Phase 1 Clinical Trials of a Selective Rho Kinase Inhibitor, K-115

IMPORTANCE We conducted a series of phase 1 clinical trials to elucidate the efficacy and safety of the selective Rho kinase inhibitor K-115 as a candidate drug for the treatment of glaucoma. We report the intraocular pressure (IOP)–lowering effects and safety of K-115 based on our results. OBJECTIVE To study the IOP-lowering effects and safety of topical administration of a selective Rho kinase inhibitor, K-115, in healthy male adult volunteers. DESIGN AND SETTING Randomized, placebo-controlled, double-masked, group comparison phase 1 clinical trial. PARTICIPANTS In the initial single-instillation trial, 50 healthy volunteers were subdivided into groups and treated with placebo or K-115 in concentrations of 0.05%, 0.1%, 0.2%, 0.4%, and 0.8% in a stepwise manner. In the repeated-instillation trial, another 50 healthy volunteers were subdivided into groups and treated with placebo or K-115 in concentrations of 0.05%, 0.1%, 0.2%, 0.4%, and 0.8% twice daily for 7 days in a stepwise manner. MAIN OUTCOMES AND MEASURES In these clinical trials, the administration of eyedrops and associated examinations (including IOP measurements) were performed in a double-masked manner. RESULTS After single instillation of placebo or K-115 in concentrations of 0.05%, 0.1%, 0.2%, 0.4%, and 0.8%, the changes in IOP from baseline were −1.6 mm Hg for placebo and −3.4, −2.2, −2.6, −4.0, and −4.3 mm Hg, respectively, for the different concentrations 2 hours after instillation. Similar to the single-instillation trial, IOP reductions in the repeated-instillation trial were found after each instillation, with maximal reduction 1 to 2 hours after instillation. In the safety trial, slight to mild conjunctival hyperemia was found in more than half of the participants treated with K-115; it was found after each instillation and spontaneously resolved within 1½ hours. CONCLUSIONS AND RELEVANCE K-115 is a promising drug for lowering IOP in healthy adult eyes, with tolerable adverse events during at least short-term administration.