Long-Term Safety and Efficacy Evaluation of Travoprost Intracameral Implant Based on Pooled Analyses from Two Phase III Trials.

IF 13 1区 医学 Q1 PHARMACOLOGY & PHARMACY Drugs Pub Date : 2024-10-01 Epub Date: 2024-09-06 DOI:10.1007/s40265-024-02074-9
I Paul Singh, John P Berdahl, Steven R Sarkisian, Lilit A Voskanyan, Robert E Ang, Long V Doan, David Applegate, Yannan Shen, L Jay Katz, Angela C Kothe, Tomas Navratil
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Abstract

Aim: The purpose of this study was to conduct and interpret a pooled 12-month analysis of two prospective, multi-center, randomized, double-masked, controlled trials designed to assess the efficacy and safety of the travoprost intracameral implant (slow-eluting [SE] implant in development as a new therapeutic and fast-eluting [FE] implant included for masking purposes) in subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT).

Methods: Subjects with OAG or OHT, on 0-3 intraocular pressure (IOP)-lowering medications, baseline unmedicated mean diurnal IOP of ≥ 21 mmHg, and IOP ≤ 36 mmHg at each baseline diurnal timepoint, received either a travoprost implant and twice-daily (BID) placebo eye drops or BID timolol 0.5% eye drops and a sham procedure. Subjects were followed through 12 months and assessed for IOP, reduction in topical IOP-lowering medications, and safety parameters including treatment-emergent adverse events (TEAEs). IOP at 8AM was prospectively collected at all study visits through 12 months and diurnal IOP, measured at 8AM, 10AM, and 4PM, was prospectively collected at baseline, day 10, week 6, and months 3 and 12.

Results: A total of 1150 subjects were randomized (385 FE implant, 380 SE implant, and 385 sham/timolol) across the two trials. Statistical non-inferiority to timolol and clinically relevant reductions in 8AM IOPs were demonstrated at month 12. In more detail, both implant groups demonstrated statistical non-inferiority to timolol and clinically relevant reductions from baseline in mean diurnal IOP at all visits over the 12-month evaluation period when diurnal IOP was collected. Additionally, both implant groups demonstrated robust treatment effect based on 8AM average IOP from day 10 through the specified visit which ranged from day 10 to month 12 from 6.9 to 8.5 mmHg in the FE implant group; 6.8 to 8.5 mmHg in the SE implant group; and 7.3 to 7.5 mmHg in the sham/timolol group. With regards to reduction in topical pharmacotherapy, at month 12, 77.6% of FE and 81.4% of SE implant eyes were completely free of all topical IOP-lowering medications and a significantly greater proportion of FE and SE implant eyes (89.9% and 93.0%) versus sham/timolol eyes (66.9%) were on the same or fewer topical IOP-lowering medications compared with pre-study (p <  0.0001). Furthermore, of subjects on topical IOP medications at screening, a significantly greater proportion of FE implant (80.2%) and SE implant (85.1%) eyes versus sham/timolol (22.8%) eyes were on fewer topical IOP-lowering medications at month 12 compared with pre-study (p <  0.0001). Lastly, of SE implant eyes on same or fewer topical IOP-lowering medications at month 12, the average through month 12 decreased by 0.9 medications, and of those SE implant eyes on fewer topical IOP-lowering medications compared with pre-study, the average through month 12 decreased by 1.4 medications. The most common TEAEs related to study treatment were hyperemia (conjunctival or ocular), iritis, and IOP increased.

Conclusion: The travoprost intracameral implant demonstrated robust IOP-lowering efficacy that was sustained and statistically non-inferior to timolol over the entire 12 months, resulting in a significant reduction in topical IOP-lowering medication use, with the majority of SE implant eyes remaining completely free of all topical IOP-lowering medications. In addition, the implant demonstrated a favorable safety and tolerability profile based on this pooled 12-month analysis of two pivotal trials.

Trial registration: ClinicalTrials.gov identifiers NCT03519386 (registered May 09, 2018) and NCT03868124 (registered March 08, 2019).

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基于两项 III 期试验的汇总分析,对曲伏前列素巩膜内植入物进行长期安全性和有效性评估。
目的:本研究的目的是对两项前瞻性、多中心、随机、双掩蔽对照试验进行为期12个月的汇总分析,评估曲伏前列素巩膜内植入物(慢洗脱[SE]植入物作为一种新疗法正在开发中,快速洗脱[FE]植入物用于掩蔽目的)在开角型青光眼(OAG)或眼压过高(OHT)受试者中的疗效和安全性:方法:患有开角型青光眼(OAG)或眼压过高(OHT)的受试者,正在服用0-3种降低眼压(IOP)的药物,基线未用药的平均昼夜眼压≥21 mmHg,且每个基线昼夜时间点的眼压≤36 mmHg,接受曲伏前列素植入剂和每日两次(BID)安慰剂滴眼液,或每日两次(BID)噻吗洛尔0.5%滴眼液和假手术。对受试者进行为期 12 个月的随访,并评估其眼压、局部降眼压药物用量的减少情况以及包括治疗突发不良事件 (TEAE) 在内的安全性参数。在为期 12 个月的所有研究访问中都会收集上午 8 点的眼压数据,并在基线、第 10 天、第 6 周、第 3 个月和第 12 个月收集上午 8 点、上午 10 点和下午 4 点的昼夜眼压数据:在两项试验中,共有 1150 名受试者(385 名 FE 植入者、380 名 SE 植入者和 385 名假噻吗洛尔/噻吗洛尔)接受了随机治疗。第 12 个月时,8AM 眼压的降低在统计学上不劣于噻吗洛尔,且与临床相关。更详细地说,在为期 12 个月的评估期间,在收集昼夜眼压的所有访问中,两组植入物均显示出统计学上不劣于噻吗洛尔,且平均昼夜眼压较基线有临床相关性降低。此外,根据从第 10 天到指定就诊时间的上午 8 点平均眼压,两组植入物均显示出良好的治疗效果,从第 10 天到第 12 个月,FE 植入物组的平均眼压为 6.9 至 8.5 mmHg;SE 植入物组为 6.8 至 8.5 mmHg;假体/噻吗洛尔组为 7.3 至 7.5 mmHg。在减少局部药物治疗方面,第 12 个月时,77.6% 的 FE 和 81.4% 的 SE 植入眼完全没有使用所有局部降眼压药物,与研究前相比,FE 和 SE 植入眼(89.9% 和 93.0%)使用相同或更少的局部降眼压药物的比例明显高于假体/噻吗洛尔眼(66.9%)(p < 0.0001)。此外,在筛查时使用局部降眼压药物的受试者中,与研究前相比,在第 12 个月时,FE 植入眼(80.2%)和 SE 植入眼(85.1%)使用局部降眼压药物的比例明显高于假体/噻吗洛尔(22.8%)(p < 0.0001)。最后,与研究前相比,在第 12 个月使用相同或更少的局部降眼压药物的 SE 植入眼中,第 12 个月平均减少了 0.9 种药物,而在第 12 个月使用更少局部降眼压药物的 SE 植入眼中,第 12 个月平均减少了 1.4 种药物。与研究治疗相关的最常见TEAE是高眼压血症(结膜或眼球)、虹膜炎和眼压升高:结论:曲伏前列素巩膜内植入剂具有强大的降眼压疗效,在整个12个月的疗程中,疗效持续且在统计学上不劣于噻吗洛尔,从而显著减少了局部降眼压药物的使用,大多数SE植入眼完全无需使用所有局部降眼压药物。此外,根据对两项关键性试验进行的为期 12 个月的汇总分析,该植入物显示出良好的安全性和耐受性:试验注册:ClinicalTrials.gov标识符NCT03519386(2018年5月9日注册)和NCT03868124(2019年3月8日注册)。
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来源期刊
Drugs
Drugs 医学-毒理学
CiteScore
22.70
自引率
0.90%
发文量
134
审稿时长
3-8 weeks
期刊介绍: Drugs is a journal that aims to enhance pharmacotherapy by publishing review and original research articles on key aspects of clinical pharmacology and therapeutics. The journal includes: Leading/current opinion articles providing an overview of contentious or emerging issues. Definitive reviews of drugs and drug classes, and their place in disease management. Therapy in Practice articles including recommendations for specific clinical situations. High-quality, well designed, original clinical research. Adis Drug Evaluations reviewing the properties and place in therapy of both newer and established drugs. AdisInsight Reports summarising development at first global approval. Moreover, the journal offers additional digital features such as animated abstracts, video abstracts, instructional videos, and podcasts to increase visibility and educational value. Plain language summaries accompany articles to assist readers with some knowledge of the field in understanding important medical advances.
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