Kanto Central Hospital of the Mutual Aid Association of Public School Teachers, Tokyo, Japan.
Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan.
Adv Ther. 2021 Apr;38(4):1757-1775. doi: 10.1007/s12325-021-01634-9. Epub 2021 Feb 24.
Netarsudil reduces intraocular pressure (IOP) by increasing aqueous outflow through the trabecular meshwork (TM) pathway and decreasing episcleral venous pressure. The primary objective of this phase 2 study was to evaluate ocular hypotensive efficacy and safety of three netarsudil concentrations (0.01%, 0.02%, and 0.04%) relative to its placebo over 4 weeks in Japanese patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT).
Patients were randomized to one of four treatment arms, netarsudil ophthalmic solution 0.01%, 0.02%, 0.04%, or placebo, and treated once-daily (QD) in the evening (P.M.) for 4 weeks. The primary efficacy variable was mean diurnal IOP (average of diurnal time points at 9 A.M., 11 A.M., and 4 P.M.) at week 4.
A total of 215 patients were randomized and 207 (96.3%) completed the study. The mean of mean diurnal IOP at baseline ranged from 20.28 to 21.14 mmHg across groups. At week 4, least squares (LS) mean of mean diurnal IOP adjusted for baseline was 16.53, 15.82, 16.06, and 18.94 mmHg in the netarsudil 0.01%, 0.02%, 0.04%, and placebo groups, respectively, demonstrating the superiority of netarsudil (all concentrations) over placebo. At week 4, mean reduction (mean percentage reduction) from baseline in mean diurnal IOP was 4.10 (19.8%), 4.80 (23.5%), 4.81 (23.8%), and 1.73 mmHg (8.2%), respectively, demonstrating statistically significant reductions (p < 0.0001) in all netarsudil concentrations over placebo. Adverse events (AEs) occurred in a concentration-dependent manner, and the incidence of ocular AEs was 34.5%, 42.6%, 68.6%, and 9.1% in the netarsudil 0.01%, 0.02%, 0.04%, and placebo groups, respectively. The most frequently reported AE was conjunctival hyperemia, with an incidence of 23.6%, 37.0%, 56.9%, and 1.8%, respectively. No serious AEs were reported.
Netarsudil ophthalmic solutions 0.01%, 0.02%, and 0.04% dosed QD (P.M.) demonstrated superiority to placebo in terms of hypotensive effectiveness at week 4 and were found to be safe and generally well tolerated. Netarsudil 0.02% QD provided an optimal efficacy and safety profile for the treatment of Japanese patients with POAG or OHT.
NCT03844945.
奈拉苏地尔通过增加房水通过小梁网（TM）途径的流出以及降低巩膜静脉压来降低眼内压（IOP）。本 2 期研究的主要目的是评估奈拉苏地尔三种浓度（0.01%、0.02%和 0.04%）相对于安慰剂在 4 周内对原发性开角型青光眼（POAG）或高眼压症（OHT）日本患者的降眼压疗效和安全性。
患者随机分为四组治疗组，奈拉苏地尔滴眼液 0.01%、0.02%、0.04%或安慰剂，每晚（PM）一次（QD）治疗 4 周。主要疗效变量为第 4 周的平均日间眼压（9 AM、11 AM 和 4 PM 时的日间时间点的平均值）。
共有 215 名患者被随机分组，207 名（96.3%）完成了研究。基线时平均日间眼压的平均值在各组之间从 20.28 至 21.14 mmHg 不等。第 4 周时，奈拉苏地尔 0.01%、0.02%、0.04%和安慰剂组的平均日间眼压调整后的最小二乘（LS）均值分别为 16.53、15.82、16.06 和 18.94 mmHg，表明奈拉苏地尔（所有浓度）优于安慰剂。第 4 周时，与基线相比，平均日间眼压的平均降低（平均百分比降低）分别为 4.10（19.8%）、4.80（23.5%）、4.81（23.8%）和 1.73 mmHg（8.2%），表明所有奈拉苏地尔浓度相对于安慰剂均具有统计学显著降低（p<0.0001）。不良反应（AE）呈浓度依赖性，奈拉苏地尔 0.01%、0.02%、0.04%和安慰剂组的眼 AE 发生率分别为 34.5%、42.6%、68.6%和 9.1%。最常报告的 AE 是结膜充血，发生率分别为 23.6%、37.0%、56.9%和 1.8%。未报告严重 AE。
奈拉苏地尔滴眼液 0.01%、0.02%和 0.04%QD（PM）在第 4 周时在降压效果方面优于安慰剂，且安全性良好，一般耐受良好。奈拉苏地尔 0.02%QD 为治疗日本 POAG 或 OHT 患者提供了最佳的疗效和安全性。
NCT03844945。
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