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

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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.

Section snippets

Methods

A multicenter, prospective, randomized, placebo-controlled, double-masked, parallel-group comparison clinical study was conducted at 29 clinical centers in Japan. The institutional review board review was prospective and the study protocol was approved by each institutional review board (Appendix, Supplemental Material). Candidate patients for the clinical trial received complete information regarding the protocol, and written informed consent was obtained from each participant before entry to

Results

The enrollment of patients began in February 2010 and was completed in May 2010. In this phase 2 clinical trial, 232 patients with POAG or OHT were enrolled and 210 patients who fulfilled the eligibility criteria were subdivided randomly into 4 groups: 54 patients were assigned to placebo, 53 were assigned to 0.1% K-115, 54 were assigned to 0.2% K-115, and 49 were assigned to 0.4% K-115 and were subjected to the analyses on safety. A total of 7 patients were excluded from analyses because of

Discussion

In this clinical trial for the novel rho kinase inhibitor K-115, there was a dose-dependent reduction in the adjusted mean of the change in IOP. Most notably, the 0.4% concentration significantly and steadily reduced IOP in comparison with placebo in patients with POAG or OHT at each time point of the last visit. During 8 weeks of K-115 administration, a dose-dependent significant IOP reduction was found in a steady and repeated manner. Because 0.4% K-115 showed the most suitable IOP reduction,

Hidenobu Tanihara, MD, is a Professor and Chairman at the Department of Ophthalmology, Faculty of Life Science, Kumamoto University, Japan. His research interests include aqueous outflow system, molecular mechanisms related to glaucomatous optic neuropathy, neuro-protection and -regeneration, glaucoma surgery, and secondary glaucoma; and he has published more than 200 papers to peer-reviewed articles in these areas.

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Hidenobu Tanihara, MD, is a Professor and Chairman at the Department of Ophthalmology, Faculty of Life Science, Kumamoto University, Japan. His research interests include aqueous outflow system, molecular mechanisms related to glaucomatous optic neuropathy, neuro-protection and -regeneration, glaucoma surgery, and secondary glaucoma; and he has published more than 200 papers to peer-reviewed articles in these areas.

Supplemental Material available AJO.com.

Haruki Abe is now affiliated with the Niigata Eye Clinic, Niigata, Japan.

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