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

Phase 3

Completed

Conditions: Dry Eye Disease

Interventions: Drug: 0.003% AR-15512 ophthalmic solution
Drug: AR-15512 vehicle ophthalmic solution

Registration Number: NCT05493111

Lead Sponsor: Aerie Pharmaceuticals

Brief Summary: The purpose of this study is to evaluate the safety of topical ophthalmic 0.003% AR-15512 compared to its vehicle dosed twice daily (BID) in subjects with dry eye disease (DED) for 12 months.

Detailed Description: At the end of the Screening Visit, subjects will undergo a protocol-specified washout period for prohibited prior and concomitant therapies. At the Baseline Visit, subjects who qualify based on inclusion/exclusion criteria will be enrolled in the study and randomized in a 2:1 ratio to receive 0.003% AR-15512 or AR-15512 Vehicle administered as 1 drop in each eye twice a day for 365 days (12 months). At the end of the Day 365 visit, subjects will exit the study.

Aerie Pharmaceuticals was acquired by Alcon on November 22, 2022.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 275

Inclusion Criteria

Previous history of Dry Eye Disease (DED) within the previous 12 months of the Baseline visit.
Have used or desired to use artificial tears for DED symptoms within 3 months prior to the Baseline visit.
Corrected visual acuity as specified in the protocol at the Baseline visit.
Good general and ocular health, as determined by the investigator using medical history, ophthalmic examination and history, and vital signs (heart rate and blood pressure) at the Baseline visit.

Key

Exclusion Criteria

History or presence of any ocular disorder or condition (other than DED) in either eye that would, in the opinion of the investigator, likely interfere with the interpretation of the study results or subject safety.
Current evidence of other significant ophthalmic disease requiring topical medication (e.g. glaucoma, ocular hypertension) which may interfere with vision (e.g., cataract, macular degeneration) or other disease which the investigator believes may interfere with study findings or interpretation.
Use of contact lenses in either eye within 7 days prior to the Baseline visit or planned use during the study.
Use of medications as specified in the protocol.
Use of lid heating therapy (i.e., LipiFlow®, iLUX®) or Meibomian gland probing/therapeutic expression within 6 months prior to the Baseline visit or anticipated during the study.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
0.003% AR-15512	0.003% AR-15512 ophthalmic solution	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	AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days
0.003% AR-15512	0.003% AR-15512 ophthalmic solution	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	AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days

Primary Outcome Measures

Name	Time	Method
Ocular Treatment-Emergent Adverse Events by Preferred Term With Incidence Greater Than 2 Percent	Day 1 post-treatment, up to Day 365	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.
Mean Change From Baseline in Heart Rate at Each Study Visit	Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365	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.
Mean Change From Baseline in Systolic Blood Pressure at Each Study Visit	Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365	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.
Mean Change From Baseline in Diastolic Blood Pressure at Each Study Visit	Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365	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.
Mean Change From Baseline in Overall Average Endothelial Cell Density at Day 365	Baseline (Day 1 pretreatment), Day 365	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.
Percentage of Subjects With 10 Percent or More Decrease From Baseline in Overall Average Endothelial Cell Density at Study Exit	Baseline (Day 1 pretreatment), Study Exit (Day 365, early termination visit, or unscheduled 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.
Mean Change From Baseline in Hematology by Visit - Basophil Level	Baseline (Day 1 pretreatment), Day 180, Day 365	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.
Mean Change From Baseline in Hematology by Visit - Basophils to Leukocytes Ratio Reported in Percentage of Cells	Baseline (Day 1 pretreatment), Day 180, Day 365	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.
Mean Change From Baseline in Hematology by Visit - Eosinophil Level	Baseline (Day 1 pretreatment), Day 180, Day 365	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.
Mean Change From Baseline in Hematology by Visit - Eosinophils to Leukocytes Ratio Reported in Percentage of Cells	Baseline (Day 1 pretreatment), Day 180, Day 365	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.
Mean Change From Baseline in Hematology by Visit - Erythrocyte Mean Corpuscular Hemoglobin Concentration Level	Baseline (Day 1 pretreatment), Day 180, Day 365	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.
Mean Change From Baseline in Hematology by Visit - Erythrocyte Mean Corpuscular Hemoglobin Level	Baseline (Day 1 pretreatment), Day 180, Day 365	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.
Mean Change From Baseline in Hematology by Visit - Erythrocyte Mean Corpuscular Volume	Baseline (Day 1 pretreatment), Day 180, Day 365	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.
Mean Change From Baseline in Hematology by Visit - Erythrocyte Level	Baseline (Day 1 pretreatment), Day 180, Day 365	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.
Mean Change From Baseline in Hematology by Visit - Erythrocyte Distribution Width Reported as Percentage of Variation of Cells	Baseline (Day 1 pretreatment), Day 180, Day 365	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.
Mean Change From Baseline in Hematology by Visit - Hematocrit Level	Baseline (Day 1 pretreatment), Day 180, Day 365	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.
Mean Change From Baseline in Hematology by Visit - Hemoglobin Level	Baseline (Day 1 pretreatment), Day 180, Day 365	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.
Mean Change From Baseline in Hematology by Visit - Leukocyte Level	Baseline (Day 1 pretreatment), Day 180, Day 365	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.
Mean Change From Baseline in Hematology by Visit - Lymphocyte Level	Baseline (Day 1 pretreatment), Day 180, Day 365	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.
Mean Change From Baseline in Hematology by Visit - Lymphocytes to Leukocytes Ratio Reported in Percentage of Cells	Baseline (Day 1 pretreatment), Day 180, Day 365	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.
Mean Change From Baseline in Hematology by Visit - Monocyte Level	Baseline (Day 1 pretreatment), Day 180, Day 365	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.
Mean Change From Baseline in Hematology by Visit - Monocytes to Leukocytes Ratio Reported in Percentage of Cells	Baseline (Day 1 pretreatment), Day 180, Day 365	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.
Mean Change From Baseline in Hematology by Visit - Neutrophil Level	Baseline (Day 1 pretreatment), Day 180, Day 365	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.
Mean Change From Baseline in Hematology by Visit - Neutrophils to Leukocytes Ratio Reported in Percentage of Cells	Baseline (Day 1 pretreatment), Day 180, Day 365	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.
Mean Change From Baseline in Hematology by Visit - Platelet Level	Baseline (Day 1 pretreatment), Day 180, Day 365	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.
Mean Change From Baseline in Hematology by Visit - Mean Platelet Volume	Baseline (Day 1 pretreatment), Day 180, Day 365	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.
Mean Change From Baseline in Chemistry by Visit - Alanine Aminotransferase Level	Baseline (Day 1 pretreatment), Day 180, Day 365	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.
Mean Change From Baseline in Chemistry by Visit - Albumin Level	Baseline (Day 1 pretreatment), Day 180, Day 365	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.
Mean Change From Baseline in Chemistry by Visit - Alkaline Phosphatase Level	Baseline (Day 1 pretreatment), Day 180, Day 365	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.
Mean Change From Baseline in Chemistry by Visit - Aspartate Aminotransferase Level	Baseline (Day 1 pretreatment), Day 180, Day 365	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.
Mean Change From Baseline in Chemistry by Visit - Calcium Level	Baseline (Day 1 pretreatment), Day 180, Day 365	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.
Mean Change From Baseline in Chemistry by Visit - Creatinine Level	Baseline (Day 1 pretreatment), Day 180, Day 365	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.
Mean Change From Baseline in Chemistry by Visit - Globulin Level	Baseline (Day 1 pretreatment), Day 180, Day 365	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.
Mean Change From Baseline in Chemistry by Visit - Potassium Level	Baseline (Day 1 pretreatment), Day 180, Day 365	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.
Mean Change From Baseline in Chemistry by Visit - Protein Level	Baseline (Day 1 pretreatment), Day 180, Day 365	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.
Mean Change From Baseline in Chemistry by Visit - Sodium Level	Baseline (Day 1 pretreatment), Day 180, Day 365	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.
Mean Change From Baseline in Chemistry by Visit - Triglyceride Level	Baseline (Day 1 pretreatment), Day 180, Day 365	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.
Mean Change From Baseline in Chemistry by Visit - Urea Nitrogen Level	Baseline (Day 1 pretreatment), Day 180, Day 365	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.
Mean Change From Baseline in Urinalysis by Visit - Specific Gravity Level	Baseline (Day 1 pretreatment), Day 180, Day 365	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.
Mean Change From Baseline in Urinalysis by Visit - pH Level	Baseline (Day 1 pretreatment), Day 180, Day 365	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.
Mean Best Corrected Visual Acuity (BCVA) Letter Score by Visit	Baseline (Day 1 pretreatment), Day 365	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.
Mean Corrected Visual Acuity in LogMar by Visit	Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365	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.
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Lid Erythema	Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365	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.
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Lid Edema	Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365	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.
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Conjunctiva Hyperemia	Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365	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.
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Conjunctiva Edema	Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365	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.
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Cornea Staining/Erosion	Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365	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.
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Cornea Edema	Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365	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.
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Anterior Chamber Cells	Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365	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.
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Anterior Chamber Flare	Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365	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.
Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Lens Opacity	Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365	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.
Mean Total Ocular Staining Score by Visit	Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365	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).
Mean Intraocular Pressure by Visit	Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365	Intraocular pressure was measured using Goldmann applanation tonometry and measured in millimeters mercury (mmHg). Values between 10mmHg and 20mmHg are considered normal eye pressure.
Number of Subjects With Clinically Significant Change From Baseline in Dilated Fundus Exam Results by Visit - Vitreous	Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365	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.
Number of Subjects With Clinically Significant Change From Baseline in Dilated Fundus Exam Results by Visit - Retina	Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365	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.
Number of Subjects With Clinically Significant Change From Baseline in Dilated Fundus Exam Results by Visit - Macula	Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365	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.
Number of Subjects With Clinically Significant Change From Baseline in Dilated Fundus Exam Results by Visit - Optic Nerve	Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365	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.
Number of Subjects With Clinically Significant Change From Baseline in Dilated Fundus Exam Results by Visit - Choroid	Baseline (Day 1 pretreatment), Day 14, Day 90, Day 180, Day 270, Day 365	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.

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (10): Arizona Eye Institute
🇺🇸
Sun City, Arizona, United States
Arizona Eye Center
🇺🇸
Chandler, Arizona, United States
Global Research Management
🇺🇸
Glendale, California, United States
Macy Eye Center
🇺🇸
Los Angeles, California, United States
Eye Research Foundation
🇺🇸
Newport Beach, California, United States
Shultz Vision
🇺🇸
Northridge, California, United States
SightMD
🇺🇸
Manhasset, New York, United States
University Eye Specialists
🇺🇸
Maryville, Tennessee, United States
Piedmont Eye Center
🇺🇸
Lynchburg, Virginia, United States
Periman Eye Institute
🇺🇸
Seattle, Washington, United States
Arizona Eye Institute
🇺🇸Sun City, Arizona, United States