Double-masked, Randomized, Dose-Response Study of AR-13324 versus Latanoprost in Patients with Elevated Intraocular Pressure

Objective: AR-13324 is a small-molecule inhibitor of Rho kinase and a norepinephrine transporter. The objective of this 28-day study was to evaluate the ocular hypotensive efficacy and safety of AR-13324 ophthalmic solution compared with a positive control, latanoprost ophthalmic solution, in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). Design: Double-masked, randomized study in 22 private practice ophthalmology clinics. Participants: Participants were required to be adults with a diagnosis of OAG or OHT with unmedicated intraocular pressure (IOP) in the range of 22 to 36 mmHg. Methods: Patients were randomized to receive AR-13324 ophthalmic solution 0.01%, daily (PM), AR-13324 ophthalmic solution 0.02% daily (PM), or latanoprost 0.005% daily (PM) for 28 days. Main Outcome Measures: The primary efficacy endpoint was the mean diurnal IOP across subjects within the treatment group at day 28. Results: Randomized and treated were 224 patients, 213 (95.1%) of whom completed the study. On day 28, mean diurnal IOP was 20.1, 20.0, and 18.7 mmHg in the AR-13324 0.01%, 0.02%, and latanoprost groups, respectively, representing a decrease from unmedicated baseline of 5.5, 5.7, and 6.8 mmHg (P<0.001). The 5.7-mmHg reduction in IOP by AR-13324 0.02% did not meet the criterion for noninferiority to latanoprost. The most frequently reported adverse event was conjunctival/ocular hyperemia, with a combined incidence of 52%, 57%, and 16%, respectively. On day 28 at 08: 00 hours, the incidence of mild to moderate hyperemia by biomicroscopy was 18%, 24%, and 11%, respectively. Conclusions: AR-13324 0.02% was less effective than latanoprost by approximately 1 mmHg in patients with unmedicated IOPs of 22 to 35 mmHg. The major safety finding was ocular hyperemia, which was more common for both concentrations of AR-13324 than for latanoprost. (C) 2015 by the American Academy of Ophthalmology.