Abstract：
To compare intraocular pressure (IOP)-lowering efficacy and safety of NCX 470, a nitric oxide (NO)-donating bimatoprost, to latanoprost in subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT).
Prospective, phase 3, randomized, adaptive dose-selection, double-masked, parallel-group trial.
691 subjects with OAG or OHT and unmedicated IOP ≥26 mmHg at 8AM, ≥24 mmHg at 10AM, and ≥22 mmHg at 4PM in the study eye were randomized to NCX 470 0.065%, NCX 470 0.1%, or latanoprost 0.005%. An interim analysis was performed to select the final dose of NCX 470. We evaluated noninferiority of NCX 470 versus latanoprost, based on IOP reduction from baseline at 8AM and 4PM at 2 weeks, 6 weeks, and 3 months.
661 subjects were analyzed; IOP was significantly reduced at all on-treatment time points, with reductions ranging from 8.0 to 9.7 mmHg (P < .0001 at each time point) in the NCX 470 0.1% group. Mean IOP reductions were greater with NCX 470 0.1% than latanoprost 0.005% at all 6 time points and significantly greater (P < .05) at 4 of the 6 time points. The most common adverse event was conjunctival/ocular hyperemia.
The NO-donating prostaglandin analogue NCX 470 0.1% was well-tolerated and lowered IOP more than latanoprost in subjects with OAG or OHT at all 6 time points. With a dual mechanism of action that enhances both uveoscleral and trabecular outflow, NCX 470 could become an important first-line therapy for IOP reduction in glaucoma.
Prospective, phase 3, randomized, adaptive dose-selection, double-masked, parallel-group trial.
691 subjects with OAG or OHT and unmedicated IOP ≥26 mmHg at 8AM, ≥24 mmHg at 10AM, and ≥22 mmHg at 4PM in the study eye were randomized to NCX 470 0.065%, NCX 470 0.1%, or latanoprost 0.005%. An interim analysis was performed to select the final dose of NCX 470. We evaluated noninferiority of NCX 470 versus latanoprost, based on IOP reduction from baseline at 8AM and 4PM at 2 weeks, 6 weeks, and 3 months.
661 subjects were analyzed; IOP was significantly reduced at all on-treatment time points, with reductions ranging from 8.0 to 9.7 mmHg (P < .0001 at each time point) in the NCX 470 0.1% group. Mean IOP reductions were greater with NCX 470 0.1% than latanoprost 0.005% at all 6 time points and significantly greater (P < .05) at 4 of the 6 time points. The most common adverse event was conjunctival/ocular hyperemia.
The NO-donating prostaglandin analogue NCX 470 0.1% was well-tolerated and lowered IOP more than latanoprost in subjects with OAG or OHT at all 6 time points. With a dual mechanism of action that enhances both uveoscleral and trabecular outflow, NCX 470 could become an important first-line therapy for IOP reduction in glaucoma.
摘要：
目的：比较提供一氧化氮（NO）的比马前列素NCX470降低眼压（IOP）的疗效和安全性，拉坦前列素对青光眼或高眼压患者的影响。
方法：前瞻性，第三阶段，随机，自适应剂量选择，双面蒙面,平行组试验。
方法：参与者：691名患有开角型青光眼或高眼压且8AM时IOP≥26mmHg的未用药IOP的受试者，上午10点≥24mmHg，研究眼下午4点≥22mmHg。研究程序：受试者随机接受NCX4700.065%治疗，NCX4700.1%，或拉坦前列素0.005%。为了确定最终的NCX470剂量，在每组至少30名受试者完成第2周访视后进行中期分析.注册的受试者被随机分配到最终的NCX470剂量，0.1%,或拉坦前列素12周.
方法：我们评估了NCX470与拉坦前列素的非劣效性，基于2周时8AM和4PM从基线降低的IOP，6周,和3个月。
结果：最终剂量为NCX4700.1％，分析了661名接受NCX4700.1％（n=328）或拉坦前列素（n=333）的受试者。在基线,上午8点和下午4点的平均眼压（SD）分别为28.3（2.0）mmHg和25.5（2.5）mmHg，分别,在NCX4700.1%组中，并且在所有治疗时间点都显着减少，降低范围为8.0-9.7mmHg（每个时间点p<0.0001）。同样，8AM和4PM时的平均(SD)基线眼压为28.2(2.0)mmHg和25.4(2.4)mmHg,分别,在拉坦前列素组中，在所有治疗时间点均显着降低，降低范围为7.1-9.4mmHg（每个时间点p<0.0001）。在为期三个月的访问中，在所有6个时间点,NCX为4700.1%时的平均IOP下降幅度大于拉坦前列素0.005%,在6个时间点中的4个时间点时显著更大(p<.05).在所有6个时间点建立相对于拉坦前列素的非劣效性。最常见的不良事件是结膜/眼部充血，与拉坦前列素相比，NCX470组更为常见；8名NCX470和6名拉坦前列素受试者因不良事件而停药。
结论：在所有6个时间点，在患有开角型青光眼或高眼压的受试者中，提供NO的前列腺素类似物NCX4700.1％具有良好的耐受性，并且比拉坦前列素降低了更多的IOP。具有双重作用机制，可增强葡萄膜巩膜和小梁流出，NCX470可能成为青光眼眼压降低的重要一线治疗方法。
方法：前瞻性，第三阶段，随机，自适应剂量选择，双面蒙面,平行组试验。
方法：参与者：691名患有开角型青光眼或高眼压且8AM时IOP≥26mmHg的未用药IOP的受试者，上午10点≥24mmHg，研究眼下午4点≥22mmHg。研究程序：受试者随机接受NCX4700.065%治疗，NCX4700.1%，或拉坦前列素0.005%。为了确定最终的NCX470剂量，在每组至少30名受试者完成第2周访视后进行中期分析.注册的受试者被随机分配到最终的NCX470剂量，0.1%,或拉坦前列素12周.
方法：我们评估了NCX470与拉坦前列素的非劣效性，基于2周时8AM和4PM从基线降低的IOP，6周,和3个月。
结果：最终剂量为NCX4700.1％，分析了661名接受NCX4700.1％（n=328）或拉坦前列素（n=333）的受试者。在基线,上午8点和下午4点的平均眼压（SD）分别为28.3（2.0）mmHg和25.5（2.5）mmHg，分别,在NCX4700.1%组中，并且在所有治疗时间点都显着减少，降低范围为8.0-9.7mmHg（每个时间点p<0.0001）。同样，8AM和4PM时的平均(SD)基线眼压为28.2(2.0)mmHg和25.4(2.4)mmHg,分别,在拉坦前列素组中，在所有治疗时间点均显着降低，降低范围为7.1-9.4mmHg（每个时间点p<0.0001）。在为期三个月的访问中，在所有6个时间点,NCX为4700.1%时的平均IOP下降幅度大于拉坦前列素0.005%,在6个时间点中的4个时间点时显著更大(p<.05).在所有6个时间点建立相对于拉坦前列素的非劣效性。最常见的不良事件是结膜/眼部充血，与拉坦前列素相比，NCX470组更为常见；8名NCX470和6名拉坦前列素受试者因不良事件而停药。
结论：在所有6个时间点，在患有开角型青光眼或高眼压的受试者中，提供NO的前列腺素类似物NCX4700.1％具有良好的耐受性，并且比拉坦前列素降低了更多的IOP。具有双重作用机制，可增强葡萄膜巩膜和小梁流出，NCX470可能成为青光眼眼压降低的重要一线治疗方法。
