title: Fixed-dose combination of AR-13324 and latanoprost: a double-masked, 28-day, randomised, controlled study in patients with open-angle glaucoma or ocular hypertension.
abstract: To evaluate the ocular hypotensive efficacy of fixed-dose combinations of the Rho kinase inhibitor and norepinephrine transport inhibitor AR-13324 (0.01% and 0.02%) and latanoprost (PG324 Ophthalmic Solution) relative to the active components AR-13324 0.02% and latanoprost 0.005%, used bilaterally at night.
  
  
  
  This was a double-masked, randomised, parallel comparison study in patients with open-angle glaucoma or ocular hypertension. After washout, patients were randomised to one of four treatment arms and treated for 28 days. The primary efficacy variable was mean diurnal intraocular pressure (IOP) at day 29.
  
  
  
  We randomised 298 patients, of whom 292 (98%) completed the study. Mean unmedicated diurnal IOPs (study eye) was 25.1, 25.1, 26.0 and 25.4 in the PG324 0.01%, PG324 0.02%, latanoprost and AR-13324 0.02% groups, respectively. On day 29, mean diurnal IOP decreased to 17.3, 16.5, 18.4 and 19.1 mm Hg, respectively. For the primary efficacy variable of mean diurnal IOP at day 29, PG324 0.02% met the criterion for statistical superiority relative to both latanoprost and AR-13324 0.02% (p<0.0001), providing additional IOP lowering of 1.9 and 2.6 mm Hg, respectively. PG324 0.01% also met the criterion for superiority. The most frequently reported adverse event was conjunctival hyperaemia with an incidence of 41% (30/73), 40% (29/73), 14% (10/73) and 40% (31/78) in the PG324 0.01%, PG324 0.02%, latanoprost and AR-13324 0.02% groups, respectively.
  
  
  
  In this short-term study, the fixed-dose combination of AR-13324 0.02% and latanoprost 0.005% in PG324 Ophthalmic Solution provides clinically and statistically superior ocular hypotensive efficacy relative to its individual active components at the same concentrations. The only safety finding of note was transient asymptomatic conjunctival hyperaemia which was typically of mild severity.
  
  
  
  NCT02057575.
authors.affiliation: Sacramento Eye Consultants, Sacramento, California, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lewis
authors.affiliation: Aerie Pharmaceuticals Inc., Bridgewater, Bridgewater, New Jersey, USA/Research Triangle Park, North Carolina, USA SDC Inc., Tempe, Arizona, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Levy
authors.affiliation: Aerie Pharmaceuticals Inc., Bridgewater, Bridgewater, New Jersey, USA/Research Triangle Park, North Carolina, USA SDC Inc., Tempe, Arizona, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Ramirez
authors.affiliation: Aerie Pharmaceuticals Inc., Bridgewater, Bridgewater, New Jersey, USA/Research Triangle Park, North Carolina, USA SDC Inc., Tempe, Arizona, USA.
authors.forename: Casey C
authors.initials: CC
authors.lastname: Kopczynski
authors.affiliation: SDC Inc., Tempe, Arizona, USA.
authors.forename: Dale W
authors.initials: DW
authors.lastname: Usner
authors.affiliation: PharmaLogic Development Inc., San Rafael, California, USA.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Novack
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001565:Benzoates / Q000009:adverse effects / Q000627:therapeutic use*; D063171:Corneal Pachymetry; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D005902:Glaucoma, Open-Angle / Q000188:drug therapy*; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D000077338:Latanoprost; D008297:Male; D008875:Middle Aged; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D009798:Ocular Hypertension / Q000188:drug therapy; D009883:Ophthalmic Solutions; D011461:Prostaglandins F, Synthetic / Q000009:adverse effects / Q000627:therapeutic use*; D014065:Tonometry, Ocular; D015091:beta-Alanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000959:Antihypertensive Agents; D001565:Benzoates; D004338:Drug Combinations; D050484:Norepinephrine Plasma Membrane Transport Proteins; D009883:Ophthalmic Solutions; D011461:Prostaglandins F, Synthetic; D015091:beta-Alanine; D000077338:Latanoprost; D054460:rho-Associated Kinases; C000603944:netarsudil
keywords: Glaucoma; Intraocular pressure