Sepetaprost 0.002%与替莫洛尔0.5%在原发性开角型青光眼或高眼压患者中的非效性：ANGEL-2。

IF 3.2 Q1 OPHTHALMOLOGY

Ophthalmology. Glaucoma Pub Date : 2025-07-01 DOI:10.1016/j.ogla.2025.02.004

David L. Wirta MD , Sherif M. El-Harazi MD , Michael E. Tepedino MD , Jason Bacharach MD

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引用次数: 0

摘要

目的：Sepetaprost是一种新型的研究性前药，其活性形式是针对FP和EP3前列腺素受体的双重激动剂。本研究（NCT04742283）旨在证明0.002%的头孢他前列素眼液对0.5%的马酸替洛尔眼液对原发性开角型青光眼（POAG）或高眼压（OHT）患者的非效性。设计：在美国进行的一项2b期、随机、双盲、主动对照、多中心研究。参与者：共有323名成人（≥18岁）参与者(POAG, 68.4%；OHT, 31.6%)按1:1的比例随机分配，每只眼睛接受每日一次的sepetaprost （n = 162）或每日两次的噻莫洛尔（n = 161），持续3个月。方法：3次随访（第2周、第6周和第3个月），在3个时间点（8:00 AM、10:00 AM和4:00 PM）测量眼压（IOP）。主要结局指标：主要疗效终点为头孢他前列素对替洛尔的非效性。如果在所有9个指定时间点，平均IOP （sepetaprost - timolol）差异的双侧95%置信区间（CI）的上限≤1.5 mmHg，并且在9个时间点中的5个或更多时间点≤1.0 mmHg，则建立非劣效性。如果达到非劣效性，则测试优势。安全性，包括不良事件（ae）和疑似不良反应，在整个过程中进行评估。结果：达到了主要终点，在平均IOP降低方面，sepetaprost与timolol的非劣效性。在所有9个时间点，平均IOP评分组间差异的双侧95%置信区间上限均< 1.0 mmHg。在第2周、第6周和第3个月的下午4:00观察到头孢他前列素优于替洛尔；IOP平均差值（标准误差）分别为-0.76（0.302）、-‍0.73（0.328）、-0.95(0.319)，差异均有统计学意义（P < 0.05）。总体而言，接受sepetaprost的参与者中有23.6%和接受timolol的参与者中有21.3%经历ae。两组中最常见的眼部AE是结膜充血(septaprost, 9.9%；timolol, 2.5%)。结论：在POAG或OHT患者中，每日一次0.002%的泊他前列素在降低IOP方面的效果不逊于每日两次0.5%的替莫洛尔。未观察到意外的安全问题，所有ae的严重程度均为轻度或中度。

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Sepetaprost 0.002% Noninferiority vs. Timolol 0.5% in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension

Purpose

Sepetaprost is a novel investigative prodrug, the active form of which is a dual agonist targeting both prostaglandin F receptors and prostaglandin E receptor 3. This study (NCT04742283) aimed to demonstrate the noninferiority of sepetaprost ophthalmic solution 0.002% to timolol maleate ophthalmic solution 0.5% in participants with primary open-angle glaucoma (POAG) or ocular hypertension (OHT).

Design

A phase IIb, randomized, double-masked, active-controlled, multicenter study conducted in the United States.

Participants

In total, 323 adult (≥18 years) participants (POAG, 68.4%; OHT, 31.6%) were randomized 1:1 to receive either once-daily sepetaprost (n = 162) or twice-daily timolol (n = 161) in 1 eye for 3 months.

Methods

Intraocular pressure (IOP) was measured at 3 timepoints (8:00 am, 10:00 am, and 4:00 pm) at 3 visits (weeks 2 and 6 and month 3).

Main Outcome Measures

The primary efficacy endpoint was noninferiority of sepetaprost to timolol. Noninferiority was established if the upper limit of the 2-sided 95% confidence interval (CI) for the difference in mean IOP (sepetaprost minus timolol) was ≤1.5 mmHg at all 9 specified timepoints and ≤1.0 mmHg at 5 or more of the 9 timepoints. Superiority was tested if noninferiority was achieved. Safety, including adverse events (AEs) and suspected adverse reactions, was evaluated throughout.

Results

The primary endpoint, the noninferiority of sepetaprost to timolol in mean IOP reductions, was met. The upper limit of the 2-sided 95% CI for the between-group difference in mean IOP score was <1.0 mmHg at all 9 timepoints. Superiority of sepetaprost to timolol was observed at 4:00 pm in week 2, week 6, and month 3; IOP mean difference (standard error): −0.76 (0.302), –0.73 (0.328), and −0.95 (0.319), respectively (all P < 0.05). Overall, 23.6% of participants receiving sepetaprost and 21.3% receiving timolol experienced AEs. The most commonly reported ocular AE in both groups was conjunctival hyperemia (sepetaprost, 9.9%; timolol, 2.5%).

Conclusions

Once-daily sepetaprost 0.002% was statistically noninferior to twice-daily timolol 0.5% for lowering IOP in participants with POAG or OHT. There were no unexpected safety concerns observed, and all AEs were mild or moderate in severity.