A phase I study to evaluate the safety, tolerability, and pharmacokinetics of HEC113995PA·H2O, a novel dual-acting serotonergic antidepressant, in healthy subjects
PurposeHEC113995PA·H2O is a novel, potent and selective serotonin (5-HT) reuptake inhibitor and a 5-HT1A receptor partial agonist, and thus is categorized as a serotonin partial agonist-reuptake inhibitor. The objective of this study was to evaluate the safety, tolerability, and pharmacokinetics of...
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Frontiers Media S.A.
2025-03-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1500974/full |
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| author | Xue Wu Xue Wu Xue Wu Qingqing Wu Qingqing Wu Qingqing Wu Qichen Ding Qichen Ding Qichen Ding Yulei Zhuang Lin Luo Yingjun Zhang Li Deng Chuanfei Jin Xue Li Zhangma Huang Haiping Qin Liang Xin Liang Xin Liang Xin Qian Chen Qian Chen Qian Chen Jingying Jia Jingying Jia Jingying Jia Yanmei Liu Yanmei Liu Yanmei Liu |
| author_facet | Xue Wu Xue Wu Xue Wu Qingqing Wu Qingqing Wu Qingqing Wu Qichen Ding Qichen Ding Qichen Ding Yulei Zhuang Lin Luo Yingjun Zhang Li Deng Chuanfei Jin Xue Li Zhangma Huang Haiping Qin Liang Xin Liang Xin Liang Xin Qian Chen Qian Chen Qian Chen Jingying Jia Jingying Jia Jingying Jia Yanmei Liu Yanmei Liu Yanmei Liu |
| author_sort | Xue Wu |
| collection | DOAJ |
| description | PurposeHEC113995PA·H2O is a novel, potent and selective serotonin (5-HT) reuptake inhibitor and a 5-HT1A receptor partial agonist, and thus is categorized as a serotonin partial agonist-reuptake inhibitor. The objective of this study was to evaluate the safety, tolerability, and pharmacokinetics of HEC113995PA·H2O in healthy subjects after single and multiple dosing, as well as the food effect on pharmacokinetics and safety of HEC113995PA·H2O.MethodsThe entire study was comprised of three parts: Part I (single ascending-dose study), Part II (food effect study), and Part III (multiple ascending-dose study). A total of 121 healthy subjects were enrolled in the study. HEC113995PA·H2O tablet or placebo was administered per protocol requirements. Blood samples were collected at the designated time points for pharmacokinetic analysis. Safety was assessed by clinical examinations and adverse events.ResultsIn Part I, AUC and Cmax were found to by and large linear within the 2.5–80 mg dose range. t1/2 of HEC113995PA·H2O was 27.17∼38.58 h. In Part II, we revealed that HEC113995PA·H2O administration post meal could increase Cmax and AUC0-t. In Part III, multiple administration led to accumulated body exposure and the PK of healthy subjects reached a steady state after 7 days of continuous administration in each dose group.ConclusionHEC113995PA·H2O was safe and generally well-tolerated in healthy subjects. Based on the pharmacokinetic and safety data mentioned above, we expect that postprandial administration will favorably increase drug concentrations in the body and reduce gastrointestinal adverse events. |
| format | Article |
| id | doaj-art-879e45f98d974ecfa84e849bd86b0cdc |
| institution | DOAJ |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-879e45f98d974ecfa84e849bd86b0cdc2025-08-20T02:40:48ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-03-011610.3389/fphar.2025.15009741500974A phase I study to evaluate the safety, tolerability, and pharmacokinetics of HEC113995PA·H2O, a novel dual-acting serotonergic antidepressant, in healthy subjectsXue Wu0Xue Wu1Xue Wu2Qingqing Wu3Qingqing Wu4Qingqing Wu5Qichen Ding6Qichen Ding7Qichen Ding8Yulei Zhuang9Lin Luo10Yingjun Zhang11Li Deng12Chuanfei Jin13Xue Li14Zhangma Huang15Haiping Qin16Liang Xin17Liang Xin18Liang Xin19Qian Chen20Qian Chen21Qian Chen22Jingying Jia23Jingying Jia24Jingying Jia25Yanmei Liu26Yanmei Liu27Yanmei Liu28Drug Clinical Trial Center, Shanghai Xuhui Central Hospital, Shanghai, ChinaShanghai Engineering Research Center of Phase I Clinical Research & Quality Consistency Evaluation for Drugs, Shanghai, ChinaShanghai Institute of Clinical Mass Spectrometry, Shanghai, ChinaDrug Clinical Trial Center, Shanghai Xuhui Central Hospital, Shanghai, ChinaShanghai Engineering Research Center of Phase I Clinical Research & Quality Consistency Evaluation for Drugs, Shanghai, ChinaShanghai Institute of Clinical Mass Spectrometry, Shanghai, ChinaDrug Clinical Trial Center, Shanghai Xuhui Central Hospital, Shanghai, ChinaShanghai Engineering Research Center of Phase I Clinical Research & Quality Consistency Evaluation for Drugs, Shanghai, ChinaShanghai Institute of Clinical Mass Spectrometry, Shanghai, ChinaSunshine Lake Pharma Co., LTD., Guangdong, ChinaSunshine Lake Pharma Co., LTD., Guangdong, ChinaSunshine Lake Pharma Co., LTD., Guangdong, ChinaSunshine Lake Pharma Co., LTD., Guangdong, ChinaSunshine Lake Pharma Co., LTD., Guangdong, ChinaSunshine Lake Pharma Co., LTD., Guangdong, ChinaSunshine Lake Pharma Co., LTD., Guangdong, ChinaED (Emergency Department) Emergency Ward, Shanghai Xuhui Central Hospital, Shanghai, ChinaDrug Clinical Trial Center, Shanghai Xuhui Central Hospital, Shanghai, ChinaShanghai Engineering Research Center of Phase I Clinical Research & Quality Consistency Evaluation for Drugs, Shanghai, ChinaShanghai Institute of Clinical Mass Spectrometry, Shanghai, ChinaDrug Clinical Trial Center, Shanghai Xuhui Central Hospital, Shanghai, ChinaShanghai Engineering Research Center of Phase I Clinical Research & Quality Consistency Evaluation for Drugs, Shanghai, ChinaShanghai Institute of Clinical Mass Spectrometry, Shanghai, ChinaDrug Clinical Trial Center, Shanghai Xuhui Central Hospital, Shanghai, ChinaShanghai Engineering Research Center of Phase I Clinical Research & Quality Consistency Evaluation for Drugs, Shanghai, ChinaShanghai Institute of Clinical Mass Spectrometry, Shanghai, ChinaDrug Clinical Trial Center, Shanghai Xuhui Central Hospital, Shanghai, ChinaShanghai Engineering Research Center of Phase I Clinical Research & Quality Consistency Evaluation for Drugs, Shanghai, ChinaShanghai Institute of Clinical Mass Spectrometry, Shanghai, ChinaPurposeHEC113995PA·H2O is a novel, potent and selective serotonin (5-HT) reuptake inhibitor and a 5-HT1A receptor partial agonist, and thus is categorized as a serotonin partial agonist-reuptake inhibitor. The objective of this study was to evaluate the safety, tolerability, and pharmacokinetics of HEC113995PA·H2O in healthy subjects after single and multiple dosing, as well as the food effect on pharmacokinetics and safety of HEC113995PA·H2O.MethodsThe entire study was comprised of three parts: Part I (single ascending-dose study), Part II (food effect study), and Part III (multiple ascending-dose study). A total of 121 healthy subjects were enrolled in the study. HEC113995PA·H2O tablet or placebo was administered per protocol requirements. Blood samples were collected at the designated time points for pharmacokinetic analysis. Safety was assessed by clinical examinations and adverse events.ResultsIn Part I, AUC and Cmax were found to by and large linear within the 2.5–80 mg dose range. t1/2 of HEC113995PA·H2O was 27.17∼38.58 h. In Part II, we revealed that HEC113995PA·H2O administration post meal could increase Cmax and AUC0-t. In Part III, multiple administration led to accumulated body exposure and the PK of healthy subjects reached a steady state after 7 days of continuous administration in each dose group.ConclusionHEC113995PA·H2O was safe and generally well-tolerated in healthy subjects. Based on the pharmacokinetic and safety data mentioned above, we expect that postprandial administration will favorably increase drug concentrations in the body and reduce gastrointestinal adverse events.https://www.frontiersin.org/articles/10.3389/fphar.2025.1500974/fullHEC113995PAH2OSPARIsafetypharmacokineticsfood effect |
| spellingShingle | Xue Wu Xue Wu Xue Wu Qingqing Wu Qingqing Wu Qingqing Wu Qichen Ding Qichen Ding Qichen Ding Yulei Zhuang Lin Luo Yingjun Zhang Li Deng Chuanfei Jin Xue Li Zhangma Huang Haiping Qin Liang Xin Liang Xin Liang Xin Qian Chen Qian Chen Qian Chen Jingying Jia Jingying Jia Jingying Jia Yanmei Liu Yanmei Liu Yanmei Liu A phase I study to evaluate the safety, tolerability, and pharmacokinetics of HEC113995PA·H2O, a novel dual-acting serotonergic antidepressant, in healthy subjects Frontiers in Pharmacology HEC113995PA H2O SPARI safety pharmacokinetics food effect |
| title | A phase I study to evaluate the safety, tolerability, and pharmacokinetics of HEC113995PA·H2O, a novel dual-acting serotonergic antidepressant, in healthy subjects |
| title_full | A phase I study to evaluate the safety, tolerability, and pharmacokinetics of HEC113995PA·H2O, a novel dual-acting serotonergic antidepressant, in healthy subjects |
| title_fullStr | A phase I study to evaluate the safety, tolerability, and pharmacokinetics of HEC113995PA·H2O, a novel dual-acting serotonergic antidepressant, in healthy subjects |
| title_full_unstemmed | A phase I study to evaluate the safety, tolerability, and pharmacokinetics of HEC113995PA·H2O, a novel dual-acting serotonergic antidepressant, in healthy subjects |
| title_short | A phase I study to evaluate the safety, tolerability, and pharmacokinetics of HEC113995PA·H2O, a novel dual-acting serotonergic antidepressant, in healthy subjects |
| title_sort | phase i study to evaluate the safety tolerability and pharmacokinetics of hec113995pa·h2o a novel dual acting serotonergic antidepressant in healthy subjects |
| topic | HEC113995PA H2O SPARI safety pharmacokinetics food effect |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1500974/full |
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