{"title":"新型atp -柠檬酸裂解酶抑制剂BGT-002在中国健康受试者体内的安全性、耐受性和药代动力学的I期研究","authors":"Yun Liu, Chengyin Yu, Yifan Zhang, Zhifu Xie, Yating Wang, Hongjie Qian, Liyu Liang, Yanmei Liu, Qian Chen, Jingying Jia, Sai Yan, Xiaoyin Lai, Wei Li, Jingya Li, Yangming Zhang, Fajun Nan, Chen Yu","doi":"10.2147/DDDT.S504814","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>This Phase I study evaluated the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of BGT-002, a novel ATP-citrate lyase (ACLY) inhibitor, in healthy Chinese adults.</p><p><strong>Methods: </strong>This study included three parts: Part I (single-ascending-dose study), Part II (multiple-ascending-dose study), and Part III (food effect study). A total of 104 healthy subjects were enrolled in the study and were given BGT-002 tablet or placebo per protocol requirements. Blood samples were collected for pharmacokinetic and pharmacodynamic analysis. Safety was assessed by clinical examinations and adverse events.</p><p><strong>Results: </strong>In Part I, BGT-002 demonstrated rapid absorption with a T<sub>max</sub> of 0.67 to 1.75 hours, and slow elimination with a T<sub>1/2</sub> of 24.53 to 72.86 hours, prolonged with increased dosages. C<sub>max</sub> and AUC<sub>0-∞</sub> ranged from 1.55 to 48.39 μg/mL, and 31.09 to 2930.69 h·μg/mL, respectively. In Part II, the accumulation index (Rac) of C<sub>max</sub> and AUC<sub>tau</sub> following 14 days of consecutive administration were 3.53 to 3.62 and 5.29 to 5.59, respectively, with a dose-proportionality PK profile. The levels of total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C), and low-density lipoprotein cholesterol (LDL-C) were maximally decreased by 15.80%, 18.50%, and 22.37%, respectively. In Part III, the geometric mean ratio (90% CI) of fed to fasting condition in C<sub>max</sub> and AUC<sub>0-∞</sub> of BGT-002 were 73.11% and 98.36%, respectively, indicating a minor food effect on the absorption rate. Across the study, two cases of Grade 3 adverse events (elevated blood triglycerides) were reported, both of which were assessed as not related to BGT-002. No serious adverse events were observed.</p><p><strong>Conclusion: </strong>BGT-002 demonstrated favorable safety, tolerability, and lipid-lowering effects, supporting its potential for further clinical development.</p><p><strong>Clinical trial registration: </strong>ChiCTR2200057793(https://www.chictr.org.cn/showproj.html?proj=160210); ChiCTR2300067474(https://www.chictr.org.cn/showproj.html?proj=182183); ChiCTR2300067472(https://www.chictr.org.cn/showproj.html?proj=184079).</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"1783-1794"},"PeriodicalIF":6.1000,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910062/pdf/","citationCount":"0","resultStr":"{\"title\":\"A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics of BGT-002, a Novel ATP-Citrate Lyase Inhibitor, in Healthy Chinese Subjects.\",\"authors\":\"Yun Liu, Chengyin Yu, Yifan Zhang, Zhifu Xie, Yating Wang, Hongjie Qian, Liyu Liang, Yanmei Liu, Qian Chen, Jingying Jia, Sai Yan, Xiaoyin Lai, Wei Li, Jingya Li, Yangming Zhang, Fajun Nan, Chen Yu\",\"doi\":\"10.2147/DDDT.S504814\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>This Phase I study evaluated the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of BGT-002, a novel ATP-citrate lyase (ACLY) inhibitor, in healthy Chinese adults.</p><p><strong>Methods: </strong>This study included three parts: Part I (single-ascending-dose study), Part II (multiple-ascending-dose study), and Part III (food effect study). A total of 104 healthy subjects were enrolled in the study and were given BGT-002 tablet or placebo per protocol requirements. Blood samples were collected for pharmacokinetic and pharmacodynamic analysis. Safety was assessed by clinical examinations and adverse events.</p><p><strong>Results: </strong>In Part I, BGT-002 demonstrated rapid absorption with a T<sub>max</sub> of 0.67 to 1.75 hours, and slow elimination with a T<sub>1/2</sub> of 24.53 to 72.86 hours, prolonged with increased dosages. C<sub>max</sub> and AUC<sub>0-∞</sub> ranged from 1.55 to 48.39 μg/mL, and 31.09 to 2930.69 h·μg/mL, respectively. In Part II, the accumulation index (Rac) of C<sub>max</sub> and AUC<sub>tau</sub> following 14 days of consecutive administration were 3.53 to 3.62 and 5.29 to 5.59, respectively, with a dose-proportionality PK profile. The levels of total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C), and low-density lipoprotein cholesterol (LDL-C) were maximally decreased by 15.80%, 18.50%, and 22.37%, respectively. In Part III, the geometric mean ratio (90% CI) of fed to fasting condition in C<sub>max</sub> and AUC<sub>0-∞</sub> of BGT-002 were 73.11% and 98.36%, respectively, indicating a minor food effect on the absorption rate. Across the study, two cases of Grade 3 adverse events (elevated blood triglycerides) were reported, both of which were assessed as not related to BGT-002. No serious adverse events were observed.</p><p><strong>Conclusion: </strong>BGT-002 demonstrated favorable safety, tolerability, and lipid-lowering effects, supporting its potential for further clinical development.</p><p><strong>Clinical trial registration: </strong>ChiCTR2200057793(https://www.chictr.org.cn/showproj.html?proj=160210); ChiCTR2300067474(https://www.chictr.org.cn/showproj.html?proj=182183); ChiCTR2300067472(https://www.chictr.org.cn/showproj.html?proj=184079).</p>\",\"PeriodicalId\":11290,\"journal\":{\"name\":\"Drug Design, Development and Therapy\",\"volume\":\"19 \",\"pages\":\"1783-1794\"},\"PeriodicalIF\":6.1000,\"publicationDate\":\"2025-03-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910062/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Drug Design, Development and Therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2147/DDDT.S504814\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Design, Development and Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/DDDT.S504814","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics of BGT-002, a Novel ATP-Citrate Lyase Inhibitor, in Healthy Chinese Subjects.
Objective: This Phase I study evaluated the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of BGT-002, a novel ATP-citrate lyase (ACLY) inhibitor, in healthy Chinese adults.
Methods: This study included three parts: Part I (single-ascending-dose study), Part II (multiple-ascending-dose study), and Part III (food effect study). A total of 104 healthy subjects were enrolled in the study and were given BGT-002 tablet or placebo per protocol requirements. Blood samples were collected for pharmacokinetic and pharmacodynamic analysis. Safety was assessed by clinical examinations and adverse events.
Results: In Part I, BGT-002 demonstrated rapid absorption with a Tmax of 0.67 to 1.75 hours, and slow elimination with a T1/2 of 24.53 to 72.86 hours, prolonged with increased dosages. Cmax and AUC0-∞ ranged from 1.55 to 48.39 μg/mL, and 31.09 to 2930.69 h·μg/mL, respectively. In Part II, the accumulation index (Rac) of Cmax and AUCtau following 14 days of consecutive administration were 3.53 to 3.62 and 5.29 to 5.59, respectively, with a dose-proportionality PK profile. The levels of total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C), and low-density lipoprotein cholesterol (LDL-C) were maximally decreased by 15.80%, 18.50%, and 22.37%, respectively. In Part III, the geometric mean ratio (90% CI) of fed to fasting condition in Cmax and AUC0-∞ of BGT-002 were 73.11% and 98.36%, respectively, indicating a minor food effect on the absorption rate. Across the study, two cases of Grade 3 adverse events (elevated blood triglycerides) were reported, both of which were assessed as not related to BGT-002. No serious adverse events were observed.
Conclusion: BGT-002 demonstrated favorable safety, tolerability, and lipid-lowering effects, supporting its potential for further clinical development.
期刊介绍：
Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications.
The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas.
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Mechanisms of action and signalling pathways
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Gene therapy, cell therapy and immunotherapy
Personalized medicine and pharmacogenomics
Clinical drug evaluation
Patient safety and sustained use of medicines.
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