Ocular Hypotensive Effect of the Rho Kinase Inhibitor AR-12286 in Patients With Glaucoma and Ocular Hypertension

• Published in: American journal of ophthalmology Vol. 152; no. 5; pp. 834 - 841.e1
• Main Authors: Williams, Robert D., Novack, Gary D., van Haarlem, Thomas, Kopczynski, Casey
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.11.2011; Elsevier; Elsevier Limited
• Subjects: Adult; Aged; Aged, 80 and over; Antihypertensive Agents - adverse effects; Antihypertensive Agents - therapeutic use; Biological and medical sciences; Double-Blind Method; Enzyme Inhibitors - adverse effects; Enzyme Inhibitors - therapeutic use; Eyes & eyesight; Female; Glaucoma; Glaucoma and intraocular pressure; Glaucoma, Open-Angle - drug therapy; Humans; Intraocular Pressure - drug effects; Isoquinolines - adverse effects; Isoquinolines - therapeutic use; Male; Medical sciences; Middle Aged; Miscellaneous; Ocular Hypertension - drug therapy; Ophthalmic Solutions - adverse effects; Ophthalmic Solutions - therapeutic use; Ophthalmology; Proteins; rho-Associated Kinases - antagonists & inhibitors; Therapy; Tonometry, Ocular; Treatment Outcome; California; Glaucoma; Human; Protozoa; Ocular; Enzyme; Transferases; Ocular hypertension; Eye; Hypotensive drug; Eye disease; Glaucoma (eye); Kinase; Ciliata; Inhibitor; Ophthalmology
• ISSN: 0002-9394; 1879-1891; 1879-1891
• DOI: 10.1016/j.ajo.2011.04.012

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. Parallel comparison, vehicle-controlled, double-masked, 3-week randomized clinical trial. 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. 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. AR-12286 was well tolerated and provided clinically and statistically significant ocular hypotensive efficacy in patients with ocular hypertension and glaucoma.