The first-in-human study of QHRD106 functioning as a safe and effective long-acting kallikrein drug potentially aiding ischemic stroke.

IF 4.9 2区医学 Q1 PHARMACOLOGY & PHARMACY Expert opinion on investigational drugs Pub Date : 2024-11-19 DOI:10.1080/13543784.2024.2430200

Lei Huang, Runbin Sun, Hengwen Song, Zhiyou Chen, Yuxin Hong, Haoyi Yang, Yuwen Zhang, Lijun Wei, Fei Fei, Juan Li

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Abstract

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.

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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。

背景：本研究评估了QHRD106在健康志愿者中的药代动力学（PK）、药效学（PD）和安全性，并与尿中凯林胰岛素原酶（UKN）进行了比较：该研究包括随机、双盲、安慰剂对照、单剂量递增阶段和开放标签、多剂量递增阶段。94名受试者只接受了一次QHRD106/安慰剂肌肉注射，30名受试者接受了四次QHRD106肌肉注射。PK 和 PD 分析分别采用电化学发光法和液相色谱/质谱法进行。磁共振成像系统对脑循环进行了评估：结果：QHRD106 在人体内的吸收速度较慢。与 UKN 相比，QHRD106 引起缓激肽浓度变化的时间更晚，但持续时间明显更长。与基线相比，单次服用18900 IU后，脑血流量在第7天有明显改善；多次服用8400 IU QHRD106后，脑血流量在第2天至第14天均有改善。QHRD106的安全性总体良好，各组均未出现严重不良反应：这项研究为缺血性脑卒中的潜在治疗提供了初步证据，证明QHRD106注射液是一种安全有效的长效降钙素药物：本研究已在ClinicalTrials.gov上注册，标识符为NCT06380699和NCT06388772。

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来源期刊

Expert opinion on investigational drugs 医学-药学

CiteScore

10.00

自引率

0.00%

发文量

审稿时长

6-12 weeks

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.