title: Phase 1 clinical trials of a selective Rho kinase inhibitor, K-115.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Randomized, placebo-controlled, double-masked, group comparison phase 1 clinical trial.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  K-115 is a promising drug for lowering IOP in healthy adult eyes, with tolerable adverse events during at least short-term administration.
authors.affiliation: Department of Ophthalmology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
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: D000287:Administration, Topical; D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects*; D007546:Isoquinolines / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D009883:Ophthalmic Solutions; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects; D014065:Tonometry, Ocular; D014792:Visual Acuity; D055815:Young Adult; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000959:Antihypertensive Agents; D007546:Isoquinolines; C584679:K-115; D009883:Ophthalmic Solutions; D013449:Sulfonamides; D054460:rho-Associated Kinases