Safety and efficacy of topical E6005, a phosphodiesterase 4 inhibitor, in Japanese adult patients with atopic dermatitis: Results of a randomized, vehicle-controlled, multicenter clinical trial
Safety and efficacy of topical E6005, a phosphodiesterase 4 inhibitor, in Japanese adult patients with atopic dermatitis: Results of a randomized, vehicle-controlled, multicenter clinical trial
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DOI：
10.1111/1346-8138.12534
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发表时间：
2014-07-01
影响因子：
3.1
通讯作者：
Nakagawa, Hidemi
中科院分区：
文献类型：
--
作者：
Furue, Masutaka;Kitahara, Yasumi;Nakagawa, Hidemi
对新型磷酸二酯酶4抑制剂E6005治疗日本成人特应性皮炎的安全性和有效性进行了评估。共有78名患者随机接受0.2%E6005软膏或赋形剂对照组(未使用E6005)，分配比为2：1。随机化阶段为4周，随后是8周的延长期。在扩展阶段，完成随机阶段的所有67名受试者都接受了0.2%E6005软膏的治疗。外用E6005，每天两次，用药4周是安全的，耐受性良好。长达12周的安全性与前4周相似。在整个12周的研究期间，没有观察到死亡或其他严重的不良反应。所有受试者在所有采样点均未检测到血浆E6005，而接受E6005治疗的受试者中有47%的受试者检测到极低浓度的E6005代谢物。4周末，外用E6005组的湿疹面积和严重程度指数(EASI)、严重程度评分特应性皮炎(SCORAD)客观评分、SCORAD-C(瘙痒和失眠的视觉模拟评分)、瘙痒行为评分以及靶向湿疹皮损的严重程度与赋形剂组相比有改善的趋势(无统计学意义)。然而，接受外用E6005治疗12周的组显示，与基线相比，EASI(P=0.030)、SCORAD-OBJECT(P<；0.001)和SCORAD-C(P=0.038)的得分显著降低。这些结果进一步支持了外用E6005治疗特应性皮炎的开发。
The safety and efficacy of topical E6005, a novel phosphodiesterase 4 inhibitor, in Japanese adults with atopic dermatitis were evaluated. A total of 78 patients were randomized to receive either the 0.2% E6005 ointment or vehicle control (without E6005) at an allocation ratio of 2:1. The randomization phase of 4 weeks was followed by an extension phase of 8 weeks. In the extension phase, all 67 subjects who completed the randomization phase were treated with 0.2% E6005 ointment. The 4-week application of topical E6005 twice daily was safe and well tolerated. The safety profile for up to 12 weeks was similar to that for the first 4 weeks. No deaths or other serious adverse effects were observed during the entire study period of 12 weeks. Plasma E6005 was undetectable in all subjects at all sampling points while very low plasma concentrations of an E6005 metabolite were detected in 47% of subjects receiving E6005 treatment. At the end of week 4, Eczema Area and Severity Index (EASI), Severity Scoring Atopic Dermatitis (SCORAD)-objective, SCORAD-C (visual analog scales for pruritus and sleep loss), itch Behavioral Rating Scale, and the severity of the targeted eczematous lesions in the topical E6005 group showed trends toward improvement compared with those in the vehicle group (not statistically significant). However, the group receiving topical E6005 for 12 weeks showed significant score reductions from baselines for EASI (P = 0.030), SCORAD-objective (P < 0.001) and SCORAD-C (P = 0.038). These results further support the development of topical E6005 for the treatment of atopic dermatitis.