Combinations of Pilocarpine and Oxymetazoline for the Pharmacological Treatment of Presbyopia

Purpose To determine the safety, efficacy, and tolerability of combinations of pilocarpine (Pilo) and oxymetazoline (Oxy) ocular drops dosed once daily and identify the optimal concentration of each for the pharmacologic treatment of presbyopia. Design Two concurrent Phase 2, multicenter, double-masked, randomized, vehicle-controlled studies, 1 short-term and 1 extended study. Participants Emmetropic individuals affected by presbyopia and in good general health. Methods Uncorrected near visual acuity (UNVA) was measured throughout both studies with various concentrations and combinations of Pilo (0%, 0.5% 1.0%, and 1.5%) and Oxy (0%, 0.0125%, 0.05%, and 0.125%). For safety, uncorrected distance visual acuity (UDVA) was measured, treatment-emergent adverse events (TEAEs) were recorded, and a temporal/supraorbital headache assessment was completed. Main Outcome Measures The primary efficacy end point was mean change from baseline in UNVA. Results In the short-term study, Pilo was shown to produce a significant dose response in the average increase of letters (P Conclusions On the basis of the results of the 2 Phase 2 studies, AGN-190584, a reading drop containing an optimized concentration of pilocarpine HCl (1.25%) delivered using a proprietary formulation, was developed and is currently under investigation in Phase 3 studies.