Jie Ding, Qian Zhang, Qin Yang, Qin Zhang, Sihui Tu, Yangyang Zuo, Zhiwei Yao, Peng Deng, Lin Tao, Liang Zheng, Hu Wei
{"title":"新型选择性S1P1受体调节剂HE009的药代动力学、药效学和安全性研究","authors":"Jie Ding, Qian Zhang, Qin Yang, Qin Zhang, Sihui Tu, Yangyang Zuo, Zhiwei Yao, Peng Deng, Lin Tao, Liang Zheng, Hu Wei","doi":"10.1080/13543784.2025.2570244","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>HE009,a novel selective sphingosine-1-phosphate receptor-1(S1P1) modulator, was evaluated in healthy Chinese subjects to assess itspharmacokinetics, pharmacodynamics, and safety profile.</p><p><strong>Research design and methods: </strong>This randomized, placebo-controlled phase I studycomprised single ascending dose (SAD, 0.05-4.0 mg), multiple ascending dose(MAD, 0.5-3.0 mg), dose titration, and food effect components.</p><p><strong>Results: </strong>HE009 exhibited dose-proportional exposure, with T<sub>max</sub>of 4-6 hours and t<sub>1/2</sub> of 16-24 hours, supporting once-daily dosing.Steady-state was achieved by day 7 with minimal accumulation (1.7-2.0 fold). Aclear concentration-effect relationship was observed, with maximum lymphocytecount reductions of 58% (SAD) and 70-80% (MAD). Notably, HE009 demonstrated afavorable cardiac safety profile, with transient, asymptomatic bradycardiamitigated by dose titration. No events related to hypertension were observedduring the study period.</p><p><strong>Conclusion: </strong>Thesefindings suggest HE009 offers potential advantages in efficacy, safety, anddosing flexibility compared to existing S1P receptor modulators for treatingautoimmune disorders like systemic lupus erythematosus.</p><p><strong>Trial registration: </strong>The trial was registered on the ChineseClinical Trial Registry, (Identifier No. ChiCTR2200066345), Registered December1, 2022.</p>","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":""},"PeriodicalIF":4.1000,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Pharmacokinetics, pharmacodynamics, and safety of HE009, a novel selective S1P1 receptor modulator, in healthy Chinese subjects.\",\"authors\":\"Jie Ding, Qian Zhang, Qin Yang, Qin Zhang, Sihui Tu, Yangyang Zuo, Zhiwei Yao, Peng Deng, Lin Tao, Liang Zheng, Hu Wei\",\"doi\":\"10.1080/13543784.2025.2570244\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>HE009,a novel selective sphingosine-1-phosphate receptor-1(S1P1) modulator, was evaluated in healthy Chinese subjects to assess itspharmacokinetics, pharmacodynamics, and safety profile.</p><p><strong>Research design and methods: </strong>This randomized, placebo-controlled phase I studycomprised single ascending dose (SAD, 0.05-4.0 mg), multiple ascending dose(MAD, 0.5-3.0 mg), dose titration, and food effect components.</p><p><strong>Results: </strong>HE009 exhibited dose-proportional exposure, with T<sub>max</sub>of 4-6 hours and t<sub>1/2</sub> of 16-24 hours, supporting once-daily dosing.Steady-state was achieved by day 7 with minimal accumulation (1.7-2.0 fold). Aclear concentration-effect relationship was observed, with maximum lymphocytecount reductions of 58% (SAD) and 70-80% (MAD). Notably, HE009 demonstrated afavorable cardiac safety profile, with transient, asymptomatic bradycardiamitigated by dose titration. No events related to hypertension were observedduring the study period.</p><p><strong>Conclusion: </strong>Thesefindings suggest HE009 offers potential advantages in efficacy, safety, anddosing flexibility compared to existing S1P receptor modulators for treatingautoimmune disorders like systemic lupus erythematosus.</p><p><strong>Trial registration: </strong>The trial was registered on the ChineseClinical Trial Registry, (Identifier No. ChiCTR2200066345), Registered December1, 2022.</p>\",\"PeriodicalId\":12313,\"journal\":{\"name\":\"Expert opinion on investigational drugs\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2025-10-06\",\"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/10.1080/13543784.2025.2570244\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert opinion on investigational drugs","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/13543784.2025.2570244","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Pharmacokinetics, pharmacodynamics, and safety of HE009, a novel selective S1P1 receptor modulator, in healthy Chinese subjects.
Objective: HE009,a novel selective sphingosine-1-phosphate receptor-1(S1P1) modulator, was evaluated in healthy Chinese subjects to assess itspharmacokinetics, pharmacodynamics, and safety profile.
Research design and methods: This randomized, placebo-controlled phase I studycomprised single ascending dose (SAD, 0.05-4.0 mg), multiple ascending dose(MAD, 0.5-3.0 mg), dose titration, and food effect components.
Results: HE009 exhibited dose-proportional exposure, with Tmaxof 4-6 hours and t1/2 of 16-24 hours, supporting once-daily dosing.Steady-state was achieved by day 7 with minimal accumulation (1.7-2.0 fold). Aclear concentration-effect relationship was observed, with maximum lymphocytecount reductions of 58% (SAD) and 70-80% (MAD). Notably, HE009 demonstrated afavorable cardiac safety profile, with transient, asymptomatic bradycardiamitigated by dose titration. No events related to hypertension were observedduring the study period.
Conclusion: Thesefindings suggest HE009 offers potential advantages in efficacy, safety, anddosing flexibility compared to existing S1P receptor modulators for treatingautoimmune disorders like systemic lupus erythematosus.
Trial registration: The trial was registered on the ChineseClinical Trial Registry, (Identifier No. ChiCTR2200066345), Registered December1, 2022.
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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