Abstract：
AWZ1066S has been developed as a potential treatment for the neglected tropical diseases lymphatic filariasis and onchocerciasis. AWZ1066S targets the Wolbachia bacterial endosymbiont present in the causative nematode parasites. This phase 1, first-in-human study aimed to assess the safety and pharmacokinetics of AWZ1066S in healthy human participants. In a randomized double-blind, placebo-controlled, single ascending dose study, healthy adults received a single oral dose of AWZ1066S (or placebo) and were followed up for 10 days. The planned single doses of AWZ1066S ranged from 100 to 1600 mg, and each dose was administered to a cohort of 8 participants (6 AWZ1066S and 2 placebo). In total 30 people participated, 18 (60%) female, median age 30.0 years (minimum 20, maximum 61). The cohorts administered 100, 200, 300, and 400 mg of AWZ1066S progressed unremarkably. After single 700-mg doses all 4 participants developed symptoms of acute gastritis and transient increases in liver enzymes. The severity of these adverse events ranged from mild to severe, with 1 participant needing hospital admission. Pharmacokinetic analysis indicated that AWZ1066S is rapidly absorbed with predictable pharmacokinetics. In conclusion, safety concerns prevented this study from reaching the human exposures needed for AWZ1066S to be clinically effective against lymphatic filariasis and onchocerciasis.
摘要：
AWZ1066S已被开发为被忽视的热带病淋巴丝虫病和盘尾丝虫病的潜在治疗方法。AWZ1066S靶向致病性线虫寄生虫中存在的Wolbachia细菌内共生体。这项第一阶段的首次人体研究旨在评估AWZ1066S在健康人类参与者中的安全性和药代动力学。在随机双盲中，安慰剂对照,单次递增剂量研究，健康成人接受单剂口服AWZ1066S(或安慰剂),随访10天.AWZ1066S的计划单剂量范围为100至1600mg，每个剂量给一组8名参与者（6名AWZ1066S和2名安慰剂）。共有30人参加，18（60％）女性，中位年龄30.0岁（最小20岁，最大61岁）。给予100、200、300和400mgAWZ1066S的队列进展不显著。单次700毫克剂量后，所有4名参与者均出现急性胃炎症状和肝酶短暂增加。这些不良事件的严重程度从轻度到重度，1名参与者需要住院。药代动力学分析表明AWZ1066S快速吸收,具有可预测的药代动力学。总之,由于安全性方面的考虑,本研究无法达到AWZ1066S对淋巴丝虫病和盘尾丝虫病临床有效所需的人体暴露量.
