RO7049389, an inhibitor of hepatitis B virus (HBV) capsid assembly, is being developed for the treatment of patients with chronic HBV infection. The objectives of this first-in-human study are to assess the safety, tolerability, pharmacokinetics (PK), food effect, inhibitory effect on CYP3A, and effect on QT of RO7049389 in healthy participants. Five components, single-ascending-dose (SAD) cohorts, multiple-ascending-dose (MAD) cohorts, food effect assessment, drug-drug interaction assessment, and concentration-QT analysis were integrated in one study (five-in-one). Participants randomly received a single dose of 150 to 2,500 mg RO7049389 or placebo in SAD cohorts (n = 41), or multiple doses of 200 to 800 mg RO7049389 or placebo in MAD cohorts (n = 42). A single doses of 450 mg RO7049389 was administered under fasted and fed condition. The microdose of midazolam was administered before and after multiple dosing of RO7049389. Safety and tolerability were monitored throughout the study. Serial blood and urine samples were collected for the PK analysis. RO7049389 was safe and well tolerated in healthy participants. Absorption and elimination of RO7049389 occurred rapidly in plasma with minimal recovery in urine. Greater than dose-proportional increases in plasma exposure were observed. Exposure of RO7049389 (450 mg) increased by ∼2-fold when administered with a high-fat meal. The inhibition effect of RO7049389 on CYP3A was weak (<20%). No effect on QT interval was observed at up to a single dose of 2,500 mg. RO7049389 displayed a favorable safety, tolerability and PK profile suitable for further clinical development. (This trial was registered at ClinicalTrials.gov with the identifier NCT02952924.)

中文翻译：

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一项五合一的首次人体研究，旨在评估 RO7049389（一种乙型肝炎病毒衣壳组装抑制剂）在健康参与者单次和多次递增剂量后的安全性、耐受性和药代动力学。

RO7049389 是一种乙型肝炎病毒 (HBV) 衣壳组装抑制剂，正在开发用于治疗慢性 HBV 感染患者。这项首次人体研究的目的是评估 RO7049389 在健康参与者中的安全性、耐受性、药代动力学 (PK)、食物效应、对 CYP3A 的抑制作用和对 QT 的影响。五个组成部分，单次递增剂量 (SAD) 队列、多次递增剂量 (MAD) 队列、食物效应评估、药物-药物相互作用评估和浓度-QT 分析整合在一项研究中（五合一） . 参与者在 SAD 队列中随机接受单剂量 150 至 2,500 mg RO7049389 或安慰剂（n = 41），或在 MAD 队列中接受多剂量 200 至 800 mg RO7049389 或安慰剂（n= 42)。在禁食和进食条件下给予单剂量 450 mg RO7049389。在多次给药 RO7049389 之前和之后给予咪达唑仑微剂量。在整个研究过程中监测安全性和耐受性。收集系列血液和尿液样本用于 PK 分析。RO7049389 在健康参与者中是安全且耐受性良好的。RO7049389 的吸收和消除在血浆中迅速发生，尿液中的恢复极少。观察到血浆暴露大于剂量比例增加。RO7049389 (450 mg) 的暴露量在与高脂肪餐一起服用时增加了约 2 倍。RO7049389对CYP3A的抑制作用较弱（<20%）。在高达 2,500 mg 的单剂量下未观察到对 QT 间期的影响。RO7049389 表现出良好的安全性，耐受性和 PK 曲线适用于进一步的临床开发。（该试验已在 ClinicalTrials.gov 注册，标识符为 NCT02952924。）