Ocular hypotensive safety and systemic absorption of AR-13324 ophthalmic solution in normal volunteers

Purpose: To evaluate the ocular and systemic safety and systemic absorption of AR-13324 in normotensive, healthy volunteers.

Design: Open-label, noncomparative, single-arm phase 1 clinical trial.

Methods: setting: Phase 1 clinical trials unit. patient or study population: Eighteen normal adult volunteers. intervention or observation procedures: Subjects received AR-13324 ophthalmic solution 0.02% once daily in the morning in each eye for 8 days.

Main outcome measures: Plasma concentrations of AR-13324 and its presumed human metabolite, AR-13503, and ocular safety measures.

Results: There were no observed plasma AR-13324 concentrations higher than the lower limit of quantitation at any time point in any subject. Only 1 plasma sample from 1 subject (day 8 at 8 hours after dose administration) had an AR-13503 concentration higher than the lower limit of quantitation (0.11 ng/mL). AR-13324 dosed once daily in the morning produced substantial reductions in baseline intraocular pressure of up to 6 mm Hg that were statistically significant (P < .001) at all time points after dose administration. All but 1 subject exhibited transient conjunctival hyperemia to some degree in the 8-hour period after morning dosing.

Conclusions: AR-13324 ophthalmic solution 0.2%, administered once daily in the morning for 8 days, produced little or no quantifiable systemic exposure to the parent compound or a presumed metabolite. Clinically and statistically significant reductions in intraocular pressure were observed in these normotensive subjects that were more pronounced compared with what has been observed commonly with other ocular hypotensive therapies in this population.