Lei Huang, Runbin Sun, Hengwen Song, Zhiyou Chen, Yuxin Hong, Haoyi Yang, Yuwen Zhang, Lijun Wei, Fei Fei, Juan Li
{"title":"QHRD106作为一种安全有效的长效降凝血酶药物，可能有助于缺血性中风，这是首次进行人体研究。","authors":"Lei Huang, Runbin Sun, Hengwen Song, Zhiyou Chen, Yuxin Hong, Haoyi Yang, Yuwen Zhang, Lijun Wei, Fei Fei, Juan Li","doi":"10.1080/13543784.2024.2430200","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>This study assessed the pharmacokinetics (PK), pharmacodynamics (PD) and safety of QHRD106, and made a comparison with urinary kallindinogenase (UKN) in healthy volunteers.</p><p><strong>Methods: </strong>This study comprised a randomized, double-blind, placebo-controlled, single-dose escalation phase and an open-label, multiple-dose escalation phase. Ninety-four subjects received intramuscular injections of QHRD106/placebo only once and 30 subjects received QHRD106 four times. Six subjects received 0.15 PNA units UKN intravenously for 7 d. PK and PD analysis were conducted by using a electrochemiluminescent assay and a liquid chromatography/mass spectrometry methodology, respectively. Cerebral circulation was assessed by the magnetic resonance imaging system.</p><p><strong>Results: </strong>QHRD106 exhibited a slow absorption profile in the human body. Compared to UKN, QHRD106-induced changes in bradykinin concentration later, but with a noticeably prolonged duration. Compared to baseline, cerebral blood flow exhibited a significant improvement on d 7 after a single dose of 18,900 IU and an improvement from d 2 to d 14 after multiple doses of 8400 IU of QHRD106. QHRD106 appeared generally good safety and no severe adverse events occurred in all the groups.</p><p><strong>Conclusions: </strong>This study provided initial evidence of potential treatment for ischemic strokes that the QHRD106 injection functioned as a safe and effective long-acting kallikrein drug.</p><p><strong>Registration: </strong>This study was registered on ClinicalTrials.gov with the identifier NCT06380699 and NCT06388772.</p>","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1-9"},"PeriodicalIF":4.9000,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The first-in-human study of QHRD106 functioning as a safe and effective long-acting kallikrein drug potentially aiding ischemic stroke.\",\"authors\":\"Lei Huang, Runbin Sun, Hengwen Song, Zhiyou Chen, Yuxin Hong, Haoyi Yang, Yuwen Zhang, Lijun Wei, Fei Fei, Juan Li\",\"doi\":\"10.1080/13543784.2024.2430200\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>This study assessed the pharmacokinetics (PK), pharmacodynamics (PD) and safety of QHRD106, and made a comparison with urinary kallindinogenase (UKN) in healthy volunteers.</p><p><strong>Methods: </strong>This study comprised a randomized, double-blind, placebo-controlled, single-dose escalation phase and an open-label, multiple-dose escalation phase. Ninety-four subjects received intramuscular injections of QHRD106/placebo only once and 30 subjects received QHRD106 four times. Six subjects received 0.15 PNA units UKN intravenously for 7 d. PK and PD analysis were conducted by using a electrochemiluminescent assay and a liquid chromatography/mass spectrometry methodology, respectively. Cerebral circulation was assessed by the magnetic resonance imaging system.</p><p><strong>Results: </strong>QHRD106 exhibited a slow absorption profile in the human body. Compared to UKN, QHRD106-induced changes in bradykinin concentration later, but with a noticeably prolonged duration. Compared to baseline, cerebral blood flow exhibited a significant improvement on d 7 after a single dose of 18,900 IU and an improvement from d 2 to d 14 after multiple doses of 8400 IU of QHRD106. QHRD106 appeared generally good safety and no severe adverse events occurred in all the groups.</p><p><strong>Conclusions: </strong>This study provided initial evidence of potential treatment for ischemic strokes that the QHRD106 injection functioned as a safe and effective long-acting kallikrein drug.</p><p><strong>Registration: </strong>This study was registered on ClinicalTrials.gov with the identifier NCT06380699 and NCT06388772.</p>\",\"PeriodicalId\":12313,\"journal\":{\"name\":\"Expert opinion on investigational drugs\",\"volume\":\" \",\"pages\":\"1-9\"},\"PeriodicalIF\":4.9000,\"publicationDate\":\"2024-11-19\",\"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/10.1080/13543784.2024.2430200\",\"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/10.1080/13543784.2024.2430200","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
The first-in-human study of QHRD106 functioning as a safe and effective long-acting kallikrein drug potentially aiding ischemic stroke.
Background: This study assessed the pharmacokinetics (PK), pharmacodynamics (PD) and safety of QHRD106, and made a comparison with urinary kallindinogenase (UKN) in healthy volunteers.
Methods: This study comprised a randomized, double-blind, placebo-controlled, single-dose escalation phase and an open-label, multiple-dose escalation phase. Ninety-four subjects received intramuscular injections of QHRD106/placebo only once and 30 subjects received QHRD106 four times. Six subjects received 0.15 PNA units UKN intravenously for 7 d. PK and PD analysis were conducted by using a electrochemiluminescent assay and a liquid chromatography/mass spectrometry methodology, respectively. Cerebral circulation was assessed by the magnetic resonance imaging system.
Results: QHRD106 exhibited a slow absorption profile in the human body. Compared to UKN, QHRD106-induced changes in bradykinin concentration later, but with a noticeably prolonged duration. Compared to baseline, cerebral blood flow exhibited a significant improvement on d 7 after a single dose of 18,900 IU and an improvement from d 2 to d 14 after multiple doses of 8400 IU of QHRD106. QHRD106 appeared generally good safety and no severe adverse events occurred in all the groups.
Conclusions: This study provided initial evidence of potential treatment for ischemic strokes that the QHRD106 injection functioned as a safe and effective long-acting kallikrein drug.
Registration: This study was registered on ClinicalTrials.gov with the identifier NCT06380699 and NCT06388772.
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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