TY - JOUR T1 - Ocular hypotensive efficacy, safety and systemic absorption of AR-12286 ophthalmic solution in normal volunteers JF - British Journal of Ophthalmology JO - Br J Ophthalmol SP - 567 LP - 572 DO - 10.1136/bjophthalmol-2012-302466 VL - 97 IS - 5 AU - Casey Kopczynski AU - Gary D Novack AU - Dennis Swearingen AU - Thomas van Haarlem Y1 - 2013/05/01 UR - http://bjo.bmj.com/content/97/5/567.abstract N2 - Background/aims To evaluate the ocular hypotensive efficacy, ocular and systemic safety, and systemic exposure of two formulations of 0.5% AR-12286 Ophthalmic Solution. Methods This was a double-masked, single-centre, crossover study in 18 normal adult volunteers. Volunteers were randomised to one of two dosing sequences: Formulation A once daily, both eyes (OU) for 8 days, a 7-day minimum washout, and then Formulation B, or the reverse. The main outcome measures were ocular tolerability, intraocular pressure (IOP) and blood levels of AR-12286 and its metabolites. Results Systemic absorption was low, with a majority of subjects showing no measurable drug concentration in plasma (<1 ng/ml) at any time point with either formulation. The most frequent ocular adverse events were conjunctival hyperaemia, eye irritation, instillation site reaction, increased lacrimation, and blurred vision which were relatively short-lived and judged as not clinically significant. Both formulations of AR-12286 produced substantial reductions from baseline IOP ranging from 3 to 7 mm Hg (p<0.0001). Conclusions No differences were noted in ocular safety between formulations of AR-12286 0.5%, dosed once daily in the morning for 8 days. AR-12286 produced little systemic exposure to the parent compound or two known metabolites. Clinically and statistically significant reductions in IOP were seen in these normotensive subjects. ER -