{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T02:13:58Z","timestamp":1783476838421,"version":"3.55.0"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2023,10,21]],"date-time":"2023-10-21T00:00:00Z","timestamp":1697846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,2,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Study Objectives<\/jats:title>\n                  <jats:p>To evaluate the efficacy and safety of Dimdazenil, a positive allosteric modulator with selectivity for \u03b11, \u03b15 subunit-containing GABAA receptors, on sleep variables in patients with insomnia disorder.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In this randomized, double-blind, placebo-controlled trial, adults (18\u201365 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>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), (\u22128.24, 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Trial Information<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/sleep\/zsad271","type":"journal-article","created":{"date-parts":[[2023,10,21]],"date-time":"2023-10-21T18:33:38Z","timestamp":1697913218000},"source":"Crossref","is-referenced-by-count":7,"title":["Efficacy and safety of Dimdazenil in the adult insomnia patients: a phase II randomized, multicenter, double-blind, placebo-controlled, and parallel-group study"],"prefix":"10.1093","volume":"47","author":[{"given":"Yanpeng","family":"Li","sequence":"first","affiliation":[{"name":"Neurology Department, Shanghai Changzheng Hospital , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoxi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanghai Research Institute, Zhejiang Jingxin Pharmaceutical Co., Ltd , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanling","family":"Zhou","sequence":"additional","affiliation":[{"name":"Shanghai Research Institute, Zhejiang Jingxin Pharmaceutical Co., Ltd , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cungang","family":"Bao","sequence":"additional","affiliation":[{"name":"Shanghai Research Institute, Zhejiang Jingxin Pharmaceutical Co., Ltd , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaocun","family":"Lin","sequence":"additional","affiliation":[{"name":"Shanghai Research Institute, Zhejiang Jingxin Pharmaceutical Co., Ltd , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyan","family":"Chen","sequence":"additional","affiliation":[{"name":"Shanghai Research Institute, Zhejiang Jingxin Pharmaceutical Co., Ltd , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"He","sequence":"additional","affiliation":[{"name":"Shanghai Research Institute, Zhejiang Jingxin Pharmaceutical Co., Ltd , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiping","family":"Jin","sequence":"additional","affiliation":[{"name":"The president's office, Zhejiang Jingxin Pharmaceutical Co., Ltd , Zhejiang , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihua","family":"Song","sequence":"additional","affiliation":[{"name":"Shanghai Research Institute, Zhejiang Jingxin Pharmaceutical Co., Ltd , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanghai Research Institute, Zhejiang Jingxin Pharmaceutical Co., Ltd , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigen","family":"Guo","sequence":"additional","affiliation":[{"name":"Shanghai Research Institute, Zhejiang Jingxin Pharmaceutical Co., Ltd , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Jiang","sequence":"additional","affiliation":[{"name":"Shanghai Research Institute, Zhejiang Jingxin Pharmaceutical Co., Ltd , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongxin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Neurology Department, Shanghai Changzheng Hospital , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,10,21]]},"reference":[{"key":"2024020814053228100_CIT0001","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1053\/smrv.2002.0186","article-title":"Epidemiology of insomnia: what we know and what we still need to learn","volume":"6","author":"Ohayon","year":"2002","journal-title":"Sleep Med Rev."},{"key":"2024020814053228100_CIT0002","doi-asserted-by":"crossref","first-page":"3101","DOI":"10.3889\/oamjms.2019.771","article-title":"The effects of magnesium - melatonin - Vit B complex supplementation in treatment of insomnia","volume":"7","author":"Djokic","year":"2019","journal-title":"Open Access Maced J Med Sci."},{"key":"2024020814053228100_CIT0003","doi-asserted-by":"crossref","first-page":"4943","DOI":"10.2174\/1381612821666150914121624","article-title":"GABA receptors: pharmacological potential and pitfalls","volume":"21","author":"Jembrek","year":"2015","journal-title":"Curr Pharm Des."},{"key":"2024020814053228100_CIT0004","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.coph.2005.10.003","article-title":"GABA-based therapeutic approaches: GABAA receptor subtype functions","volume":"6","author":"Rudolph","year":"2006","journal-title":"Curr Opin Pharmacol."},{"key":"2024020814053228100_CIT0005","doi-asserted-by":"crossref","first-page":"616298","DOI":"10.3389\/fnins.2020.616298","article-title":"Looking for novelty in an \u201cold\u201d receptor: recent advances toward our understanding of GABA(A)Rs and their implications in receptor pharmacology","volume":"14","author":"Castellano","year":"2020","journal-title":"Front Neurosci."},{"key":"2024020814053228100_CIT0006","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/S0306-4522(02)00034-9","article-title":"GABA mechanisms and sleep","volume":"111","author":"Gottesmann","year":"2002","journal-title":"Neuroscience."},{"key":"2024020814053228100_CIT0007","doi-asserted-by":"crossref","first-page":"2218","DOI":"10.1016\/j.biopha.2018.10.003","article-title":"Sedative and hypnotic effects of Vaccinium bracteatum Thunb through the regulation of serotonegic and GABA(A)-ergic systems: Involvement of 5-HT(1A) receptor agonistic activity","volume":"109","author":"Oh","year":"2019","journal-title":"Biomed Pharmacother."},{"key":"2024020814053228100_CIT0008","doi-asserted-by":"crossref","first-page":"1134434","DOI":"10.3389\/fpsyt.2023.1134434","article-title":"Impairment of GABA inhibition in insomnia disorders: evidence from the peripheral blood system","volume":"14","author":"Xiang","year":"2023","journal-title":"Front Psychiatry."},{"key":"2024020814053228100_CIT0009","volume-title":"Diagnostic and statistical manual of mental disorders (5th edition)","author":"APA","year":"2013","edition":"5"},{"key":"2024020814053228100_CIT0010","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1002\/ana.25680","article-title":"Daridorexant, a new dual orexin receptor antagonist to treat insomnia disorder","volume":"87","author":"Dauvilliers","year":"2020","journal-title":"Ann Neurol."},{"key":"2024020814053228100_CIT0011","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/S1389-9457(00)00065-4","article-title":"Validation of the Insomnia Severity Index as an outcome measure for insomnia research","volume":"2","author":"Bastien","year":"2001","journal-title":"Sleep Med."},{"key":"2024020814053228100_CIT0012","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/0165-0327(90)90009-W","article-title":"The benzodiazepine withdrawal symptom questionnaire","volume":"19","author":"Tyrer","year":"1990","journal-title":"J Affect Disord."},{"key":"2024020814053228100_CIT0013","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1177\/1740774515602688","article-title":"Fallacies of last observation carried forward analyses","volume":"13","author":"Lachin","year":"2016","journal-title":"Clin Trials."},{"key":"2024020814053228100_CIT0014","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3389\/fncel.2019.00077","article-title":"Alterations in GABA(A)-receptor trafficking and synaptic dysfunction in brain disorders","volume":"13","author":"Mele","year":"2019","journal-title":"Front Cell Neurosci."},{"key":"2024020814053228100_CIT0015","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S1474-4422(21)00436-1","article-title":"Safety and efficacy of daridorexant in patients with insomnia disorder: results from two multicentre, randomised, double-blind, placebo-controlled, phase 3 trials","volume":"21","author":"Mignot","year":"2022","journal-title":"Lancet Neurol."},{"key":"2024020814053228100_CIT0016","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1111\/jsr.12046","article-title":"The subjective-objective mismatch in sleep perception among those with insomnia and sleep apnea","volume":"22","author":"Bianchi","year":"2013","journal-title":"J Sleep Res."},{"key":"2024020814053228100_CIT0017","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/1471-2202-15-109","article-title":"Differential sleep-promoting effects of dual orexin receptor antagonists and GABAA receptor modulators","volume":"15","author":"Gotter","year":"2014","journal-title":"BMC Neurosci."},{"issue":"10","key":"2024020814053228100_CIT0018","doi-asserted-by":"crossref","DOI":"10.1093\/sleep\/zsaa080","article-title":"Acute cognitive effects of the hypocretin receptor antagonist almorexant relative to zolpidem and placebo: a randomized clinical trial","volume":"43","author":"Neylan","year":"2020","journal-title":"Sleep."},{"key":"2024020814053228100_CIT0019","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.sleep.2021.01.048","article-title":"Long-term effectiveness and safety of lemborexant in adults with insomnia disorder: results from a phase 3 randomized clinical trial","volume":"80","author":"Yardley","year":"2021","journal-title":"Sleep Med."},{"key":"2024020814053228100_CIT0020","doi-asserted-by":"crossref","first-page":"172","DOI":"10.2174\/1871527320666210618103344","article-title":"Benzodiazepines and sleep architecture: a systematic review","volume":"22","author":"de Mendon\u00e7a","year":"2023","journal-title":"CNS Neurol Disord Drug Targets."},{"key":"2024020814053228100_CIT0021","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/s41586-018-0255-3","article-title":"Structure of a human synaptic GABA(A) receptor","volume":"559","author":"Zhu","year":"2018","journal-title":"Nature."},{"key":"2024020814053228100_CIT0022","doi-asserted-by":"crossref","first-page":"252","DOI":"10.3390\/neurolint13020026","article-title":"Cenobamate, a sodium Channel inhibitor and positive allosteric modulator of GABA(A) ion channels, for partial onset seizures in adults: a comprehensive review and clinical implications","volume":"13","author":"Latimer","year":"2021","journal-title":"Neurol Int."},{"key":"2024020814053228100_CIT0023","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1007\/s40263-021-00819-8","article-title":"Pharmacology of cenobamate: mechanism of action, pharmacokinetics, drug-drug interactions and tolerability","volume":"35","author":"Roberti","year":"2021","journal-title":"CNS Drugs."}],"container-title":["SLEEP"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/sleep\/advance-article-pdf\/doi\/10.1093\/sleep\/zsad271\/52964764\/zsad271.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/sleep\/article-pdf\/47\/2\/zsad271\/56616498\/zsad271.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/sleep\/article-pdf\/47\/2\/zsad271\/56616498\/zsad271.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T14:40:49Z","timestamp":1707403249000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/sleep\/article\/doi\/10.1093\/sleep\/zsad271\/7326687"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,21]]},"references-count":23,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,10,21]]},"published-print":{"date-parts":[[2024,2,8]]}},"URL":"https:\/\/doi.org\/10.1093\/sleep\/zsad271","relation":{},"ISSN":["0161-8105","1550-9109"],"issn-type":[{"value":"0161-8105","type":"print"},{"value":"1550-9109","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,2,1]]},"published":{"date-parts":[[2023,10,21]]},"article-number":"zsad271"}}