Efficacy and safety of Dimdazenil in the adult insomnia patients : a phase II randomized, multicenter, double-blind, placebo-controlled, and parallel-group study
© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society..
STUDY OBJECTIVES: To evaluate the efficacy and safety of Dimdazenil, a positive allosteric modulator with selectivity for α1, α5 subunit-containing GABAA receptors, on sleep variables in patients with insomnia disorder.
METHODS: In this randomized, double-blind, placebo-controlled trial, adults (18-65 years) with insomnia disorder were randomized (1:1:1:1 to receive daily oral placebo, Dimdazenil (1.5, 2.5, or 5 mg) for 14 days. The primary efficacy outcome was the total sleep time (TST) on day 1/2 and day 13/14, measured by polysomnography. The secondary outcome measures included (1) latency to persistent sleep (LPS), sleep efficiency (SE), wake after sleep onset (WASO) and number of awakenings (NAW) on days 1/2 and day 13/14, and (2) the average subjective sleep latency (sSL), total sleep time (sTST), wake after sleep onset (sWASO) and number of awakenings (sNAW) recorded in sleep diary and sleep questionnaire, and the evaluation of insomnia severity index. Rebound insomnia, withdrawal, and treatment-emergent adverse events were also assessed.
RESULTS: Of 569 patients screened, 288 (76.4% female) were randomized and received one dose. For the primary outcomes, TST was significantly improved in the Dimdazenil 1.5, 2.5, and 5 mg group compared with the placebo group at day 1/2, and significantly improved in the Dimdazenil 2.5 and 5 mg groups compared with the placebo group at day 13/14. The Least Squares Means (standard errors) and 95% Confidence Intervals for the three active doses compared to placebo are 25.5 (8.31), (9.16, 41.89) for the 1.5 mg dose; 17.4 (8.19), (1.29, 33.55) for the 2.5 mg dose; 22.8 (8.15), (6.72, 38.80) for the 5 mg dose on day 1/2. Corresponding data on day 13/14 are 7.6 (8.07), (-8.24, 23.53) and 19.3 (8.06), (3.43, 35.17) and 18.2 (7.95), (2.49, 33.80). LPS was significantly reduced in the Dimdazenil 5 mg group compared with the placebo group on day 1/2. SE was significantly improved in the Dimdazenil 1.5 and 5 mg group compared with the placebo group at day 1/2. In the subjective sleep parameters, sSL on average was significantly lower in the Dimdazenil 1.5, 2.5, and 5 mg groups compared with the placebo group. sTST on average was significantly higher in the Dimdazenil 1.5, 2.5, and 5 mg groups compared with the placebo group. The most common TEAEs were dizziness, vertigo, and weakness with no clinically relevant treatment-related serious adverse events.
CONCLUSIONS: Dimdazenil of 1.5, 2.5, and 5 mg improved certain objective and subjective sleep outcomes in people with insomnia disorder, with a favorable safety profile. These findings suggested that Dimdazenil may represent a promising new treatment for insomnia disorder, a prevalent condition with limited effective and safe treatments available.
CLINICAL TRIAL INFORMATION: A multicenter, randomized, double-blind, multidose, placebo parallel controlled phase II clinical study of EVT201 in the treatment of insomnia disorders (http://www.chinadrugtrials.org), with the number of CTR20150664.
| Errataetall: | |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:47 |
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| Enthalten in: |
Sleep - 47(2024), 2 vom: 08. Feb. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Yanpeng [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 20.02.2024 Date Revised 20.02.2024 published: Print CommentIn: Sleep. 2023 Dec 04;:. - PMID 38044567 Citation Status MEDLINE |
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| doi: |
10.1093/sleep/zsad271 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Li, Yanpeng |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Efficacy and safety of Dimdazenil in the adult insomnia patients |b a phase II randomized, multicenter, double-blind, placebo-controlled, and parallel-group study |
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| 500 | |a Date Revised 20.02.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a CommentIn: Sleep. 2023 Dec 04;:. - PMID 38044567 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society. | ||
| 520 | |a STUDY OBJECTIVES: To evaluate the efficacy and safety of Dimdazenil, a positive allosteric modulator with selectivity for α1, α5 subunit-containing GABAA receptors, on sleep variables in patients with insomnia disorder | ||
| 520 | |a METHODS: In this randomized, double-blind, placebo-controlled trial, adults (18-65 years) with insomnia disorder were randomized (1:1:1:1 to receive daily oral placebo, Dimdazenil (1.5, 2.5, or 5 mg) for 14 days. The primary efficacy outcome was the total sleep time (TST) on day 1/2 and day 13/14, measured by polysomnography. The secondary outcome measures included (1) latency to persistent sleep (LPS), sleep efficiency (SE), wake after sleep onset (WASO) and number of awakenings (NAW) on days 1/2 and day 13/14, and (2) the average subjective sleep latency (sSL), total sleep time (sTST), wake after sleep onset (sWASO) and number of awakenings (sNAW) recorded in sleep diary and sleep questionnaire, and the evaluation of insomnia severity index. Rebound insomnia, withdrawal, and treatment-emergent adverse events were also assessed | ||
| 520 | |a RESULTS: Of 569 patients screened, 288 (76.4% female) were randomized and received one dose. For the primary outcomes, TST was significantly improved in the Dimdazenil 1.5, 2.5, and 5 mg group compared with the placebo group at day 1/2, and significantly improved in the Dimdazenil 2.5 and 5 mg groups compared with the placebo group at day 13/14. The Least Squares Means (standard errors) and 95% Confidence Intervals for the three active doses compared to placebo are 25.5 (8.31), (9.16, 41.89) for the 1.5 mg dose; 17.4 (8.19), (1.29, 33.55) for the 2.5 mg dose; 22.8 (8.15), (6.72, 38.80) for the 5 mg dose on day 1/2. Corresponding data on day 13/14 are 7.6 (8.07), (-8.24, 23.53) and 19.3 (8.06), (3.43, 35.17) and 18.2 (7.95), (2.49, 33.80). LPS was significantly reduced in the Dimdazenil 5 mg group compared with the placebo group on day 1/2. SE was significantly improved in the Dimdazenil 1.5 and 5 mg group compared with the placebo group at day 1/2. In the subjective sleep parameters, sSL on average was significantly lower in the Dimdazenil 1.5, 2.5, and 5 mg groups compared with the placebo group. sTST on average was significantly higher in the Dimdazenil 1.5, 2.5, and 5 mg groups compared with the placebo group. The most common TEAEs were dizziness, vertigo, and weakness with no clinically relevant treatment-related serious adverse events | ||
| 520 | |a CONCLUSIONS: Dimdazenil of 1.5, 2.5, and 5 mg improved certain objective and subjective sleep outcomes in people with insomnia disorder, with a favorable safety profile. These findings suggested that Dimdazenil may represent a promising new treatment for insomnia disorder, a prevalent condition with limited effective and safe treatments available | ||
| 520 | |a CLINICAL TRIAL INFORMATION: A multicenter, randomized, double-blind, multidose, placebo parallel controlled phase II clinical study of EVT201 in the treatment of insomnia disorders (http://www.chinadrugtrials.org), with the number of CTR20150664 | ||
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Dimdazenil | |
| 650 | 4 | |a GABAA receptors | |
| 650 | 4 | |a insomnia disorder | |
| 650 | 4 | |a polysomnography | |
| 650 | 4 | |a positive allosteric modulator | |
| 650 | 7 | |a Hypnotics and Sedatives |2 NLM | |
| 700 | 1 | |a Zhang, Ruoxi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Yanling |e verfasserin |4 aut | |
| 700 | 1 | |a Bao, Cungang |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Zhaocun |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Chunyan |e verfasserin |4 aut | |
| 700 | 1 | |a He, Jingjing |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Zhiping |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Lihua |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Sigen |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Zhongxin |e verfasserin |4 aut | |
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