RO7049389在中国健康志愿者中的安全性、耐受性和药代动力学

StephenW

RO7049389在中国健康志愿者中的安全性、耐受性和药代动力学评价

吴小杰1、盛峰2、张静1、张文宏3、张雨辰2、朱明芬4、Miriam Triyatni 5、赵娜6、青岩博4、金玉燕2

隶属关系隶属关系    1    中国上海复旦大学华山医院I期临床研究中心。    2    制药科学，上海罗氏创新中心，上海，中国。    3    中国上海复旦大学华山医院感染科。    4    I2O DTA，上海罗氏创新中心，上海，中国。    5    早期开发安全，罗氏制药，巴塞尔，瑞士。    6    生物统计学，罗氏制药产品开发上海，上海，中国。

PMID：34562067 DOI：10.1111/cts.13134

抽象:
本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 (PK)，并使用本研究和首个研究数据评估安全性和 PK 的潜在种族差异。人类研究（其中大多数 HV 是非亚洲人）。 HV 随机接受单剂量 200-600 毫克 RO7049389 或安慰剂（n = 28）或多剂量 200-400 mg RO7049389 或安慰剂（n = 24）。在整个研究过程中监测安全性和耐受性。收集系列血样用于PK分析。 RO7049389 在 HV 中是安全且耐受良好的。达到最大浓度的时间为 1.5 至 3.0 小时，终末半衰期为 3.66 至 14.6 小时。 200-600 mg 的单剂量和 200-400 mg 的多剂量表现出非线性 PK。总的来说，非亚洲和亚洲 HV 的安全性特征相当，但中国 HV 中 RO7049389 的血浆暴露量高于非亚洲 HV。本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 的临床研究提供指导。© 2021 罗氏中国研发中心有限公司。《临床与转化科学》由 Wiley Periodicals LLC 代表美国临床药理学与治疗学会出版。

StephenW

Evaluation of the safety, tolerability, and pharmacokinetics of RO7049389 in healthy Chinese volunteers
Xiaojie Wu  1 , Sheng Feng  2 , Jing Zhang  1 , Wenhong Zhang  3 , Yuchen Zhang  2 , Mingfen Zhu  4 , Miriam Triyatni  5 , Na Zhao  6 , Qingyan Bo  4 , Yuyan Jin  2
Affiliations
Affiliations

    1
    Phase I Clinical Research Center, Huashan Hospital, Fudan University, Shanghai, China.
    2
    Pharmaceutical Sciences, Roche Innovation Center Shanghai, Shanghai, China.
    3
    Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
    4
    I2O DTA, Roche Innovation Center Shanghai, Shanghai, China.
    5
    Early Development Safety, Roche Pharma, Basel, Switzerland.
    6
    Biostatistics, Roche Pharma Product Development Shanghai, Shanghai, China.

    PMID: 34562067 DOI: 10.1111/cts.13134

Abstract

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.

© 2021 Roche R&D Center China Ltd.Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.

StephenW

https://ascpt.onlinelibrary.wile ... t/10.1111/cts.13134