Varying concentrations of ROCK inhibitor may reduce IOP

Am J Ophthalmol. 2011;152(5):834-841

ROCK inhibitor AR-12286 may provide ocular hypotensive efficacy in patients with ocular hypertension and glaucoma, according to a phase 2a study.

Eighty-nine patients with elevated IOP were randomly assigned to receive one of three concentrations (0.05%, 0.1% or 0.25%) of AR-12286 (Aerie Pharmaceuticals) or placebo. Dosing occurred once daily in the morning for 7 days, once daily in the evening for 7 days and then twice daily for 7 days.

The parallel-comparison, vehicle-controlled, double-masked study - the first in-human analysis assessing AR-12286 — found all three concentrations to produce statistically significant pressure reductions. Reductions were dose-dependent, with peak effects occurring 2 hours to 4 hours after dosing. The largest decreases, up to 28%, occurred in patients who received 0.25% AR-12286 twice daily.

The only notable complication was trace to moderate conjunctival hyperemia that generally lasted no more than 4 hours. After once-daily evening dosing, hyperemia occurred in less than 10% of patients.

Given the study's design, it was not possible to discern a relationship between duration of treatment and incidence or severity of hyperemia, the authors said. Moreover, the top dose curve remained undefined.