Safety and Efficacy of Twice-Daily Pilocarpine HCl in Presbyopia: The Virgo Phase 3, Randomized, Double-Masked, Controlled Study

& BULL; PURPOSE: To evaluate the safety, efficacy, and phar-macokinetics of pilocarpine hydrochloride 1.25% (Pilo hereafter) compared with vehicle when administered bi-laterally, twice daily (6 hours apart) for 14 days in par-ticipants with presbyopia. & BULL; DESIGN: Phase 3, randomized (1:1), controlled, double-masked, multicenter study. & BULL; METHODS: Participants (40-55 years of age) had ob-jective and subjective evidence of presbyopia affect-ing daily activities with mesopic, high-contrast, binoc-ular distance-corrected near visual acuity (DCNVA) of 20/40 to 20/100. The primary/key secondary endpoint was the proportion of participants gaining >3 lines in mesopic/photopic, high-contrast, binocular DCNVA on day 14 (last study visit), hour 9 (3 hours after the second dose), with no more than a 5-letter loss in mesopic/photopic corrected distance visual acuity with the same refractive correction. Key safety measures in-cluded treatment-emergent adverse events (TEAEs) and some ocular measurements. Pilocarpine plasma levels were assessed in approximately 10% of enrolled partic-ipants. & BULL; RESULTS: Overall, 230 participants were randomized to Pilo twice daily (N = 114) and vehicle (N = 116). The proportion of participants achieving the primary and key secondary efficacy endpoints was statistically significantly greater with Pilo twice daily than vehicle, with between -treatment differences of 27.3% (95% CI = 17.3, 37.4) and 26.4% (95% CI = 16.8, 36.0), respectively. The most common TEAE was headache, reported in 10 par-ticipants (8.8%, Pilo group) and 4 participants (3.4%, vehicle group). Pilocarpine's accumulation index on day 14 was & LE;1.11 after the second dose. & BULL; CONCLUSIONS: Near-vision improvements were statis-tically greater with Pilo twice daily than with vehicle, without compromising distance acuity. The safety pro-file of Pilo twice daily was consistent with that of Pilo once daily, and systemic accumulation was minimal, sup-porting twice daily administration. (Am J Ophthalmol 2023;253: 189-200. & COPY; 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/ licenses/by-nc-nd/4.0/ ))