School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi, South Korea.
Qurient Co., Ltd., Seongnam, Gyeonggi, South Korea.
Antimicrob Agents Chemother. 2022 Jan 18;66(1):e0143621. doi: 10.1128/AAC.01436-21. Epub 2021 Oct 25.
Telacebec (Q203) is a potent drug candidate under clinical development for the treatment of drug-naïve and drug-resistant tuberculosis. The first-in-human randomized, placebo-controlled, double-blind, dose-escalation Phase 1A trial (Q203-TB-PI-US001) was conducted to evaluate the safety, tolerability, and pharmacokinetics of telacebec. A total of 56 normal, healthy, male and female subjects (42 active and 14 placebo) were enrolled in the study. The doses of telacebec were 10 mg (Cohort 1), 30 mg (Cohort 2), 50 mg (Cohort 3), 100 mg (Cohort 4), 200 mg (Cohort 5), 400 mg (Cohort 6), and 800 mg (Cohort 7) in a fasted state. Subjects participating in Cohort 4 were also enrolled in Cohort 8 to investigate the food effect on the pharmacokinetics of telacebec after a high-fat meal. In all subjects dosed with telacebec (10 to 800 mg), telacebec was well tolerated and did not lead to any significant or serious adverse events. Following a single oral administration of telacebec (10 to 800 mg), telacebec plasma concentration reached the maximal plasma concentration () in average 2.0 to 3.5 h and showed multi-exponential decline thereafter. The area under the plasma concentration versus time curve (AUC) was approximately dose-proportional. A significant increase in plasma concentrations was observed in the fed condition compared with the fasted condition with the geometric mean ratio of 3.93 for . Moderate delay in (4.5 h) was also observed in the fed condition. These results, combined with the demonstrated activity against drug-sensitive and multidrug-resistant Mycobacterium tuberculosis, support further investigation of telacebec for the treatment of tuberculosis.
特拉克贝（Q203）是一种在研的强效药物候选物，用于治疗初治和耐药结核病。进行了首例人体随机、安慰剂对照、双盲、剂量递增的 1A 期临床试验（Q203-TB-PI-US001），以评估特拉克贝的安全性、耐受性和药代动力学。共有 56 名健康的男性和女性（42 名活性药物组和 14 名安慰剂组）参与了该研究。特拉克贝的剂量为 10mg（队列 1）、30mg（队列 2）、50mg（队列 3）、100mg（队列 4）、200mg（队列 5）、400mg（队列 6）和 800mg（队列 7），均在禁食状态下给药。参加队列 4 的受试者还参加了队列 8，以研究高脂肪餐后特拉克贝的药代动力学受食物影响的情况。所有接受特拉克贝（10 至 800mg）治疗的受试者中，特拉克贝均具有良好的耐受性，不会导致任何显著或严重的不良事件。单次口服特拉克贝（10 至 800mg）后，特拉克贝平均在 2.0 至 3.5 小时达到最大血浆浓度（），此后呈多指数下降。血浆浓度-时间曲线下面积（AUC）与剂量大致呈比例。与禁食状态相比，在进食状态下观察到血浆浓度显著增加，几何均数比值为 3.93。在进食状态下也观察到 （4.5 小时）中度延迟。这些结果，加上对敏感和耐多药结核分枝杆菌的活性，支持进一步研究特拉克贝治疗结核病。
