Phase 1 trials of BI 764198, a transient receptor potential channel 6 inhibitor, in healthy volunteers and participants with kidney impairment.

IF 4.1 2区医学 Q1 PHARMACOLOGY & PHARMACY

Expert opinion on investigational drugs Pub Date : 2025-05-01 Epub Date: 2025-06-08 DOI:10.1080/13543784.2025.2510673

Armin Schultz, Atef Halabi, Friedeborg Seitz, Katrien Lemmens, Hauke S Wülfrath, Maximilian T Lobmeyer, Silke Retlich, Wansuk Choi, Nima Soleymanlou

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引用次数: 0

Abstract

Background: BI 764198 could reduce podocyte injury in focal segmental glomerulosclerosis (FSGS).

Research design and methods: Four Phase 1 BI 764198 trials: single rising dose (SRD) and multiple rising dose (MRD)/drug-drug interaction trials in healthy volunteers; relative bioavailability (rBA) study (food and formulations effects on pharmacokinetics; PK); and kidney impairment (KI) PK study.

Results: SRD trial: 4/54 BI 764198-treated participants (7.4%) had ≥ 1 investigator-defined drug-related adverse event (DRAE): headache (n = 3; 5.6%); diarrhea (n = 1; 16.7%). BI 764198 PK was approximately linear. MRD trial: DRAEs occurred in 5/32 (15.6%) participants receiving BI 764198 and 1/8 (12.5%) receiving placebo. Once-daily BI 764198 80 mg (10 days) did not alter midazolam PK. All BI 764198 formulations tested had similar rBA; food did not affect PK. KI study: geometric mean ratios for area under the plasma concentration-time curve were 147.8% and 177.7% for participants with moderate and severe KI, respectively (vs. without). Limitations include typically small Phase 1 sample sizes and open-label design for the rBA and KI trials.

Conclusions: BI 764198 was well tolerated and could be taken with/without food; evaluation in FSGS is ongoing.

Clinical trial registration: The trials are registered at www.clinicaltrials.gov with codes NCT03854552; NCT04102462; NCT04656288; NCT04176536.

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BI 764198是一种瞬时受体电位通道6抑制剂，在健康志愿者和肾损害患者中进行一期试验。

背景：BI 764198可减轻局灶节段性肾小球硬化（FSGS）足细胞损伤。研究设计和方法：四项i期BI 764198试验：健康志愿者单次上升剂量（SRD）和多次上升剂量(MRD)/药物-药物相互作用试验；相对生物利用度（rBA）研究（食品和制剂对药代动力学的影响）；PK);和肾损害（KI） PK研究。结果：SRD试验：4/54 BI 764198治疗的参与者（7.4%）有≥1个研究者定义的药物相关不良事件（DRAE）：头痛(n = 3；5.6%);腹泻(n = 1；16.7%)。在剂量≥10 mg时，BI 764198 PK近似线性。MRD试验：接受BI 764198的受试者中有5/32（15.6%）发生DRAEs，接受安慰剂的受试者中有1/8（12.5%）发生DRAEs。每日一次BI 764198 80 mg（10天）不改变咪达唑仑PK。所有测试的BI 764198配方的rBA相似；食物不影响PK。KI研究：中度和重度KI受试者的血药浓度-时间曲线下面积的几何平均比分别为147.8%和177.7%（与无KI的受试者相比）。rBA和KI试验的局限性包括典型的小一期样本量和开放标签设计。结论：BI 764198耐受性良好，可伴餐或不伴餐服用；FSGS评估正在进行中。临床试验注册：在www.clinicaltrials.gov注册，代码为NCT03854552；NCT04102462;NCT04656288;NCT04176536。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.