Phase 3 N=275 Randomized Double-blind Treatment

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

Dry Eye Disease

Bottom Line

View on ClinicalTrials.gov: NCT05493111 ↗

Enrolled (actual)

275

Serious AEs

2.7%

Results posted

Aug 2025

Primary outcome: Primary: Ocular Treatment-Emergent Adverse Events by Preferred Term With Incidence Greater Than 2 Percent — 90; 7; 2; 3 adverse event

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: 0.003% AR-15512 ophthalmic solution (Drug); AR-15512 vehicle ophthalmic solution (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Aerie Pharmaceuticals
Primary completion: Feb 2024

Outcome Measures

Outcome	Result	p-value
PRIMARY Ocular Treatment-Emergent Adverse Events by Preferred Term With Incidence Greater Than 2 Percent	90; 7; 2; 3; 1; 2	—
PRIMARY Mean Change From Baseline in Heart Rate at Each Study Visit	0.7; 0.6; 1.4; 1.7; 0.5; -0.9	—
PRIMARY Mean Change From Baseline in Systolic Blood Pressure at Each Study Visit	1.4; 1.7; 0.0; 1.2; -3.3; 0.1	—
PRIMARY Mean Change From Baseline in Diastolic Blood Pressure at Each Study Visit	1.7; 0.6; 0.2; 1.1; 1.1; 1.6	—
PRIMARY Mean Change From Baseline in Overall Average Endothelial Cell Density at Day 365	12.8; 32.4; -40.4; -15.7	—
PRIMARY Percentage of Subjects With 10 Percent or More Decrease From Baseline in Overall Average Endothelial Cell Density at Study Exit	3.3; 2.6; 5.1; 2.5	—
PRIMARY Mean Change From Baseline in Hematology by Visit - Basophil Level	0.00; -0.01; -0.01; -0.01	—
PRIMARY Mean Change From Baseline in Hematology by Visit - Basophils to Leukocytes Ratio Reported in Percentage of Cells	0.03; 0.02; -0.05; -0.02	—
PRIMARY Mean Change From Baseline in Hematology by Visit - Eosinophil Level	0.02; 0.01; 0.02; 0.00	—
PRIMARY Mean Change From Baseline in Hematology by Visit - Eosinophils to Leukocytes Ratio Reported in Percentage of Cells	0.29; 0.20; 0.34; 0.13	—
PRIMARY Mean Change From Baseline in Hematology by Visit - Erythrocyte Mean Corpuscular Hemoglobin Concentration Level	-2.0; -1.3; 1.2; 0.9	—
PRIMARY Mean Change From Baseline in Hematology by Visit - Erythrocyte Mean Corpuscular Hemoglobin Level	-0.01; 0.01; 0.21; 0.26	—
PRIMARY Mean Change From Baseline in Hematology by Visit - Erythrocyte Mean Corpuscular Volume	0.53; 0.33; 0.28; 0.50	—
PRIMARY Mean Change From Baseline in Hematology by Visit - Erythrocyte Level	-0.071; -0.036; -0.073; -0.076	—
PRIMARY Mean Change From Baseline in Hematology by Visit - Erythrocyte Distribution Width Reported as Percentage of Variation of Cells	0.09; 0.13; -0.02; -0.17	—
PRIMARY Mean Change From Baseline in Hematology by Visit - Hematocrit Level	-0.0038; -0.0020; -0.0053; -0.0051	—
PRIMARY Mean Change From Baseline in Hematology by Visit - Hemoglobin Level	-2.1; -1.1; -1.3; -1.3	—
PRIMARY Mean Change From Baseline in Hematology by Visit - Leukocyte Level	-0.06; -0.46; -0.12; -0.38	—
PRIMARY Mean Change From Baseline in Hematology by Visit - Lymphocyte Level	-0.28; -0.28; -0.18; -0.32	—
PRIMARY Mean Change From Baseline in Hematology by Visit - Lymphocytes to Leukocytes Ratio Reported in Percentage of Cells	-3.21; -1.76; -1.95; -2.20	—
PRIMARY Mean Change From Baseline in Hematology by Visit - Monocyte Level	-0.02; -0.03; -0.01; -0.01	—
PRIMARY Mean Change From Baseline in Hematology by Visit - Monocytes to Leukocytes Ratio Reported in Percentage of Cells	-0.10; 0.21; 0.09; 0.25	—
PRIMARY Mean Change From Baseline in Hematology by Visit - Neutrophil Level	0.20; -0.17; 0.05; -0.05	—
PRIMARY Mean Change From Baseline in Hematology by Visit - Neutrophils to Leukocytes Ratio Reported in Percentage of Cells	3.00; 1.32; 1.58; 1.84	—
PRIMARY Mean Change From Baseline in Hematology by Visit - Platelet Level	-3.9; -9.0; -3.7; -1.5	—
PRIMARY Mean Change From Baseline in Hematology by Visit - Mean Platelet Volume	-0.24; -0.15; -0.04; -0.24	—
PRIMARY Mean Change From Baseline in Chemistry by Visit - Alanine Aminotransferase Level	0.3; -2.5; -0.2; -1.4	—
PRIMARY Mean Change From Baseline in Chemistry by Visit - Albumin Level	-2.0; -1.9; -2.1; -2.1	—
PRIMARY Mean Change From Baseline in Chemistry by Visit - Alkaline Phosphatase Level	2.5; 0.4; -1.3; -3.5	—
PRIMARY Mean Change From Baseline in Chemistry by Visit - Aspartate Aminotransferase Level	0.6; -0.1; 0.0; 0.1	—
PRIMARY Mean Change From Baseline in Chemistry by Visit - Calcium Level	-0.044; -0.037; -0.049; -0.055	—
PRIMARY Mean Change From Baseline in Chemistry by Visit - Creatinine Level	1.3; -0.2; 6.0; 1.3	—
PRIMARY Mean Change From Baseline in Chemistry by Visit - Globulin Level	0.3; 0.5; 0.0; -0.1	—
PRIMARY Mean Change From Baseline in Chemistry by Visit - Potassium Level	0.09; 0.11; 0.06; 0.16	—
PRIMARY Mean Change From Baseline in Chemistry by Visit - Protein Level	-1.7; -1.4; -2.1; -2.2	—
PRIMARY Mean Change From Baseline in Chemistry by Visit - Sodium Level	0.0; -0.1; 0.4; 0.5	—
PRIMARY Mean Change From Baseline in Chemistry by Visit - Triglyceride Level	0.079; -0.276; -0.024; -0.120	—
PRIMARY Mean Change From Baseline in Chemistry by Visit - Urea Nitrogen Level	0.22; 0.06; 0.16; 0.044	—
PRIMARY Mean Change From Baseline in Urinalysis by Visit - Specific Gravity Level	0.0005; 0.0020; 0.0007; 0.0019	—
PRIMARY Mean Change From Baseline in Urinalysis by Visit - pH Level	0.06; -0.02; 0.05; 0.03	—
PRIMARY Mean Best Corrected Visual Acuity (BCVA) Letter Score by Visit	84.9; 84.7; 85.8; 84.9; 85.1; 84.6	—
PRIMARY Mean Corrected Visual Acuity in LogMar by Visit	0.062; 0.061; 0.064; 0.080; 0.055; 0.053	—
PRIMARY Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Lid Erythema	1; 1; 0; 0; 0; 0	—
PRIMARY Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Lid Edema	0; 0; 0; 0; 0; 0	—
PRIMARY Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Conjunctiva Hyperemia	2; 2; 0; 0; 0; 0	—
PRIMARY Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Conjunctiva Edema	0; 0; 0; 0; 0; 0	—
PRIMARY Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Cornea Staining/Erosion	2; 2; 0; 0; 0; 0	—
PRIMARY Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Cornea Edema	0; 0; 0; 0; 0; 0	—
PRIMARY Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Anterior Chamber Cells	0; 0; 0; 0; 0; 0	—
PRIMARY Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Anterior Chamber Flare	0; 0; 0; 0; 0; 0	—
PRIMARY Number of Subjects With Clinically Significant Biomicroscopy Findings as Determined by the Investigator at Each Study Visit - Lens Opacity	0; 0; 0; 0; 0; 0	—
PRIMARY Mean Total Ocular Staining Score by Visit	4.08; 4.36; 3.77; 4.02; 3.46; 3.70	—
PRIMARY Mean Intraocular Pressure by Visit	15.4; 15.6; 15.5; 15.6; 15.5; 15.6	—
PRIMARY Number of Subjects With Clinically Significant Change From Baseline in Dilated Fundus Exam Results by Visit - Vitreous	0; 0; 0; 0; 0; 0	—
PRIMARY Number of Subjects With Clinically Significant Change From Baseline in Dilated Fundus Exam Results by Visit - Retina	0; 0; 0; 0; 0; 0	—
PRIMARY Number of Subjects With Clinically Significant Change From Baseline in Dilated Fundus Exam Results by Visit - Macula	0; 0; 0; 0; 0; 0	—
PRIMARY Number of Subjects With Clinically Significant Change From Baseline in Dilated Fundus Exam Results by Visit - Optic Nerve	0; 0; 0; 0; 0; 0	—
PRIMARY Number of Subjects With Clinically Significant Change From Baseline in Dilated Fundus Exam Results by Visit - Choroid	0; 0; 0; 0; 0; 0	—

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.

Eligibility Criteria

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.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT05493111). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.