奥替康唑（VT-1161）治疗皮肤癣菌性趾甲甲真菌病：II期试验亚组疗效及延长随访安全性综述。
完整摘要 · 中文译文
奥替康唑是一种合成的四唑类抗真菌药，其药理学优势提示它可成为红色毛癣菌甲真菌病安全有效的治疗方法。奥替康唑（VT-1161）治疗甲真菌病的II期研究显示，在受试给药方案至第60周具有良好的疗效和安全性：300 mg 12周；300 mg 24周；600 mg 12周和600 mg 24周（所有方案均先每日一次给药2周，之后剩余周每周一次）。使用可能影响甲真菌病的患者因素进行了额外的疗效分析。在所有四种受试方案中观察到相似的有效率。患者因素（年龄<50岁、受累甲面积<50%）与结局改善的相关性强于奥替康唑剂量增加，但不一定预测总体结局更好。截至第60周未发现显著安全性问题。从第60周到第96周的新延长随访数据显示奥替康唑长期血浆滞留，且无额外奥替康唑相关不良事件。因此，第72周和第96周的临床照片评估显示目标趾甲改善；然而，可评估患者数量有限（n = 22），且未进行真菌学检查。与传统的唑类（伊曲康唑、氟康唑）相比，奥替康唑的四唑结构显著降低药物相互作用风险。良好的安全性和有效性特征表明，奥替康唑可能成为伊曲康唑用于甲真菌病的潜在替代选择，在任何受试的 剂量。
完整摘要 · 英文原文
Oteseconazole, a synthetic tetrazole antifungal, provides pharmacological advantages that suggest it can be a safe and effective treatment for Trichophyton rubrum onychomycosis. A Phase II study of oteseconazole (VT-1161) for onychomycosis demonstrated good efficacy and safety up to Week 60 in the dosing regimens tested: 300 mg for 12 weeks; 300 mg for 24 weeks; 600 mg for 12 weeks and 600 mg for 24 weeks (all given once daily for 2 weeks, then once weekly for remaining weeks). Additional analysis of efficacy was performed using patient factors that can impact onychomycosis. Similar efficacy rates were found across all four regimens tested. Patient factors (<50 years of age, <50% affected nail area) were more strongly associated with improved outcomes than dose escalation of oteseconazole but did not necessarily predict better overall outcomes. No significant safety concerns were found up to Week 60. New extended follow-up data from Week 60 to Week 96 demonstrated long-term plasma retention of oteseconazole with no additional oteseconazole-related adverse events. Accordingly, clinical photographic assessment at Weeks 72 and 96 showed improvement in the target toenail; however, the number of evaluable patients was limited (n = 22), and mycology testing was not performed. The tetrazole structure of oteseconazole significantly reduces the risk of drug-drug interaction compared to traditional azoles (itraconazole, fluconazole). The favorable safety and efficacy profile suggests oteseconazole could be a potential alternative to itraconazole for onychomycosis at any of the tested doses.