Phase 2 Randomized Clinical Study of a Rho Kinase Inhibitor, K-115, in Primary Open-Angle Glaucoma and Ocular Hypertension

PURPOSE: To identify the optimal dose of a novel Rho kinase inhibitor, K-115, by assessing dose dependency of the intraocular pressure (IOP)-lowering effects and the safety in patients with primary open-angle glaucoma or ocular hypertension. DESIGNS: Multicenter, prospective, randomized, placebo-controlled, double-masked, parallel group comparison clinical study. METHODS: After appropriate washout periods, 210 patients with primary open-angle glaucoma or ocular hypertension were subdivided into 4 groups and were treated with K-115 in concentrations of 0.1%, 0.2%, and 0.4% or placebo twice daily for 8 weeks. The dose response of TOP reduction and the incidence of adverse events by K-115 or placebo were investigated. RESULTS: The mean baseline TOP was between 23.0 and 23.4 mm Hg. The mean TOP reductions of the last visit from baseline were -2.2 mm Hg, -3.4 mm Hg, -3.2 mm Hg, and -3.5 mm Hg, respectively, in the placebo, 0.1%, 0.2%, and 0.4% groups at before instillation (9:00); -2.5 mm Hg, -3.7 mm Hg, -4.2 mm Hg, and -4.5 mm Hg at 2 hours after instillation (11:00); and -1.9 mm Hg, -3.2 mm Hg, -2.7 mm Hg, and -3.1 mm Hg at 8 hours after instillation (17:00). The dose-dependent TOP-lowering effect of K-115 was statistically significant at all time points. Also, conjunctival hyperemia was found in 7 (13.0%) of 54 patients for placebo, 23 (43.4%) of 53 patients for the 0.1% group, 31(57.4%) of 54 patients for the 0.2% group, and 32 (65.3%) of 49 patients for the 0.4% group. CONCLUSIONS: On the basis of this dose-response study, K-115 0.4% has been selected to be the optimal dose and has the potential to be a promising new agent for glaucoma to control 24-hour TOP by twice-daily dosing. ((C) 2013 by Elsevier Inc. All rights reserved.)