title: Phase 2 randomized clinical study of a Rho kinase inhibitor, K-115, in primary open-angle glaucoma and ocular hypertension.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Ophthalmology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan. Electronic address: tanihara@pearl.ocn.ne.jp.
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Tanihara
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Inoue
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Kuwayama
authors.forename: Haruki
authors.initials: H
authors.lastname: Abe
authors.forename: Makoto
authors.initials: M
authors.lastname: Araie
mesh_terms: D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005902:Glaucoma, Open-Angle / Q000188:drug therapy*; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects*; D007546:Isoquinolines / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009798:Ocular Hypertension / Q000188:drug therapy; D011446:Prospective Studies; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects; D014065:Tonometry, Ocular; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D007546:Isoquinolines; C584679:K-115; D013449:Sulfonamides; D054460:rho-Associated Kinases