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).

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.

• Authors: Jason Bacharach, Harvey B Dubiner, Brian Levy, Casey C Kopczynski, Gary D Novack, AR-13324-CS202 Study Group
• Journal: Ophthalmology (Ophthalmology) Vol. 122 Issue 2 Pg. 302-7 (Feb 2015) ISSN: 1549-4713 [Electronic] United States
• PMID: 25270273 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Chemical References

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

Topics

• Administration, Topical
• Adult
• Aged
• Aged, 80 and over
• Antihypertensive Agents (adverse effects, therapeutic use)
• Benzoates (adverse effects, 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, therapeutic use)
• Prostaglandins F, Synthetic (adverse effects, therapeutic use)
• Tonometry, Ocular
• Young Adult
• beta-Alanine (adverse effects, analogs & derivatives, therapeutic use)
• rho-Associated Kinases (antagonists & inhibitors)