Sepetaprost 0.002% Noninferiority vs. Timolol 0.5% in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension: ANGEL-2.

Q2 Medicine
David L Wirta, Sherif M El-Harazi, Michael E Tepedino, Jason Bacharach
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引用次数: 0

Abstract

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.

Financial disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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。
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。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Ophthalmology. Glaucoma
Ophthalmology. Glaucoma Medicine-Medicine (all)
CiteScore
4.20
自引率
0.00%
发文量
140
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