title: Ocular hypotensive effect of the Rho kinase inhibitor AR-12286 in patients with glaucoma and ocular hypertension.
abstract: OBJECTIVE
  To evaluate the ocular hypotensive efficacy of 0.05%, 0.1% and 0.25% AR-12286 Ophthalmic Solutions in patients diagnosed with ocular hypertension or glaucoma.
  
  
  METHODS
  Parallel comparison, vehicle-controlled, double-masked, 3-week randomized clinical trial.
  
  
  METHODS
  Subjects (n = 89) with elevated intraocular pressure (IOP) were assigned randomly to receive either 1 of 3 concentrations of AR-12286 or its vehicle. Dosing was once-daily in the morning for 7 days, then once-daily in the evening for 7 days, then twice daily for 7 days. Primary and secondary efficacy end points were mean IOP at each diurnal time point (8 am, 10 am, 12 pm, and 4 pm) and mean change in IOP from baseline, respectively.
  
  
  RESULTS
  All 3 concentrations of AR-12286 produced statistically and clinically significant reductions in mean IOP that were dose dependent, with peak effects occurring 2 to 4 hours after dosing. Mean IOP at peak effect ranged from 17.6 to 18.7 mm Hg (-6.8 to -4.4 mm Hg) for the 3 concentrations. The largest IOP reductions were produced by 0.25% AR-12286 after twice daily dosing (up to -6.8 mm Hg; 28%). The 0.25% concentration dosed once-daily in the evening produced highly significant IOP reductions throughout the following day (-5.4 to -4.2 mm Hg). The only adverse event of note was trace (+0.5) to moderate (+2) conjunctival hyperemia that was transient, typically lasting 4 hours or less. After once-daily evening dosing, hyperemia was seen in less than 10% of patients.
  
  
  CONCLUSIONS
  AR-12286 was well tolerated and provided clinically and statistically significant ocular hypotensive efficacy in patients with ocular hypertension and glaucoma.
authors.affiliation: Taustine Eye Center, Louisville, Kentucky, USA.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Williams
authors.forename: Gary D
authors.initials: GD
authors.lastname: Novack
authors.forename: Thomas
authors.initials: T
authors.lastname: van Haarlem
authors.forename: Casey
authors.initials: C
authors.lastname: Kopczynski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005902:Glaucoma, Open-Angle / Q000188:drug therapy*; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D007546:Isoquinolines / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009798:Ocular Hypertension / Q000188:drug therapy; D009883:Ophthalmic Solutions / Q000009:adverse effects / Q000627:therapeutic use*; D014065:Tonometry, Ocular; D016896:Treatment Outcome; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: C581711:AR-12286; D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D009883:Ophthalmic Solutions; D054460:rho-Associated Kinases