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INTRODUCTION: Pilocarpine hydrochloride (pilo) ophthalmic solution has traditionally been used for the treatment of glaucoma, with opportunities to improve the tolerability profile experienced by patients. Pilocarpine hydrochloride ophthalmic solution 1.25% (Vuity™, Allergan, an AbbVie company) was approved in late 2021 for the treatment of adults with presbyopia. This publication describes the properties of the optimized, proprietary vehicle of this new ophthalmic solution developed with the aim of improving tolerability upon instillation. METHODS: An in vitro method determined the time required for the pH of pilo 1.25% in the proprietary vehicle (Optimized Formulation) and a commercially available 1% pilo ophthalmic solution (Generic Formulation) to equilibrate with the pH of simulated tear fluid (STF). In a pilot study, five of the six screened participants received one drop of the Optimized Formulation in one eye and Generic Formulation in the other. Ocular discomfort and vision blur were evaluated for each eye just prior to and at multiple times after drop instillation using visual analog scales (VAS), and adverse events were assessed. RESULTS: The in vitro method showed that the Optimized Formulation achieved faster pH equilibration than the Generic Formulation. The pilot study revealed that the Optimized Formulation demonstrated less ocular discomfort, vision blur, and adverse events compared to the Generic. CONCLUSION: The in vitro and pilot study of the Optimized Formulation indicated that it rapidly equilibrates to the physiologic pH of the tear film, providing greater comfort and tolerability while also minimizing vision blur. Overall, the proprietary vehicle is expected to improve comfort, result in less vision blur, and provide a well-tolerated alternative method to deliver pilo for the treatment of presbyopia when compared to what is commercially available.
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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 < 0.001), whereas Oxy did not have a significant impact (P = 0.4797). The addition or increase in concentration of Oxy did not reduce incidence or severity of headaches when compared with Pilo alone. Efficacy results from the extended study supported the results from the short-term study. As early as 15 minutes postadministration, a dose response could be seen, with peak effect at 1 hour. Peak improvement increased from day 1 to day 14 and was maintained up to day 28. The most common TEAE was headache. There was no clinically significant reduction in UDVA. A polynomial regression model was developed and determined that the optimal concentration range of Pilo is between 1.16% and 1.32%. 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.