title: Intraocular pressure-lowering effects and safety of topical administration of a selective ROCK inhibitor, SNJ-1656, in healthy volunteers.
abstract: OBJECTIVE
  To investigate the effects and safety of topical administration of an ophthalmic solution of a selective Rho-associated coiled coil-forming protein kinase (ROCK) inhibitor, SNJ-1656, 0.003% to 0.1%, in healthy male adult volunteers.
  
  
  METHODS
  Randomized, double-masked, group-comparison, phase 1 clinical study. In the initial single-instillation trial, 45 healthy volunteers were randomly subdivided into 5 groups and treated with SNJ-1656 in concentrations of 0.003%, 0.01%, 0.03%, 0.05%, and 0.1% in stepwise fashion. In the repeated-instillation trial, 36 healthy volunteers were assigned to receive SNJ-1656 ophthalmic solution at the following concentrations and dosages: 0.05% once daily, 0.1% once daily, 0.05% twice daily, or 0.1% twice daily. In our studies, the administration of the solution and subsequent examinations (including intraocular pressure [IOP] measurements) were performed in a double-masked fashion.
  
  
  RESULTS
  After single instillation of placebo or SNJ-1656, in concentrations of 0.003%, 0.01%, 0.03%, 0.05%, and 0.1%, the changes in IOP from the baseline were -0.91, -1.18, -1.48, - 2.20 (P = .04 vs placebo), -1.48, and -1.98 mm Hg, respectively, at 2 hours, and -0.63,-0.95, -1.79, -2.26 (P = .01 vs placebo), -1.95, and -3.00 mm Hg (P < .001 vs placebo) respectively, at 4 hours. Significant IOP reductions after repeated instillation were also found. On slitlamp examination during the trial, there were no significant adverse findings except hyperemia of the bulbar and palpebral conjunctiva after instillation.
  
  
  CONCLUSIONS
  This clinical study demonstrated that SNJ-1656 is a safe topical agent effective in reducing IOP in human eyes.
authors.affiliation: Department of Ophthalmology and Visual Science, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan. tanihara@pearl.ocn.ne.jp
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Tanihara
authors.forename: Masaru
authors.initials: M
authors.lastname: Inatani
authors.forename: Megumi
authors.initials: M
authors.lastname: Honjo
authors.forename: Hideki
authors.initials: H
authors.lastname: Tokushige
authors.forename: Junichi
authors.initials: J
authors.lastname: Azuma
authors.forename: Makoto
authors.initials: M
authors.lastname: Araie
mesh_terms: D000287:Administration, Topical; D000328:Adult; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D009883:Ophthalmic Solutions / Q000008:administration & dosage* / Q000009:adverse effects; D014065:Tonometry, Ocular; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D009883:Ophthalmic Solutions; D054460:rho-Associated Kinases