Abstract：
OBJECTIVE: To evaluate the safety and intraocular pressure (IOP)-lowering efficacy of 2 models of the travoprost intraocular implant (fast-eluting [FE] and slow-eluting [SE] types) from 1 of 2 phase 3 trials (the GC-010 trial).
METHODS: Multicenter, randomized, double-masked, sham-controlled, noninferiority trial.
METHODS: Patients with open-angle glaucoma or ocular hypertension having an unmedicated baseline mean diurnal IOP (average of 8 am, 10 am, and 4 pm time points) of ≥ 21 mmHg, and IOP of ≤ 36 mmHg at each of the 8 am, 10 am, and 4 pm timepoints at baseline.
METHODS: Study eyes were randomized to the travoprost intraocular implant (FE implant [n = 200] or SE implant [n = 197] model) or to timolol ophthalmic solution 0.5% twice daily (n = 193).
METHODS: The primary outcome was mean change from baseline IOP in the study eye at 8 am and 10 am, at each of day 10, week 6, and month 3. Safety outcomes included adverse events (AEs) and ophthalmic assessments.
RESULTS: Mean IOP reduction from baseline over the 6 time points ranged from 6.6 to 8.4 mmHg for the FE implant group, from 6.6 to 8.5 mmHg for the SE implant group, and from 6.5 to 7.7 mmHg for the timolol group. The primary efficacy end point was met; the upper limit of the 95% confidence interval of the difference between the implant groups and the timolol group was < 1 mmHg at all 6 time points. Study eye AEs, most of mild or moderate severity, were reported in 21.5%, 27.2%, and 10.8% of patients in the FE implant, SE implant, and timolol groups, respectively. The most common AEs included iritis (FE implant, 0.5%; SE implant, 5.1%), ocular hyperemia (FE implant, 3.0%; SE implant, 2.6%), reduced visual acuity (FE implant, 1.0%; SE implant, 4.1%; timolol, 0.5%), and IOP increased (FE implant, 3.5%; SE implant, 2.6%; timolol, 2.1%). One serious study eye AE occurred (endophthalmitis).
CONCLUSIONS: The travoprost intraocular implant demonstrated robust IOP reduction over the 3-month primary efficacy evaluation period after a single administration. The IOP-lowering efficacy in both implant groups was statistically and clinically noninferior to that in the timolol group, with a favorable safety profile.
BACKGROUND: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
METHODS: Multicenter, randomized, double-masked, sham-controlled, noninferiority trial.
METHODS: Patients with open-angle glaucoma or ocular hypertension having an unmedicated baseline mean diurnal IOP (average of 8 am, 10 am, and 4 pm time points) of ≥ 21 mmHg, and IOP of ≤ 36 mmHg at each of the 8 am, 10 am, and 4 pm timepoints at baseline.
METHODS: Study eyes were randomized to the travoprost intraocular implant (FE implant [n = 200] or SE implant [n = 197] model) or to timolol ophthalmic solution 0.5% twice daily (n = 193).
METHODS: The primary outcome was mean change from baseline IOP in the study eye at 8 am and 10 am, at each of day 10, week 6, and month 3. Safety outcomes included adverse events (AEs) and ophthalmic assessments.
RESULTS: Mean IOP reduction from baseline over the 6 time points ranged from 6.6 to 8.4 mmHg for the FE implant group, from 6.6 to 8.5 mmHg for the SE implant group, and from 6.5 to 7.7 mmHg for the timolol group. The primary efficacy end point was met; the upper limit of the 95% confidence interval of the difference between the implant groups and the timolol group was < 1 mmHg at all 6 time points. Study eye AEs, most of mild or moderate severity, were reported in 21.5%, 27.2%, and 10.8% of patients in the FE implant, SE implant, and timolol groups, respectively. The most common AEs included iritis (FE implant, 0.5%; SE implant, 5.1%), ocular hyperemia (FE implant, 3.0%; SE implant, 2.6%), reduced visual acuity (FE implant, 1.0%; SE implant, 4.1%; timolol, 0.5%), and IOP increased (FE implant, 3.5%; SE implant, 2.6%; timolol, 2.1%). One serious study eye AE occurred (endophthalmitis).
CONCLUSIONS: The travoprost intraocular implant demonstrated robust IOP reduction over the 3-month primary efficacy evaluation period after a single administration. The IOP-lowering efficacy in both implant groups was statistically and clinically noninferior to that in the timolol group, with a favorable safety profile.
BACKGROUND: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
摘要：
目的：从两项关键试验（GC-010）之一中评估曲伏前列素眼内植入物（快速洗脱[FE-植入物]和缓慢洗脱[SE-植入物]）的两种模型的安全性和降低眼内压（IOP）的功效。
方法：第三阶段，多中心，随机化，双面蒙面,假控制，非自卑审判。
方法：患有开角型青光眼或高眼压的受试者，在筛查时使用0至3种降低IOP的药物，并且具有未用药的基线平均昼夜IOP（平均8AM，10AM和4PM时间点)≥21mmHg，在研究眼的每个时间点，未用药的基线IOP≤36mmHg。
方法：研究的眼睛被随机分配到曲伏前列素眼内植入物（FE植入物[n=200]或SE植入物[n=197]模型）加上每日两次（BID）安慰剂滴眼液，或假手术加噻吗洛尔眼用溶液，0.5%BID(n=193)。
方法：主要结果是研究眼睛在8AM和10AM时与基线眼压的平均变化，在第10天、第6周和第3个月中的每一天。安全性结果包括不良事件（AE），角膜内皮细胞计数，视敏度,和结膜充血评估。
结果：FE植入组6个时间点的平均眼压相对于基线的降低范围为6.6-8.4mmHg，SE植入组从6.6到8.5mmHg，噻吗洛尔组从6.5到7.7mmHg。达到主要疗效终点；在所有6个时间点，植入物组和噻吗洛尔组之间的差异的95％置信区间的上限均<1mmHg。研究眼睛AE，大多数轻度或中度严重程度，报告为21.5%，在FE植入物中，有27.2%和10.8%的受试者，SE-植入物和噻吗洛尔组，分别。最常见的AE包括虹膜炎(FE植入物，0.5%;SE植入,5.1%)，眼部充血(FE-植入物，3.0%;SE-植入,2.6%），视力降低(FE-植入物，1.0%；SE-植入，4.1%；噻吗洛尔，0.5%），和IOP增加(FE植入物，3.5%;SE植入,2.6%；噻吗洛尔，2.1%）。有一个严重的研究眼睛AE（眼内炎）。
结论：在单次给药后的3个月主要疗效评估期内，曲伏前列素眼内植入物显示出稳定的IOP降低。两个植入物组的眼压降低疗效在统计学和临床上都不劣于噻吗洛尔组。具有良好的安全性。
方法：第三阶段，多中心，随机化，双面蒙面,假控制，非自卑审判。
方法：患有开角型青光眼或高眼压的受试者，在筛查时使用0至3种降低IOP的药物，并且具有未用药的基线平均昼夜IOP（平均8AM，10AM和4PM时间点)≥21mmHg，在研究眼的每个时间点，未用药的基线IOP≤36mmHg。
方法：研究的眼睛被随机分配到曲伏前列素眼内植入物（FE植入物[n=200]或SE植入物[n=197]模型）加上每日两次（BID）安慰剂滴眼液，或假手术加噻吗洛尔眼用溶液，0.5%BID(n=193)。
方法：主要结果是研究眼睛在8AM和10AM时与基线眼压的平均变化，在第10天、第6周和第3个月中的每一天。安全性结果包括不良事件（AE），角膜内皮细胞计数，视敏度,和结膜充血评估。
结果：FE植入组6个时间点的平均眼压相对于基线的降低范围为6.6-8.4mmHg，SE植入组从6.6到8.5mmHg，噻吗洛尔组从6.5到7.7mmHg。达到主要疗效终点；在所有6个时间点，植入物组和噻吗洛尔组之间的差异的95％置信区间的上限均<1mmHg。研究眼睛AE，大多数轻度或中度严重程度，报告为21.5%，在FE植入物中，有27.2%和10.8%的受试者，SE-植入物和噻吗洛尔组，分别。最常见的AE包括虹膜炎(FE植入物，0.5%;SE植入,5.1%)，眼部充血(FE-植入物，3.0%;SE-植入,2.6%），视力降低(FE-植入物，1.0%；SE-植入，4.1%；噻吗洛尔，0.5%），和IOP增加(FE植入物，3.5%;SE植入,2.6%；噻吗洛尔，2.1%）。有一个严重的研究眼睛AE（眼内炎）。
结论：在单次给药后的3个月主要疗效评估期内，曲伏前列素眼内植入物显示出稳定的IOP降低。两个植入物组的眼压降低疗效在统计学和临床上都不劣于噻吗洛尔组。具有良好的安全性。
