A Long-Term Safety Study Evaluating the Safety and Systemic Exposure of AR-15512 (COMET-4)

A Long-Term Safety Study Evaluating the Safety and Systemic Exposure of AR-15512, a Cold Thermoreceptor Modulator, for the Treatment of Dry Eye Disease (COMET-4)

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.

Study Overview

• Status: Completed
• Conditions: Dry Eye Disease
• Intervention / Treatment: Drug: AR-15512 vehicle ophthalmic solution; Drug: 0.003% AR-15512 ophthalmic solution

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.

• Study Type: Interventional
• Enrollment (Actual): 275
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Chandler, Arizona, United States, 85225
      • Arizona Eye Center
    • Sun City, Arizona, United States, 85351
      • Arizona Eye Institute
  • California
    • Glendale, California, United States, 91204
      • Global Research Management
    • Los Angeles, California, United States, 90048
      • Macy Eye Center
    • Newport Beach, California, United States, 92663
      • Eye Research Foundation
    • Northridge, California, United States, 91325
      • Shultz Vision
  • New York
    • Manhasset, New York, United States, 11030
      • SightMD
  • Tennessee
    • Maryville, Tennessee, United States, 37803
      • University Eye Specialists
  • Virginia
    • Lynchburg, Virginia, United States, 24502
      • Piedmont Eye Center
  • Washington
    • Seattle, Washington, United States, 98119
      • Periman Eye Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 0.003% AR-15512; 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days	Drug: 0.003% AR-15512 ophthalmic solution; Active ingredients administered via topical ocular instillation
Placebo Comparator: AR-15512 Vehicle; AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days	Drug: AR-15512 vehicle ophthalmic solution; Inactive ingredients administered via topical ocular instillation

What is the study measuring?

Primary Outcome Measures

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minimum Plasma Concentration (Cmin)	From the blood samples collected from each subject, the minimum amount of AR-15512, the test drug, that may be present in the blood will be measured at a laboratory. Each measure will be recorded in pg/ml. Lower numbers represent better outcome.	Day 1, 14 and 90
Accumulation Ratio (Rcmax)	From the blood samples collected from each subject, the amount of AR-15512, the test drug, that may have accumulated in the blood will be measured in a laboratory. Each measure will be recorded as a number based on a ratio (e.g. Cmax Day 90 / Cmax Day 1). Lower numbers represent better outcome.	Day 1, 14 and 90
Time to Maximum Concentration (Tmax)	From the blood samples collected from each subject, the time at which the highest amount of AR-15512, the test drug, is measured in the blood will be measured in a laboratory. Each measure will be recorded in hours/min/sec.	Day 1, 14 and 90
Time to Last Detectable Concentration (Tlast)	From the blood samples collected from each subject, the time at which the last detectable amount of AR-15512, the test drug, is measured in the blood will be measured in a laboratory. Each measure will be recorded in hours/min/sec. Lower number represents better outcome.	Day 1, 14 and 90
Total Exposure (AUC0-last)	From the blood samples collected from each subject, the overall amount of AR-15512, the test drug, in the blood from the start of dose administration to the time after dosing at which the last quantifiable concentration was observed will be measured in a laboratory. Each measure will be recorded in µg*h/L. Lower numbers represent better outcome.	Day 1, 14 and 90

Collaborators and Investigators

• Sponsor: Aerie Pharmaceuticals
• Investigators: Study Director: Scientific Advisor, CRD, Alcon Research, LLC

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2022
• Primary Completion (Actual): February 28, 2024
• Study Completion (Actual): February 28, 2024

Study Registration Dates

• First Submitted: July 26, 2022
• First Submitted That Met QC Criteria: August 5, 2022
• First Posted (Actual): August 9, 2022

Study Record Updates

• Last Update Posted (Actual): August 13, 2025
• Last Update Submitted That Met QC Criteria: July 23, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Corneal Diseases; Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Eye Diseases; Dry Eye Syndromes; Keratoconjunctivitis Sicca; Pharmaceutical Solutions; Pharmaceutical Solutions; Ophthalmic Solutions
• Other Study ID Numbers: AR-15512-LTSS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No