Ophthalmology, University of Tokyo, Bunkyo-ku.
Santen Inc., Emeryville, CA.
J Glaucoma. 2019 May;28(5):375-385. doi: 10.1097/IJG.0000000000001221.
PRéCIS:: Three randomized, multicenter studies demonstrated the stable intraocular pressure-lowering effects and tolerability of omidenepag isopropyl in patients with primary open-angle glaucoma and ocular hypertension; 0.002% was identified as the optimal dose for further investigation.
The purpose of this study was to assess the safety and efficacy of omidenepag isopropyl, a selective EP2 agonist, and to determine the optimal dose for further investigation.
Three randomized, controlled, masked, multicenter studies were conducted in United States (study 1, NCT01868126; study 2, NCT02179008) and Japan (study 3, NCT02623738). Patients were randomized to 1 of 7 omidenepag isopropyl concentrations (0.0003%, 0.001%, 0.0012%, 0.0016%, 0.002%, 0.0025%, and 0.003%), latanoprost (0.005%), or placebo, 1 drop once daily for 28 days (studies 1 and 3) or 90 days (study 2). Primary endpoints were the observed mean diurnal intraocular pressure (IOP) and IOP at each time point on the final visit (studies 1 and 2) and change from baseline in mean diurnal IOP at week 4 (study 3).
IOP-lowering effects of omidenepag isopropyl 0.0003% to 0.002% increased dose-dependently. Omidenepag isopropyl 0.002% and 0.0025% resulted in clinically relevant mean diurnal IOP reductions from baseline that were similar to those of latanoprost and superior to placebo (P<0.005). Maximum reductions had already been achieved by week 1, and stable IOP-lowering effects were observed at all postbaseline time points up to 3 months. Most adverse events (AEs) were mild. Conjunctival hyperemia was the most frequently reported AE, the incidence of which increased dose-dependently. The safety profiles of omidenepag isopropyl 0.002% and 0.0025% were similar, with a slightly lower incidence of AEs in the 0.002% group.
Omidenepag isopropyl demonstrated stable IOP-lowering effects and was well tolerated; 0.002% was identified as the optimal dose for phase 3 investigation.
要点：三项随机、多中心研究表明，异丙基奥达尼普加在原发性开角型青光眼和高眼压患者中具有稳定的降眼压作用和耐受性；0.002%被确定为进一步研究的最佳剂量。目的：本研究旨在评估选择性 EP2 激动剂异丙基奥达尼普加的安全性和疗效，并确定进一步研究的最佳剂量。方法：在美国（研究 1，NCT01868126；研究 2，NCT02179008）和日本（研究 3，NCT02623738）进行了三项随机、对照、盲法、多中心研究。患者被随机分配至 7 种异丙基奥达尼普加浓度（0.0003%、0.001%、0.0012%、0.0016%、0.002%、0.0025%和 0.003%）、拉坦前列素（0.005%）或安慰剂组，每日 1 次滴 1 滴，持续 28 天（研究 1 和 3）或 90 天（研究 2）。主要终点为观察的平均日间眼压（IOP）和最后一次就诊时的每个时间点的 IOP（研究 1 和 2）以及第 4 周时平均日间 IOP 的基线变化（研究 3）。结果：异丙基奥达尼普加 0.0003%至 0.002%的剂量依赖性降低 IOP。异丙基奥达尼普加 0.002%和 0.0025%导致与拉坦前列素相似的、临床相关的平均日间 IOP 降低，优于安慰剂（P<0.005）。最大降低在第 1 周已经达到，在整个基线后时间点至 3 个月，均观察到稳定的降压作用。大多数不良事件（AE）为轻度。结膜充血是最常报告的 AE，其发生率呈剂量依赖性增加。异丙基奥达尼普加 0.002%和 0.0025%的安全性谱相似，0.002%组的 AE 发生率略低。结论：异丙基奥达尼普加显示出稳定的降眼压作用且耐受性良好；0.002%被确定为 3 期研究的最佳剂量。
