Armin Schultz, Atef Halabi, Friedeborg Seitz, Katrien Lemmens, Hauke S Wülfrath, Maximilian T Lobmeyer, Silke Retlich, Wansuk Choi, Nima Soleymanlou
{"title":"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。","authors":"Armin Schultz, Atef Halabi, Friedeborg Seitz, Katrien Lemmens, Hauke S Wülfrath, Maximilian T Lobmeyer, Silke Retlich, Wansuk Choi, Nima Soleymanlou","doi":"10.1080/13543784.2025.2510673","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>BI 764198 could reduce podocyte injury in focal segmental glomerulosclerosis (FSGS).</p><p><strong>Research design and methods: </strong>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.</p><p><strong>Results: </strong>SRD trial: 4/54 BI 764198-treated participants (7.4%) had ≥ 1 investigator-defined drug-related adverse event (DRAE): headache (<i>n</i> = 3; 5.6%); diarrhea (<i>n</i> = 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.</p><p><strong>Conclusions: </strong>BI 764198 was well tolerated and could be taken with/without food; evaluation in FSGS is ongoing.</p><p><strong>Clinical trial registration: </strong>The trials are registered at www.clinicaltrials.gov with codes NCT03854552; NCT04102462; NCT04656288; NCT04176536.</p>","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"415-423"},"PeriodicalIF":4.1000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Phase 1 trials of BI 764198, a transient receptor potential channel 6 inhibitor, in healthy volunteers and participants with kidney impairment.\",\"authors\":\"Armin Schultz, Atef Halabi, Friedeborg Seitz, Katrien Lemmens, Hauke S Wülfrath, Maximilian T Lobmeyer, Silke Retlich, Wansuk Choi, Nima Soleymanlou\",\"doi\":\"10.1080/13543784.2025.2510673\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>BI 764198 could reduce podocyte injury in focal segmental glomerulosclerosis (FSGS).</p><p><strong>Research design and methods: </strong>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.</p><p><strong>Results: </strong>SRD trial: 4/54 BI 764198-treated participants (7.4%) had ≥ 1 investigator-defined drug-related adverse event (DRAE): headache (<i>n</i> = 3; 5.6%); diarrhea (<i>n</i> = 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). 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Phase 1 trials of BI 764198, a transient receptor potential channel 6 inhibitor, in healthy volunteers and participants with kidney impairment.
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.
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.
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