Safety, tolerability, and pharmacokinetics of JX11502MA in Chinese healthy subjects: a first-in-human, randomized, double-blind, placebo-controlled study following single-dose administration.

IF 4.9 2区医学 Q1 PHARMACOLOGY & PHARMACY

Expert opinion on investigational drugs Pub Date : 2024-01-01 Epub Date: 2024-02-12 DOI:10.1080/13543784.2023.2291470

Yimin Yu, Jingjing He, Zhiwei Huang, Yan Li, Ying Wu, Yifeng Shen, Yanling Zhou, Cungang Bao, Zhiping Jin, Huafang Li

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引用次数: 0

Abstract

Background: JX11502MA is a potent partial agonist of dopamine D2 and D3 receptors, with a preferential binding profile for D3 receptors in vitro, potentially for treating schizophrenia.

Methods: A first-in-human, randomized, double-blind, placebo-controlled, single ascending dose clinical trial was designed. The subjects were randomly assigned to receive JX11502MA and placebo capsules with seven ascending dose groups: 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 6 mg, and 8 mg. The PK profiles of JX11502MA and its metabolites were evaluated, along with a safety and tolerability assessment.

Results: Considering the safety of participants, the dose escalation was halted at 3 mg. Following single-dose administration, JX11502MA exhibited rapid absorption with a median T_max ranging from 1 to 1.75 h. The terminal half-life of JX11502MA ranged from 73.62 to 276.85 h. The most common treatment-emergent adverse events (TEAEs) for subjects receiving JX11502MA were somnolence (56.3%), dizziness (18.8%), nausea (21.9%), vomiting (18.8%), and hiccups (18.8%).

Conclusions: JX11502MA was generally well tolerated at a single dose of 0.25 to 3 mg. The PK profiles and safety characteristics in this study indicated that JX11502MA has the potential to be a favorable treatment option for patients with schizophrenia.

Trial registration: https://clinicaltrials.gov (identifier: NCT05233657).

查看原文本刊更多论文

JX11502MA 在中国健康受试者中的安全性、耐受性和药代动力学：一项首次在人体中进行的单剂量给药后随机、双盲、安慰剂对照研究。

背景：JX11502MA是一种强效的多巴胺D2和D3受体部分激动剂，在体外与D3受体有优先结合特性，可能用于治疗精神分裂症：设计了一项首次人体随机、双盲、安慰剂对照、单剂量递增临床试验。受试者被随机分配到接受JX11502MA和安慰剂胶囊的七个递增剂量组：0.25毫克、0.5毫克、1毫克、2毫克、3毫克、6毫克和8毫克。对JX11502MA及其代谢物的PK谱进行了评估，同时还进行了安全性和耐受性评估：结果：考虑到参与者的安全性，剂量升级在 3 毫克时停止。单剂量给药后，JX11502MA吸收迅速，中位Tmax为1至1.75小时。接受JX11502MA治疗的受试者最常见的治疗突发不良事件（TEAEs）为嗜睡（56.3%）、头晕（18.8%）、恶心（21.9%）、呕吐（18.8%）和打嗝（18.8%）：JX11502MA单次剂量为0.25至3毫克时，耐受性总体良好。本研究的PK曲线和安全性特征表明，JX11502MA有可能成为精神分裂症患者的一种有利治疗选择。试验注册：https://clinicaltrials.gov（标识符：NCT05233657）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.