一项关于他氟前列素异丙酯（PF-04217329）与拉坦前列素 0.005%在开角型青光眼和高眼压症中进行的 2 期、随机、剂量反应试验。

A phase 2, randomized, dose-response trial of taprenepag isopropyl (PF-04217329) versus latanoprost 0.005% in open-angle glaucoma and ocular hypertension.

机构信息

Pfizer Inc, San Diego, California 92121, USA.

出版信息

Curr Eye Res. 2011 Sep;36(9):809-17. doi: 10.3109/02713683.2011.593725.

DOI:10.3109/02713683.2011.593725

PMID:21851167

Abstract

PURPOSE

To evaluate the safety of escalating doses of taprenepag isopropyl (PF-04217329), a selective EP(2) receptor agonist administered as a topical ophthalmic solution, versus its vehicle (Stage I), and dose-response of taprenepag isopropyl alone and in unfixed combination with latanoprost ophthalmic solution 0.005% versus latanoprost alone (Stage II).

SUBJECTS AND METHODS

Randomized, vehicle- and active-controlled, double-masked, two-stage, dose-finding trial in primary open-angle glaucoma (POAG) or ocular hypertension; first taprenepag isopropyl study in patients (NCT00572455). Study eye: 26 mmHg ≤ intraocular pressure (IOP) <36 mmHg at 8 am and 22 mmHg ≤ IOP <36 mmHg at 10 am, 1 pm, 4 pm. Stage I: 3 cohorts (total n = 67) received 1 drop of taprenepag isopropyl unit dose formulation qPM/eye for 14 days: low dose: 0.0025%, 0.005%, vehicle; middle dose: 0.01%, 0.015%, vehicle; high dose: 0.02%, 0.03%, vehicle. Stage II: 7 groups (total n = 250) received 1 drop of taprenepag isopropyl multidose formulation qPM/eye for 28 days: 0.005%, 0.01%, 0.015% monotherapy; each in unfixed combination with latanoprost 0.005%, or latanoprost monotherapy.

MAIN OUTCOMES

mean change in diurnal IOP, baseline to last visit; adverse events.

RESULTS

Stage I at day 14: statistically significantly greater IOP reductions were observed at all taprenepag isopropyl doses versus vehicle. Stage II at day 28: statistically significantly greater IOP reductions were observed at all doses of the unfixed combination versus latanoprost monotherapy. At least 1 treatment-emergent adverse event reported for 29/67 (43.3%) subjects in Stage I and 158/250 (63.2%) in Stage II.

CONCLUSIONS

Taprenepag isopropyl significantly reduces IOP in POAG and ocular hypertension. Taprenepag isopropyl monotherapy is comparable to latanoprost 0.005% in reducing IOP. As demonstrated in this report, the activity of taprenepag isopropyl is additive to that of latanoprost 0.005%. Further studies are required to determine whether it shows similar additivity when administered with other ocular antihypertensive medications.

摘要

目的

评估作为局部眼用溶液给予的选择性 EP（2）受体激动剂 taprenepag 异丙酯（PF-04217329）递增剂量的安全性，与载体相比（I 期），以及 taprenepag 异丙酯单独和与拉坦前列素眼用溶液 0.005% 固定组合与拉坦前列素单独的剂量反应（II 期）。

对象和方法

原发性开角型青光眼（POAG）或高眼压的随机、载体和活性对照、双盲、两阶段、剂量发现试验；首次在患者中进行 taprenepag 异丙酯研究（NCT00572455）。研究眼：8 点时眼内压（IOP）为 26 mmHg≤IOP<36 mmHg，上午 10 点时 IOP 为 22 mmHg≤IOP<36 mmHg。I 期：3 个队列（共 67 名患者）接受 1 滴 taprenepag 异丙酯单剂量制剂 qPM/眼，持续 14 天：低剂量：0.0025%、0.005%、载体；中剂量：0.01%、0.015%、载体；高剂量：0.02%、0.03%、载体。II 期：7 组（共 250 名患者）接受 1 滴 taprenepag 异丙酯多剂量制剂 qPM/眼，持续 28 天：0.005%、0.01%、0.015%单药治疗；每种药物均与拉坦前列素 0.005%固定组合，或拉坦前列素单药治疗。

主要结局

白天 IOP 的平均变化，从基线到最后一次就诊；不良事件。

结果

第 I 阶段第 14 天：与载体相比，所有 taprenepag 异丙酯剂量均观察到统计学上显著更大的 IOP 降低。第 II 阶段第 28 天：与拉坦前列素单药治疗相比，所有固定组合的剂量均观察到统计学上显著更大的 IOP 降低。第 I 阶段有 29/67（43.3%）名患者至少报告了 1 种治疗后出现的不良事件，第 II 阶段有 158/250（63.2%）名患者报告了 1 种治疗后出现的不良事件。

结论

Taprenepag 异丙酯可显著降低 POAG 和高眼压患者的 IOP。Taprenepag 异丙酯单药治疗与拉坦前列素 0.005%降低 IOP 相当。正如本报告所示，taprenepag 异丙酯的活性与拉坦前列素 0.005%相加。需要进一步研究以确定其与其他眼部降压药物联合使用时是否表现出相似的相加作用。