Six-Month Intraocular Pressure Reduction with a Topical Bimatoprost Ocular Insert Results of a Phase II Randomized Controlled Study
Six-Month Intraocular Pressure Reduction with a Topical Bimatoprost Ocular Insert Results of a Phase II Randomized Controlled Study
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DOI：
10.1016/j.ophtha.2016.04.026
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发表时间：
2016-08-01
期刊：
影响因子：
13.7
通讯作者：
Semba, Charles P.
中科院分区：
文献类型：
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作者：
Brandt, James D.;Sall, Kenneth;Semba, Charles P.
目的：提高治疗眼内压（IOP）升高的依从性仍然是一个未满足的需求。在治疗6个月的开角型青光眼（OAG）或高眼压症（OHT）患者中，将局部比马前列素眼内植入物与噻吗洛尔滴眼液每日两次进行比较。设计：单臂、多中心、双盲、随机、对照试验。1例患者在筛选洗脱期后接受比马前列素插入剂加人工泪液每日两次或安慰剂插入剂加噻吗洛尔（0.5%溶液）每日两次治疗6个月。在基线;第2、6和12周;以及第4、5和6个月获得昼夜IOP测量值（0、2和8小时）。关键的合格性包括0时洗脱期IOP ≥ 23 mmHg，2和8小时IOP ≥ 20 mmHg，所有时间点IOP ≤ 34 mmHg;既往无OAG或OHT切口手术;无已知的对奥地平无反应者。主要疗效终点检查了昼夜IOP较基线的平均变化差异使用1.5 mmHg的非劣效性界值，比较比马前列素组与噻吗洛尔组在第2、6和12周时9个共同主要终点的（点估计值，95%置信区间）。次要终点是第4、5和6个月的昼夜IOP测量值和不良事件（AEs）。结果：6个月内，比马前列素组观察到的基线IOP平均降低为-3.2至-6.4 mmHg，噻吗洛尔组为-4.2至-6.4 mmHg。该研究在2/9个时间点符合非劣效性定义，但观察到的治疗效果的把握度不足。不良事件与比马前列素或噻吗洛尔暴露一致;未观察到非预期眼部AE。插入的主要留存率为88.5%的患者在6 months.Conclusions：临床相关的平均眼压降低观察超过6个月的比马前列素眼插入，似乎是安全和耐受性良好。局部施用的比马前列素插入物可以提供每日滴眼液的替代方案，以改善粘附性、递送的一致性和降低升高的IOP。(C)2016年美国眼科学会。
Purpose: Improving adherence to manage elevated intraocular pressure (IOP) remains an unmet need. A topical bimatoprost ocular insert was compared with twice-daily timolol eye drops in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT) treated for 6 months.Design: Parallel-arm, multicenter, double-masked, randomized, controlled trial.Participants: One hundred thirty adult OAG or OHT patients.Methods: Eligible patients were randomized 1:1 to receive a bimatoprost insert plus artificial tears twice daily or a placebo insert plus timolol (0.5% solution) twice daily for 6 months after a screening washout period. Diurnal IOP measurements (at 0, 2, and 8 hours) were obtained at baseline; weeks 2, 6, and 12; and months 4, 5, and 6. Key eligibility included washout IOP of 23 mmHg or more at time 0, IOP of 20 mmHg or more at 2 and 8 hours, and IOP of 34 mmHg or less at all time points; no prior incisional surgery for OAG or OHT; and no known nonresponders to prostaglandins.Main Outcome Measures: The primary efficacy end point examined the difference in mean change from baseline in diurnal IOPs (point estimate, 95% confidence interval) across 9 coprimary end points at weeks 2, 6, and 12 comparing the bimatoprost arm with the timolol arm using a noninferiority margin of 1.5 mmHg. Secondary end points were diurnal IOP measurements at months 4, 5, and 6 and adverse events (AEs).Results: A mean reduction from baseline IOP of -3.2 to -6.4 mmHg was observed for the bimatoprost group compared with -4.2 to -6.4 mmHg for the timolol group over 6 months. The study met the noninferiority definition at 2 of 9 time points but was underpowered for the observed treatment effect. Adverse events were consistent with bimatoprost or timolol exposure; no unexpected ocular AEs were observed. Primary retention rate of the insert was 88.5% of patients at 6 months.Conclusions: Clinically relevant reduction in mean IOP was observed over 6 months with a bimatoprost ocular insert and seems to be safe and well tolerated. The topically applied bimatoprost insert may provide an alternative to daily eye drops to improve adherence, consistency of delivery, and reduction of elevated IOP. (C) 2016 by the American Academy of Ophthalmology.