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R. D. Williams, G. D. Novack, T. van Haarlem, C. Kopczynski, AR-12286 Phase 2a Study Group; Ocular Hypotensive Efficacy and Safety of the Rho Kinase Inhibitor AR-12286 in Patients With Elevated Intraocular Pressure. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1633. doi: https://doi.org/.
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To evaluate the ocular hypotensive efficacy and safety of 0.05%, 0.1% and 0.25% AR-12286 Ophthalmic Solutions in patients diagnosed with ocular hypertension or glaucoma. AR-12286 is a highly selective Rho kinase inhibitor designed to lower intraocular pressure by improving trabecular outflow.
Parallel comparison, vehicle-controlled, double-masked, 3-week randomized clinical trial. Subjects (n=89) with elevated intraocular pressure (IOP) were randomly assigned to receive either one of three concentrations of AR-12286 or its vehicle. Dosing was q.d. AM x 7 days, then q.d. PM x 7 days, then b.i.d. x 7 days. Primary and secondary efficacy endpoints 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 three 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 three concentrations. The largest IOP reductions were produced by 0.25% AR-12286 after b.i.d. dosing (up to -6.8 mm Hg; 28%). The 0.25% concentration had a long duration of effect, with q.d. PM dosing producing 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 q.d. PM dosing, hyperemia was seen in less than 10% of patients.
AR-12286 provided clinically and statistically significant ocular hypotensive efficacy in patients with ocular hypertension and glaucoma. The only safety finding of note was a transient, self-resolving ocular hyperemia. The top of the dose response for AR-12286 was not established; higher doses could provide greater efficacy, especially when administered q.d. PM.
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