From the Kannarr Eye Care (S.K.), Pittsburg, Kansas, USA.
Global Research Management (S.M.E.-H.), Glendale, California, USA.
Am J Ophthalmol. 2023 Sep;253:189-200. doi: 10.1016/j.ajo.2023.05.008. Epub 2023 May 5.
To evaluate the safety, efficacy, and pharmacokinetics of pilocarpine hydrochloride 1.25% (Pilo hereafter) compared with vehicle when administered bilaterally, twice daily (6 hours apart) for 14 days in participants with presbyopia.
Phase 3, randomized (1:1), controlled, double-masked, multicenter study.
Participants (40-55 years of age) had objective and subjective evidence of presbyopia affecting daily activities with mesopic, high-contrast, binocular 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 included treatment-emergent adverse events (TEAEs) and some ocular measurements. Pilocarpine plasma levels were assessed in approximately 10% of enrolled participants.
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 participants (8.8%, Pilo group) and 4 participants (3.4%, vehicle group). Pilocarpine's accumulation index on day 14 was ≤1.11 after the second dose.
Near-vision improvements were statistically greater with Pilo twice daily than with vehicle, without compromising distance acuity. The safety profile of Pilo twice daily was consistent with that of Pilo once daily, and systemic accumulation was minimal, supporting twice daily administration.
评估盐酸毛果芸香碱 1.25%（以下简称 Pilo）双侧给药、每日两次（间隔 6 小时）、连续 14 天治疗远视的安全性、疗效和药代动力学，与载体相比。
3 期、随机（1:1）、对照、双盲、多中心研究。
参与者（40-55 岁）有客观和主观证据表明远视影响日常活动，中光、高对比度、双眼矫正近视力（DCNVA）为 20/40 至 20/100。主要/关键次要终点是在第 14 天（最后一次研究访视）、第 9 小时（第二次给药后 3 小时）时，中光/明光、高对比度、双眼 DCNVA 中获得≥3 行的参与者比例，中光/明光矫正距离视力不超过 5 个字母的损失，具有相同的屈光矫正。关键安全措施包括治疗后出现的不良事件（TEAEs）和一些眼部测量。大约 10%的入组参与者评估了毛果芸香碱的血浆水平。
总体而言，230 名参与者被随机分为 Pilo 每日两次（N=114）和载体（N=116）。与载体相比，Pilo 每日两次的主要和关键次要疗效终点的比例有统计学意义上的显著增加，差异分别为 27.3%（95%CI=17.3，37.4）和 26.4%（95%CI=16.8，36.0）。最常见的不良事件是头痛，10 名参与者（8.8%，Pilo 组）和 4 名参与者（3.4%，载体组）报告了该不良事件。第二次给药后第 14 天，毛果芸香碱的累积指数≤1.11。
与载体相比，Pilo 每日两次的近视力改善具有统计学意义，且不影响远视力。Pilo 每日两次的安全性与 Pilo 每日一次一致，且系统积累最小，支持每日两次给药。
