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Clinical Trial
. 2024 Feb 8;47(2):zsad272.
doi: 10.1093/sleep/zsad272.

Efficacy and safety of Dimdazenil in adults with insomnia disorder: results from a multicenter, randomized, double-blind, placebo-controlled phase III trials

Zhaoyang Huang  1   2 , Shuqin Zhan  1   2 , Chunyan Chen  3 , Ruoxi Zhang  3 , Yanling Zhou  3 , Jingjing He  3 , Zhaocun Lin  3 , Cungang Bao  3 , Shuangpeng Zhu  4 , Jianjun Zhao  3 , Shengan Zhang  3 , Yu Jiang  3 , Yuping Wang  1   2
Affiliations
Clinical Trial

Efficacy and safety of Dimdazenil in adults with insomnia disorder: results from a multicenter, randomized, double-blind, placebo-controlled phase III trials

Zhaoyang Huang et al. Sleep. .

Abstract

Study objectives: To evaluate the efficacy and safety of Dimdazenil, a novel partial positive allosteric modulator for GABAA receptor in adults with insomnia disorder.

Methods: This was a 2-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group phase III study of Dimdazenil. The primary efficacy outcome was total sleep time (TST) analyzed by polysomnography (PSG) on day 13/14. Latency to persistent sleep (LPS), sleep efficiency (SE), and wake after sleep onset (WASO) were analyzed in the same way by polysomnography (PSG). The other secondary outcomes including the average subjective sleep latency (sSL), subjective TST (sTST), subjective SE (sSE), subjective WASO (sWASO), and subjective number of awakenings (sNAW) were analyzed from sleep diary data, and the insomnia severity index (ISI) was also assessed. Treatment-emergent adverse events (TEAEs) were monitored throughout the study.

Results: A total of 546 participants with insomnia (age ≥18 years) were randomized (2:1), received treatment with an oral dose of Dimdazenil (2.5 mg) or placebo, and analyzed. Compared to baseline and placebo, Dimdazenil demonstrated significant improvements in PSG measures, increased TST (71.09, 31.68 minutes, respectively; both p < 0.001), increased SE (13.26%, 5.55%, respectively; both < 0.001), reduced WASO (49.67, 20.16 minutes, respectively; both p < 0.001), and reduced LPS (21.65 minutes, p < 0.001; 6.46 minutes, p = 0.023). Compared to placebo, Dimdazenil also improved key self-reported measures of sTST (18.33 minutes, p < 0.001), sWASO (14.60 minutes, p < 0.001), sSL (4.23 minutes, p < 0.001), sSE (2.97%, p < 0.001), and sNAW (0.29, p < 0.001). Participants treated with Dimdazenil reported a significant improvement in ISI. Dimdazenil was well tolerated. The majority of TEAEs were mild or moderate. There were no clinically relevant treatment-related serious AEs and no deaths.

Conclusions: Dimdazenil of 2.5 mg provided significant benefit on sleep maintenance and sleep onset in individuals with insomnia disorder versus placebo, with a favorable safety profile and was well tolerated.

Clinical trial information: A multicenter, randomized, double-blind phase III clinical study evaluating the efficacy and safety of EVT201 capsules compared to placebo in patients with insomnia disorders (http://www.chinadrugtrials.org), with the number of CTR20201068.

Keywords: Dimdazenil; GABAA receptors; insomnia disorder; partial positive allosteric modulator; polysomnography.

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Figures

Graphical Abstract
Graphical Abstract
Figure 1.
Figure 1.
The study flow diagram.
Figure 2.
Figure 2.
Subgroup analysis of PSG TST. TST on each subgroup for Dimdazenil was longer than placebo (>20 minutes). The lower limit CI of the 95% difference in TST was below zero in sleep latency ≤ 30 minutes subgroup (highlighted). *p < 0.05; DSM, Diagnostic and Statistical Manual of Mental Disorders; PSG, polysomnography; CI, confidence interval.
Figure 3.
Figure 3.
Analysis of sleep architecture at day 13/14. *p < 0.05; REM, rapid eye movement.
See this image and copyright information in PMC

Comment in

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