Rebamipide (OPC-12759) in the Treatment of Dry Eye: A Randomized, Double-Masked, Multicenter, Placebo-Controlled Phase II Study
Rebamipide (OPC-12759) in the Treatment of Dry Eye: A Randomized, Double-Masked, Multicenter, Placebo-Controlled Phase II Study
复制标题
DOI：
10.1016/j.ophtha.2012.06.052
复制
发表时间：
2012-12-01
期刊：
影响因子：
13.7
通讯作者：
Yokoi, Norihiko
中科院分区：
文献类型：
--
作者：
Kinoshita, Shigeru;Awamura, Saki;Yokoi, Norihiko
目标：研究1%和2%瑞巴派特眼用混悬剂与安慰剂相比治疗干眼症患者的剂量反应。设计：一项随机、双盲、多中心、安慰剂对照、平行组、剂量反应II期研究。参与者：共308例干眼症患者。方法：在2周的筛选期后，患者随机接受安慰剂或1%瑞巴派特或2%瑞巴派特，每只眼1滴，每天4次，持续4周。主要目的终点是荧光素角膜染色（FCS）评分从基线到末次观察值结转（LOCF）的变化。次要目标终点是丽丝胺绿色结膜染色（LGCS）评分、泪膜破裂时间（TBUT）和Schirmer试验。次要主观终点包括干眼相关眼部症状（异物感、干燥、眼恐怖、眼痛和视力模糊）评分和患者的总体治疗印象score.Results：观察到瑞巴派特在FCS、LGCS和TBUT评分中的剂量反应。在FCS、LGCS和TBUT评分从基线到LOCF的变化方面，1%和2%瑞巴派特均比安慰剂显著更有效。瑞巴派特组和安慰剂组之间从基线到LOCF的Schirmer检验值没有显著差异，并且没有观察到剂量反应。在基线FCS评分为10 - 15的预定义干眼亚群中，2%瑞巴派特组较基线的平均变化大于1%瑞巴派特组。从基线到LOCF的所有5个干眼相关眼部症状评分和患者的总体治疗印象的变化显示，与安慰剂组相比，1%和2%瑞巴派特组有显著改善，除了1%瑞巴派特组的畏光症。任何治疗组均未发生死亡或药物相关严重不良事件。在瑞巴派特和安慰剂groups.Conclusions：瑞巴派特是有效的治疗干眼症的客观体征和主观症状，并在这4周的研究耐受性良好的眼部异常的发病率是相似的。虽然1%和2%瑞巴派特都是有效的，2%瑞巴派特可能比1%瑞巴派特在某些措施更有效。Ophthalmology 2012;119：2471-2478（C）2012，美国眼科学会。
Objective: To investigate the dose response for efficacy of 1% and 2% rebamipide ophthalmic suspension compared with placebo in patients with dry eye.Design: A randomized, double-masked, multicenter, placebo-controlled, parallel-group, dose-response phase II study.Participants: A total of 308 patients with dry eye.Methods: After a 2-week screening period, patients were randomized to receive placebo or 1% rebamipide or 2% rebamipide administered as 1 drop in each eye 4 times daily for 4 weeks.Main Outcome Measures: The primary objective end point was change in fluorescein corneal staining (FCS) score from baseline to last observation carried forward (LOCF). Secondary objective end points were lissamine green conjunctival staining (LGCS) score, tear film break-up time (TBUT), and the Schirmer's test. Secondary subjective end points included dry eye-related ocular symptoms (foreign body sensation, dryness, photophobia, eye pain, and blurred vision) score and patients' overall treatment impression score.Results: Rebamipide dose response was observed in FCS, LGCS, and TBUT scores. Both 1% and 2% rebamipide were significantly more effective than the placebo in terms of the change from baseline to LOCF for FCS, LGCS, and TBUT scores. There was no significant difference between the rebamipide and placebo groups from baseline to LOCF in Schirmer's test values, and dose response was not observed. In the predefined dry eye subpopulation with a baseline FCS score of 10 to 15, the mean change from baseline in the 2% rebamipide group was larger than that in the 1% rebamipide group. Change from baseline to LOCF for all 5 dry eye-related ocular symptom scores and patients' overall treatment impression showed significant improvements in the 1% and 2% rebamipide groups compared with the placebo group, except for photophobia in the 1% rebamipide group. No deaths or drug-related serious adverse events occurred in any treatment group. The incidence of ocular abnormalities was similar across the rebamipide and placebo groups.Conclusions: Rebamipide was effective in treating both objective signs and subjective symptoms of dry eye and were well tolerated in this 4-week study. Although 1% and 2% rebamipide were both efficacious, 2% rebamipide may be more effective than 1% rebamipide in some measures.Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2012;119:2471-2478 (C) 2012 by the American Academy of Ophthalmology.