Intraocular pressure-lowering effects and safety of topical administration of a selective ROCK inhibitor, SNJ-1656, in healthy volunteers
Intraocular pressure-lowering effects and safety of topical administration of a selective ROCK inhibitor, SNJ-1656, in healthy volunteers
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DOI：
10.1001/archophthalmol.2007.76
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发表时间：
2008-03-01
影响因子：
--
通讯作者：
Araie, Makoto
中科院分区：
文献类型：
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作者：
Tanihara, Hidenobu;Inatani, Masaru;Araie, Makoto
目的：在健康成年男性志愿者中，研究局部给药选择性Rho相关卷曲螺旋形成蛋白激酶（ROCK）抑制剂SNJ-1656（0.003%至0.1%）眼用溶液的效果和安全性。设计：随机、双盲、组比较、1期临床研究。在最初的单次滴注试验中，45名健康志愿者被随机分成5组，并以逐步方式以浓度为0.003%、0.01%、0.03%、0.05%和0.1%的SNJ-1656进行治疗。在重复滴注试验中，36名健康志愿者被分配接受以下浓度和剂量的SNJ-1656滴眼液：0.05%每日一次、0.1%每日一次、0.05%每日两次或0.1%每日两次。在我们的研究中，溶液的给药和随后的检查（包括眼内压[IOP]测量）以双盲方式进行。单次滴注安慰剂或SNJ-1656（浓度为0.003%、0.01%、0.03%、0.05%和0.1%）后，IOP相对于基线的变化分别为-0.91、-1.18、2小时时分别为-1.48、-2.20（P= 0.04 vs安慰剂）、-1.48和-1.98 mmHg，2小时时分别为-0.63、-0.95、-1.79和-2.26（P = 0.04 vs安慰剂）。01与安慰剂相比），-1.95和-3.00 mmHg（P < .001与安慰剂相比）。多次滴注后眼压也有明显下降，在裂隙灯检查中，除滴注后球结膜和睑结膜充血外，无明显不良反应。结论：本临床研究表明，SNJ-1656是一种安全有效的降眼压外用药物。
Objective: To investigate the effects and safety of topical administration of an ophthalmic solution of a selective Rho-associated coiled coil-forming protein kinase (ROCK) inhibitor, SNJ-1656, 0.003% to 0.1%, in healthy male adult volunteers.Design: Randomized, double-masked, group-comparison, phase 1 clinical study. In the initial single-instillation trial, 45 healthy volunteers were randomly subdivided into 5 groups and treated with SNJ-1656 in concentrations of 0.003%, 0.01%, 0.03%, 0.05%, and 0.1% in stepwise fashion. In the repeated-instillation trial, 36 healthy volunteers were assigned to receive SNJ-1656 ophthalmic solution at the following concentrations and dosages: 0.05% once daily, 0.1% once daily, 0.05% twice daily, or 0.1% twice daily. In our studies, the administration of the solution and subsequent examinations (including intraocular pressure [IOP] measurements) were performed in a double-masked fashion.Results: After single instillation of placebo or SNJ-1656, in concentrations of 0.003%, 0.01%, 0.03%, 0.05%, and 0.1%, the changes in IOP from the baseline were -0.91, -1.18, -1.48, -2.20 (P=.04 vs placebo), -1.48, and -1.98 mm Hg, respectively, at 2 hours, and -0.63,-0.95, -1.79, -2.26 (P =. 01 vs placebo), -1.95, and -3.00 mm Hg (P < .001 vs placebo) respectively, at 4 hours. Significant IOP reductions after repeated instillation were also found. On slitlamp examination during the trial, there were no significant adverse findings except hyperemia of the bulbar and palpebral conjunctiva after instillation.Conclusion: This clinical study demonstrated that SNJ-1656 is a safe topical agent effective in reducing IOP in human eyes.