Phase I Clinical Research Center, Huashan Hospital, Fudan University, Shanghai, China.
Pharmaceutical Sciences, Roche Innovation Center Shanghai, Shanghai, China.
Clin Transl Sci. 2022 Jan;15(1):195-203. doi: 10.1111/cts.13134. Epub 2021 Sep 25.
The objectives of this phase I study are to assess the safety, tolerability, and pharmacokinetics (PKs) of RO7049389 in healthy Chinese volunteers (HVs) and evaluate potential ethnic differences in the safety and PKs using data from this study and the first-in-human study (in which most of the HVs were non-Asian). HVs randomly received a single dose of 200-600 mg of RO7049389 or a placebo in a single ascending dose (n = 28) or multiple doses of 200-400 mg of RO7049389 or a placebo in multiple ascending doses (n = 24). Safety and tolerability were monitored throughout the study. Serial blood samples were collected for PK analysis. RO7049389 was safe and well-tolerated in the HVs. The time to maximum concentration ranged from 1.5 to 3.0 h, and terminal half-life ranged from 3.66 to 14.6 h. A single dose of 200-600 mg and multiple doses of 200-400 mg exhibited nonlinear PKs. In general, the safety profiles were comparable between non-Asian and Asian HVs, but the plasma exposure of RO7049389 in Chinese HVs was higher than that in non-Asian HVs. The data generated from this study will provide guidance for future clinical studies on RO7049389 in Chinese/Asian patients with hepatitis B virus.
这项 I 期研究的目的是评估 RO7049389 在健康中国志愿者（HV）中的安全性、耐受性和药代动力学（PKs），并使用来自这项研究和首次人体研究（其中大多数 HV 是非亚洲人）的数据评估安全性和 PKs 中的潜在种族差异。HV 随机接受单剂量 200-600mg 的 RO7049389 或安慰剂（n=28），或多剂量 200-400mg 的 RO7049389 或安慰剂（n=24）。在整个研究过程中监测安全性和耐受性。采集连续血样进行 PK 分析。RO7049389 在 HV 中安全且耐受良好。最大浓度时间范围为 1.5 至 3.0 小时，终末半衰期范围为 3.66 至 14.6 小时。单剂量 200-600mg 和多剂量 200-400mg 表现出非线性 PKs。一般来说，非亚洲和亚洲 HV 之间的安全性概况相当，但中国 HV 中 RO7049389 的血浆暴露量高于非亚洲 HV。这项研究产生的数据将为未来在中国/亚洲乙型肝炎病毒患者中进行 RO7049389 临床研究提供指导。
