ASP2151 治疗生殖器疱疹的随机、双盲、安慰剂和伐昔洛韦对照剂量研究。

ASP2151 for the treatment of genital herpes: a randomized, double-blind, placebo- and valacyclovir-controlled, dose-finding study.

机构信息

Department of Dermatology, University of Texas Health Science Center, Houston, TX, USA.

出版信息

J Infect Dis. 2012 Apr 1;205(7):1100-10. doi: 10.1093/infdis/jis019. Epub 2012 Feb 20.

DOI:10.1093/infdis/jis019

PMID:22351940

Abstract

BACKGROUND

Current therapies for genital herpes have only partial efficacy. Helicase-primase inhibitors are novel, potent inhibitors of herpes simplex virus replication.

METHODS

This randomized trial assessed the safety and efficacy of ASP2151 for episodic therapy of recurrent genital herpes. Participants self-initiated with ASP2151 (100, 200, or 400 mg daily for 3 days), ASP2151 (1200 mg as a single dose), placebo for 3 days, or valacyclovir (500 mg twice daily for 3 days). The primary efficacy endpoint, time to lesion healing excluding aborted lesions, was analyzed using a proportional hazards model. Statistical significance was determined by P = .01.

RESULTS

Of 695 adults enrolled, 437 experienced a recurrence and received study drug. Median time for lesion healing excluding aborted lesions was 139.8 hours with placebo, 119.6 hours with ASP2151 (100 mg; hazard ratio [HR], 1.40; P = .065), 106.2 with ASP2151 (200 mg; HR, 1.40; P = .081), 115.9 with ASP2151 (400 mg; HR, 1.25; P = .25), 102.1 with ASP2151 (1200 mg; HR, 1.72; P = .007), and 113.9 with valacyclovir (500 mg twice daily; HR, 1.42; P = .077), indicating improvement in all treatment groups except ASP2151 (400 mg). Incidence of treatment-emergent adverse events was similar across groups.

CONCLUSIONS

Three-day or single-day courses of ASP2151 appear to be effective and safe options for treatment of episodes of recurrent genital herpes.

CLINICAL TRIALS REGISTRATION

NCT00486200.

摘要

背景

目前治疗生殖器疱疹的方法只有部分疗效。解旋酶-引物酶抑制剂是新型、有效的单纯疱疹病毒复制抑制剂。

方法

这项随机试验评估了 ASP2151 用于治疗复发性生殖器疱疹的发作性治疗的安全性和疗效。参与者自行使用 ASP2151（100、200 或 400mg，每日 3 天）、ASP2151（1200mg 单次剂量）、安慰剂（3 天）或伐昔洛韦（500mg，每日 2 次，3 天）。主要疗效终点为排除中止性病变的皮损愈合时间，采用比例风险模型进行分析。统计学意义由 P =.01 确定。

结果

在 695 名入组的成年人中，437 名出现复发并接受了研究药物治疗。排除中止性病变后皮损愈合的中位数时间为：安慰剂组为 139.8 小时，ASP2151（100mg）组为 119.6 小时（风险比 [HR]，1.40；P =.065），ASP2151（200mg）组为 106.2 小时（HR，1.40；P =.081），ASP2151（400mg）组为 115.9 小时（HR，1.25；P =.25），ASP2151（1200mg）组为 102.1 小时（HR，1.72；P =.007），伐昔洛韦（500mg，每日 2 次）组为 113.9 小时（HR，1.42；P =.077），表明所有治疗组均有改善，除了 ASP2151（400mg）组。各组治疗中出现的不良事件发生率相似。