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

• Published in: American journal of ophthalmology Vol. 156; no. 4; pp. 731 - 736.e2
• Main Authors: Tanihara, Hidenobu, Inoue, Toshihiro, Yamamoto, Tetsuya, Kuwayama, Yasuaki, Abe, Haruki, Araie, Makoto
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2013; Elsevier Limited
• Subjects: Antihypertensive Agents - administration & dosage; Antihypertensive Agents - adverse effects; Cataracts; Clinical trials; Dose-Response Relationship, Drug; Double-Blind Method; Drug dosages; Enzyme Inhibitors - administration & dosage; Enzyme Inhibitors - adverse effects; Female; Glaucoma; Glaucoma, Open-Angle - drug therapy; Humans; Hypertension; Intraocular Pressure - drug effects; Isoquinolines - administration & dosage; Isoquinolines - adverse effects; Male; Middle Aged; Ocular Hypertension - drug therapy; Ophthalmology; Patients; Prospective Studies; Review boards; rho-Associated Kinases - antagonists & inhibitors; Standard deviation; Sulfonamides - administration & dosage; Sulfonamides - adverse effects; Surgery; Therapy; Tonometry, Ocular
• ISSN: 0002-9394; 1879-1891
• DOI: 10.1016/j.ajo.2013.05.016

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 IOP reduction and the incidence of adverse events by K-115 or placebo were investigated. Results The mean baseline IOP was between 23.0 and 23.4 mm Hg. The mean IOP 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 IOP-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 IOP by twice-daily dosing.