title: Double-masked, randomized, dose-response study of AR-13324 versus latanoprost in patients with elevated intraocular pressure.
abstract: OBJECTIVE
  AR-13324 is a small-molecule inhibitor of Rho kinase and a norepinephrine transporter. The objective of this 28-day study was to evaluate the ocular hypotensive efficacy and safety of AR-13324 ophthalmic solution compared with a positive control, latanoprost ophthalmic solution, in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT).
  
  
  METHODS
  Double-masked, randomized study in 22 private practice ophthalmology clinics.
  
  
  METHODS
  Participants were required to be adults with a diagnosis of OAG or OHT with unmedicated intraocular pressure (IOP) in the range of 22 to 36 mmHg.
  
  
  METHODS
  Patients were randomized to receive AR-13324 ophthalmic solution 0.01%, daily (pm), AR-13324 ophthalmic solution 0.02% daily (pm), or latanoprost 0.005% daily (pm) for 28 days.
  
  
  METHODS
  The primary efficacy endpoint was the mean diurnal IOP across subjects within the treatment group at day 28.
  
  
  RESULTS
  Randomized and treated were 224 patients, 213 (95.1%) of whom completed the study. On day 28, mean diurnal IOP was 20.1, 20.0, and 18.7 mmHg in the AR-13324 0.01%, 0.02%, and latanoprost groups, respectively, representing a decrease from unmedicated baseline of 5.5, 5.7, and 6.8 mmHg (P<0.001). The 5.7-mmHg reduction in IOP by AR-13324 0.02% did not meet the criterion for noninferiority to latanoprost. The most frequently reported adverse event was conjunctival/ocular hyperemia, with a combined incidence of 52%, 57%, and 16%, respectively. On day 28 at 08:00 hours, the incidence of mild to moderate hyperemia by biomicroscopy was 18%, 24%, and 11%, respectively.
  
  
  CONCLUSIONS
  AR-13324 0.02% was less effective than latanoprost by approximately 1 mmHg in patients with unmedicated IOPs of 22 to 35 mmHg. The major safety finding was ocular hyperemia, which was more common for both concentrations of AR-13324 than for latanoprost.
authors.affiliation: North Bay Eye Associates, Sonoma County, California.
authors.forename: Jason
authors.initials: J
authors.lastname: Bacharach
authors.affiliation: Clayton Eye Center, Morrow, Georgia.
authors.forename: Harvey B
authors.initials: HB
authors.lastname: Dubiner
authors.affiliation: Aerie Pharmaceuticals, Inc., Bedminster, New Jersey, and Research Triangle Park, North Carolina.
authors.forename: Brian
authors.initials: B
authors.lastname: Levy
authors.affiliation: Aerie Pharmaceuticals, Inc., Bedminster, New Jersey, and Research Triangle Park, North Carolina.
authors.forename: Casey C
authors.initials: CC
authors.lastname: Kopczynski
authors.affiliation: PharmaLogic Development, Inc, San Rafael, California. Electronic address: gary_novack@pharmalogic.com.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Novack
mesh_terms: D000287:Administration, Topical; 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*; D004311:Double-Blind Method; 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 / Q000009:adverse effects / Q000627:therapeutic use*; D011461:Prostaglandins F, Synthetic / Q000009:adverse effects / Q000627:therapeutic use*; D014065:Tonometry, Ocular; D055815:Young Adult; 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; D050484:Norepinephrine Plasma Membrane Transport Proteins; D009883:Ophthalmic Solutions; D011461:Prostaglandins F, Synthetic; D015091:beta-Alanine; D000077338:Latanoprost; D054460:rho-Associated Kinases; C000603944:netarsudil