A phase 1 study of dimdazenil to evaluate the pharmacokinetics, food effect and safety in Chinese healthy subjects

作者：Fei Wang, Jingjing He, Yanling Zhou, Lijun Ye, Bei Li, Zhiyuan Ma, Chunyan Chen, Ruoxi Zhang, Zhaocun Lin, Jinshan Tang, Zhiping Jin, Yu Jiang, Nengming Lin · 发表于：Frontiers in Pharmacology · 年份：2023 · DOI：10.3389/fphar.2023.1226014 · 被引用次数：9 · 研究领域：Neuroscience and Neuropharmacology Research、Sleep and Wakefulness Research、GABA and Rice Research

Background and objective: As a partial positive allosteric modulator of the gamma-aminobutyric acid A (GABAA) receptor, dimdazenil was used for the treatment of insomnia with the potential to alleviate associated side effects compared to full agonists. The objective of this trial is to assess the safety, tolerability, food effect and pharmacokinetics following single and multiple doses of dimdazenil in Chinese healthy subjects. Methods: In this phase 1 trial, 36 healthy subjects aged ≥18 years were assigned to receive a single dose of 1.5, 2.5, or 5 mg dimdazenil, with each dose cohort consisting of 12 subjects, and 14 subjects were assigned to receive a multiple 2.5 mg daily dose of dimdazenil for 5 days. Safety, tolerability, and pharmacokinetic characteristics were evaluated. Results: Of the 50 subjects enrolled and 49 completed the trial, the incidences of treatment-emergent adverse events (AEs) in the single-dose groups of 1.5, 2.5, and 5 mg were 16.7%, 58.3% and 66.7% respectively, while 61.5% in the multiple-dose group. There were no serious AEs, deaths, AEs leading to discontinuation or AEs of requiring clinical intervention in any treatment groups. The most treatment-emergent AEs were dizziness ( n = 4, 8.2%), hyperuricemia ( n = 2, 6.1%), upper respiratory tract infection ( n = 2, 6.1%), diastolic blood pressure decreased ( n = 2, 6.1%), blood TG increased ( n = 2, 6.1%) and RBC urine positive ( n = 2, 6.1%). All AEs were mild-to-moderate and transient, and no sever...