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Change From Baseline in Dilated Fundus Exam Results by Visit - Optic Nerve Clinically Significant Change from Baseline at Day 270	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Change From Baseline in Dilated Fundus Exam Results by Visit - Optic Nerve Clinically Significant Change from Baseline at Day 365	0 subjects	0 subjects	0 subjects	0 subjects

PRIMARY outcome

Timeframe: Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365

Population: Safety Population with data at baseline and corresponding visit

An examination of the back of the eye (dilated fundus exam) was performed by the investigator. Findings related to the choroid (the layer of blood vessels and connective tissue between the white of the eye and retina) were graded as Normal or Abnormal. Abnormal findings were categorized as clinically significant (CS) or not clinically significant (NCS). CS findings were defined at those that may interfere with study parameters or otherwise confound the data as determined by the investigator.

Outcome measures

Measure	0.003% AR-15512 n=174 eye 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle n=174 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Right Eye n=88 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle - Left Eye n=88 eye AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Number of Subjects With Clinically Significant Change From Baseline in Dilated Fundus Exam Results by Visit - Choroid Clinically Significant Change from Baseline at Day 365	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Change From Baseline in Dilated Fundus Exam Results by Visit - Choroid Clinically Significant Change from Baseline at Day 14	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Change From Baseline in Dilated Fundus Exam Results by Visit - Choroid Clinically Significant Change from Baseline at Day 90	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Change From Baseline in Dilated Fundus Exam Results by Visit - Choroid Clinically Significant Change from Baseline at Day 180	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Clinically Significant Change From Baseline in Dilated Fundus Exam Results by Visit - Choroid Clinically Significant Change from Baseline at Day 270	0 subjects	0 subjects	0 subjects	0 subjects

Adverse Events

0.003% AR-15512 Ocular

Serious events: 1 serious events

Other events: 90 other events

Deaths: 0 deaths

0.003% AR-15512 Non-ocular

Serious events: 6 serious events

Other events: 0 other events

Deaths: 0 deaths

AR-15512 Vehicle Ocular

Serious events: 2 serious events

Other events: 7 other events

Deaths: 0 deaths

AR-15512 Vehicle Non-ocular

Serious events: 6 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	0.003% AR-15512 Ocular n=182 participants at risk 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	0.003% AR-15512 Non-ocular n=182 participants at risk 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle Ocular n=93 participants at risk AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle Non-ocular n=93 participants at risk AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
Eye disorders Neovascular age-related macular degeneration	0.00% 0/182 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	1.1% 1/93 • Number of events 1 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.
Eye disorders Retinal detachment	0.00% 0/182 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	1.1% 1/93 • Number of events 1 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.
Eye disorders Retinal tear	0.55% 1/182 • Number of events 1 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	0.00% 0/93 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.
Gastrointestinal disorders Small intestinal obstruction	— 0/0 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	0.00% 0/182 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	1.1% 1/93 • Number of events 1 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.
Hepatobiliary disorders Cholelithiasis	— 0/0 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	0.55% 1/182 • Number of events 1 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	0.00% 0/93 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.
Infections and infestations Cellulitis	— 0/0 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	0.00% 0/182 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	1.1% 1/93 • Number of events 1 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.
Infections and infestations Pneumonia aspiration	— 0/0 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	0.00% 0/182 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	1.1% 1/93 • Number of events 1 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.
Injury, poisoning and procedural complications Face injury	— 0/0 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	0.55% 1/182 • Number of events 1 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	0.00% 0/93 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.
Injury, poisoning and procedural complications Head injury	— 0/0 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	0.00% 0/182 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	1.1% 1/93 • Number of events 1 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.
Injury, poisoning and procedural complications Spinal fracture	— 0/0 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	0.00% 0/182 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	1.1% 1/93 • Number of events 1 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.
Metabolism and nutrition disorders Dehydration	— 0/0 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	0.00% 0/182 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	1.1% 1/93 • Number of events 1 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	— 0/0 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	0.55% 1/182 • Number of events 1 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	1.1% 1/93 • Number of events 1 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	— 0/0 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	0.55% 1/182 • Number of events 1 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	0.00% 0/93 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	— 0/0 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	0.55% 1/182 • Number of events 1 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	0.00% 0/93 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.
Nervous system disorders Cerebrovascular accident	— 0/0 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	0.55% 1/182 • Number of events 1 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	0.00% 0/93 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.
Nervous system disorders Syncope	— 0/0 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	0.00% 0/182 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	1.1% 1/93 • Number of events 1 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.
Vascular disorders Hypotension	— 0/0 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	0.55% 1/182 • Number of events 1 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	0.00% 0/93 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.

Other adverse events

Measure	0.003% AR-15512 Ocular n=182 participants at risk 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	0.003% AR-15512 Non-ocular n=182 participants at risk 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle Ocular n=93 participants at risk AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	AR-15512 Vehicle Non-ocular n=93 participants at risk AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
General disorders Instillation site pain	49.5% 90/182 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	7.5% 7/93 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered to be related to the study intervention. AEs were collected from time of consent until study exit, approximately 1 year. On the day of consent, randomized treatment was initiated. All participants were monitored for serious and other ocular and non-ocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the non-ocular AE arms were not considered at risk for ocular adverse event terms as the arms are reporting non-ocular-specific AEs. Similarly, the ocular AE arms were not considered at risk for non-ocular adverse event terms as the arms are reporting ocular-specific AEs.

Additional Information

Scientific Advisor, Clinical Research and Development

Alcon Research, LLC

Phone: 1-888-451-3937

Email: alcon.medinfo@alcon.com

Results disclosure agreements

• Principal investigator is a sponsor employee Sponsor reserves the right of prior review of any publication or presentation of information related to the study.
• Publication restrictions are in place

Restriction type: OTHER