Double-masked, randomized, dose-response study of AR-13324 versus latanoprost in patients with elevated intraocular pressure

Ophthalmology. 2015 Feb;122(2):302-7. doi: 10.1016/j.ophtha.2014.08.022. Epub 2014 Sep 27.

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).

Design: Double-masked, randomized study in 22 private practice ophthalmology clinics.

Participants: 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.

Main outcome measures: 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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Adult
  • Aged
  • Aged, 80 and over
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / therapeutic use*
  • Benzoates / adverse effects
  • Benzoates / therapeutic use*
  • Double-Blind Method
  • Female
  • Glaucoma, Open-Angle / drug therapy*
  • Humans
  • Intraocular Pressure / drug effects*
  • Latanoprost
  • Male
  • Middle Aged
  • Norepinephrine Plasma Membrane Transport Proteins / antagonists & inhibitors*
  • Ocular Hypertension / drug therapy
  • Ophthalmic Solutions / adverse effects
  • Ophthalmic Solutions / therapeutic use*
  • Prostaglandins F, Synthetic / adverse effects
  • Prostaglandins F, Synthetic / therapeutic use*
  • Tonometry, Ocular
  • Young Adult
  • beta-Alanine / adverse effects
  • beta-Alanine / analogs & derivatives*
  • beta-Alanine / therapeutic use
  • rho-Associated Kinases / antagonists & inhibitors*

Substances

  • Antihypertensive Agents
  • Benzoates
  • Norepinephrine Plasma Membrane Transport Proteins
  • Ophthalmic Solutions
  • Prostaglandins F, Synthetic
  • beta-Alanine
  • Latanoprost
  • rho-Associated Kinases
  • netarsudil