Washington University School of Medicine, St Louis, MO, USA.
Mercury Street Medical, Butte, MT, USA.
J Antimicrob Chemother. 2019 Oct 1;74(10):3056-3062. doi: 10.1093/jac/dkz277.
To evaluate the safety and efficacy of two dosing regimens of oral ibrexafungerp (formerly SCY-078), a novel orally bioavailable β-glucan synthase inhibitor, in subjects with invasive candidiasis versus the standard of care (SOC) and to identify the dose to achieve target exposure (15.4 μM·h) in >80% of the intended population.
In a multinational, open-label study, patients with documented invasive candidiasis were randomized to receive step-down therapy to one of three treatment arms: two dosing regimens of novel oral ibrexafungerp or the SOC treatment following initial echinocandin therapy. Plasma samples were collected to evaluate exposure by population pharmacokinetic (PK) modelling. Safety was assessed throughout the study and global response at the end of treatment.
Out of 27 subjects enrolled, 7 received ibrexafungerp 500 mg, 7 received ibrexafungerp 750 mg and 8 received the SOC. Five did not meet criteria for randomization. Population PK analysis indicated that an ibrexafungerp 750 mg regimen is predicted to achieve the target exposure in ∼85% of the population. The rate of adverse events was similar among patients receiving ibrexafungerp or fluconazole. Similar favourable response rates were reported among all groups: 86% (n = 6) in the ibrexafungerp 750 mg versus 71% (n = 5) in both the fluconazole and ibrexafungerp 500 mg treatment arms. The one subject treated with continued micafungin had a favourable global response.
The oral ibrexafungerp dose estimated to achieve the target exposure in subjects with invasive candidiasis is 750 mg daily. This dose was well tolerated and achieved a favourable global response rate, similar to the SOC.
评估新型口服β-葡聚糖合酶抑制剂艾沙康唑（前称 SCY-078）两种给药方案在侵袭性念珠菌病患者中的安全性和疗效，与标准治疗（SOC）相比，并确定实现目标暴露（15.4μM·h）的剂量在>80%的目标人群中。
在一项多中心、开放性研究中，经证实患有侵袭性念珠菌病的患者被随机分配接受逐步降阶梯治疗，进入以下三个治疗组之一：两种新型口服艾沙康唑给药方案或初始棘白菌素治疗后的 SOC 治疗。采集血浆样本进行群体药代动力学（PK）建模以评估暴露情况。在整个研究过程中评估安全性，并在治疗结束时评估总体反应。
27 例入组患者中，7 例接受艾沙康唑 500mg，7 例接受艾沙康唑 750mg，8 例接受 SOC。5 例不符合随机分组标准。群体 PK 分析表明，艾沙康唑 750mg 方案预计将在约 85%的人群中达到目标暴露。接受艾沙康唑或氟康唑的患者的不良事件发生率相似。所有组均报告了相似的有利反应率：艾沙康唑 750mg 组 86%（n=6），氟康唑和艾沙康唑 500mg 组均为 71%（n=5）。接受继续米卡芬净治疗的 1 例患者有良好的总体反应。
在侵袭性念珠菌病患者中估计达到目标暴露的艾沙康唑口服剂量为每天 750mg。该剂量耐受性良好，实现了与 SOC 相似的有利全球反应率。
