A randomized, Phase I study of the safety, tolerability, and pharmacokinetics of BI 764198, a transient receptor potential channel 6 (TRPC6) inhibitor, in healthy Japanese men.

IF 4.9 2区医学 Q1 PHARMACOLOGY & PHARMACY

Expert opinion on investigational drugs Pub Date : 2025-05-01 Epub Date: 2025-06-03 DOI:10.1080/13543784.2025.2510664

Takuma Yonemura, Akiko Sarashina, Yoshifumi Tachibana, Silke Retlich, Nima Soleymanlou

{"title":"A randomized, Phase I study of the safety, tolerability, and pharmacokinetics of BI 764198, a transient receptor potential channel 6 (TRPC6) inhibitor, in healthy Japanese men.","authors":"Takuma Yonemura, Akiko Sarashina, Yoshifumi Tachibana, Silke Retlich, Nima Soleymanlou","doi":"10.1080/13543784.2025.2510664","DOIUrl":null,"url":null,"abstract":"Background: BI 764198 is a selective, oral transient receptor potential cation channel, subfamily C, member 6 inhibitor under investigation for focal segmental glomerulosclerosis.Research design and methods: Phase I study in 44 Japanese male volunteers. Single dose part: BI 764198 20 mg (n = 6) vs. placebo (n = 2); multiple dose part: BI 764198 40, 80, or 160 mg (n = 9 each) or placebo (n = 9) as a single dose then multiple daily dosing for 2 weeks. Primary endpoint: participants with drug-related adverse events (DRAEs); secondary endpoints: pharmacokinetic.Results: DRAEs were reported in 20.5% (9/44) of participants (total BI 764198 21.2% [7/33]; placebo 18.2% [2/11]), mostly diarrhea (total BI 764198 15.2% [5/33]; placebo 18.2% [2/11]) and headache (BI 764198 80 mg 11.1% [1/9]; BI 764198 160 mg 33.3% [3/9]). BI 764198 exposure increased near dose proportionally to 80 mg and was slightly higher than anticipated with 160 mg. Pharmacokinetics were similar in Asians and non-Asians after accounting for body weight. Limitations include small sample size per dose and short trial duration.Conclusions: BI 764198 was well tolerated; exposure increased near dose proportionally to 80 mg, as previously observed in predominantly White volunteers.Clinical trial registration: This study was registered on Clinical Trials.gov, identifier NCT04665700.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"425-433"},"PeriodicalIF":4.9000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert opinion on investigational drugs","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/13543784.2025.2510664","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/6/3 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: BI 764198 is a selective, oral transient receptor potential cation channel, subfamily C, member 6 inhibitor under investigation for focal segmental glomerulosclerosis.

Research design and methods: Phase I study in 44 Japanese male volunteers. Single dose part: BI 764198 20 mg (n = 6) vs. placebo (n = 2); multiple dose part: BI 764198 40, 80, or 160 mg (n = 9 each) or placebo (n = 9) as a single dose then multiple daily dosing for 2 weeks. Primary endpoint: participants with drug-related adverse events (DRAEs); secondary endpoints: pharmacokinetic.

Results: DRAEs were reported in 20.5% (9/44) of participants (total BI 764198 21.2% [7/33]; placebo 18.2% [2/11]), mostly diarrhea (total BI 764198 15.2% [5/33]; placebo 18.2% [2/11]) and headache (BI 764198 80 mg 11.1% [1/9]; BI 764198 160 mg 33.3% [3/9]). BI 764198 exposure increased near dose proportionally to 80 mg and was slightly higher than anticipated with 160 mg. Pharmacokinetics were similar in Asians and non-Asians after accounting for body weight. Limitations include small sample size per dose and short trial duration.

Conclusions: BI 764198 was well tolerated; exposure increased near dose proportionally to 80 mg, as previously observed in predominantly White volunteers.

Clinical trial registration: This study was registered on Clinical Trials.gov, identifier NCT04665700.

查看原文本刊更多论文

BI 764198（一种瞬时受体电位通道6 （TRPC6）抑制剂）在日本健康男性中的安全性、耐受性和药代动力学的随机I期研究

背景：BI 764,198是一种选择性口服瞬时受体电位阳离子通道，亚家族C，成员6抑制剂，正在研究用于局灶节段性肾小球硬化。研究设计与方法：第一阶段研究对象为44名日本男性志愿者。单剂量部分：BI 764,198 20mg (n = 6) vs安慰剂（n = 2）；多剂量部分：BI 764,198 40,80或160 mg（每个n = 9）或安慰剂（n = 9）作为单次剂量，然后每天多次给药，持续2周。主要终点：有药物相关不良事件（DRAEs）的受试者；次要终点：药代动力学。结果：有20.5%（9/44）的参与者报告了DRAEs(总BI为764,198 21.2% [7/33]；安慰剂18.2%[2/11])，以腹泻为主(总BI 764,198 15.2% [5/33]；安慰剂18.2%[2/11])和头痛(BI 764,198 80 mg 11.1% [1/9]；BI 764,198 160 mg 33.3%[3/9])。BI 764198暴露接近剂量成比例增加至80毫克，略高于预期的160毫克。在考虑体重后，亚洲人和非亚洲人的药代动力学相似。局限性包括每次剂量的样本量小和试验时间短。结论：BI 764,198耐受性良好；暴露量几乎成比例地增加到80毫克，正如先前在白人志愿者中观察到的那样。临床试验注册：本研究已在Clinical Trials.gov注册，识别码NCT04665700。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Expert opinion on investigational drugs 医学-药学

CiteScore

10.00

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Expert Opinion on Investigational Drugs (ISSN 1354-3784 [print], 1744-7658 [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles and original papers on drugs in preclinical and early stage clinical development, providing expert opinion on the scope for future development. The Editors welcome: Reviews covering preclinical through to Phase II data on drugs or drug classes for specific indications, and their potential impact on future treatment strategies Drug Evaluations reviewing the clinical and pharmacological data on a particular drug Original Research papers reporting the results of clinical investigations on agents that are in Phase I and II clinical trials The audience consists of scientists, managers and decision-makers in the pharmaceutical industry, and others closely involved in R&D.