The partial positive allosteric GABAA receptor modulator EVT 201 is efficacious and safe in the treatment of adult primary insomnia patients

Walsh, James K.; Thacker, Steve; Knowles, Lisa J.; Tasker, Tim; Hunneyball, Ian

doi:10.1016/j.sleep.2008.10.005

Cited by 16 publications

(6 citation statements)

References 6 publications

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“…Other compounds in development for insomnia disorder target gamma‐aminobutyric acid receptors (eg, EVT‐201 and SAGE‐217), 74,75 which may not be appropriate for IAAC as previously discussed. Piromelatine, a melatonin MT1/2/3 and serotonin 5‐HT‐1A/1D receptors agonist, is in development for sleep disorders and Alzheimer's disease 76 .…”

Section: Resultsmentioning

confidence: 99%

Current and potential pharmacological treatment options for insomnia in patients with alcohol use disorder in recovery

Roehrs

Auciello

Tseng

et al. 2020

Neuropsychopharm Rep

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Alcohol use disorder (AUD) is characterized by dysfunction in motivational, mood‐stress regulation, and sleep systems that interact in complex ways to heighten the risk of relapse during abstinence. Emerging data suggest that excessive and chronic alcohol use disrupts sleep homeostasis and, in abstinence, subjects with AUD are known to experience insomnia that may persist for weeks to years, which we propose to refer to as insomnia associated with alcohol cessation (IAAC). The purpose of this review is to provide an update of pharmacological approaches to therapy including compounds in development, to raise awareness of the prevalence of and unmet need in IAAC and highlight differences in treatment consideration for IAAC as compared to insomnia disorder. We performed a search of select electronic databases to identify studies of pharmacological agents used to treat sleep disturbances in abstinent or treatment‐seeking patients with alcohol use disorder. The search, conducted in June 2019 and updated in December 2019, yielded 1,188 abstracts after duplicates were removed, of which 36 full‐text articles were assessed for eligibility. Eighteen studies were included, 15 randomized controlled trials and three open‐label studies. Several classes of medications including antidepressants, anticonvulsants, and antipsychotics have been evaluated for their effectiveness in treating sleep disturbances in abstinent or treatment‐seeking patients with AUD. None of these medications are approved by the FDA for the treatment of IAAC, and the currently available evidence for these agents is limited. Randomized, controlled clinical trials are warranted to evaluate the efficacy and safety of medications in the treatment of IAAC.

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Section: Resultsmentioning

confidence: 99%

Current and potential pharmacological treatment options for insomnia in patients with alcohol use disorder in recovery

Roehrs

Auciello

Tseng

et al. 2020

Neuropsychopharm Rep

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“…Dimdazenil, as a partial agonist, might lower the possibility of some adverse behavioral effects relative to full agonists (particularly at high doses) theoretically [ 36 , 37 ]. In this study, the incidence of TEAEs was 47.41% (174/367) and 39.89% (71/178) in the Dimdazenil group and placebo group, respectively ( P = 0.1); the incidence of drug-related TEAEs was 29.97% (110/367) and 21.91% (39/178), respectively ( P = 0.052).…”

Section: Discussionmentioning

confidence: 99%

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

Huang,

Zhan,

Chen

et al. 2023

Sleep

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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 included the average subjective sleep latency (sSL), subjective total sleep time (sTST), subjective sleep efficiency (sSE), subjective wake after sleep onset (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 min, respectively; both p <0.001), increased SE (13.26%, 5.55%, respectively; both <0.001), reduced WASO (49.67, 20.16 min, respectively; both p <0.001), reduced LPS (21.65min, p <0.001; 6.46 min, p =0.023). Compared to placebo, Dimdazenil also improved key self-reported measures of sTST (18.33 min, p <0.001), sWASO (14.60 min, p <0.001), sSL (4.23 min, p <0.001), sSE (2.97%, p <0.001), sNAW (0.29, p <0.001). Participants treated with Dimdazenil reported a significant improvement in insomnia severity index (ISI). Dimdazenil was well tolerated. The majority of TEAEs were mild or moderate. There were no clinically-relevant treatment-related serious adverse events 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.

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“…EVT-201 decreases sleep latency and increases total sleep time in human [Walsh et al, 2010]. The drug's elimination profile suggested that it is possible to identify a dose range with a duration of action sufficient to sustain sleep longer than with recommended doses of short-acting BZs, but less likely to produce residual effects than intermediate or long-acting BZs [Walsh et al, 2009[Walsh et al, , 2010. Another shortcoming of BZs is that the sleep that they induce is often not physiological [Borbely et al, 1983[Borbely et al, , 1985[Borbely et al, , 1991Scharf et al, 1994] highlighting the need for new approaches to treat insomnia.…”

Section: Gaba and Glutamate Systems In Inosmniamentioning

confidence: 99%

The Molecular Basis of Insomnia: Implication for Therapeutic Approaches

Wang

Liu

2016

Drug Development Research

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Preclinical Research Insomnia is one of the most common sleep disorders that is characterized by difficulty in sleep initiation, sleep maintenance, and/or poor sleep quality. Treatment for insomnia includes both pharmacological and non-pharmacological interventions. Recently, the development of pharmacological treatment for insomnia has been prompted by the understanding of the molecular neurobiology of sleep-wake regulation. For pharmacological treatment, benzodiazepines that target GABAergic system are the most widely used hypnotics. Besides GABA, the hypocretin/orexin system, and the hypothalamic-pituitary-adrenal (HPA) axis are involved in sleep-wake regulation and may also play important role in the pathogenesis of insomnia. Genetic studies have revealed the critical role of several important genes related to the above-mentioned systems in the regulation and function of sleep, suggesting the genetic/epigenetic factors could also contribute to the development and regulation of insomnia. Non-pharmacological interventions include cognitive behavioral therapy for insomnia (CBT-I) that is an effective insomnia treatment with less risk and side effects of drug therapy. Here the current treatments for insomnia based on the molecular mechanisms underlying sleep-wake regulation, were reviewed and some newer targets that may be beneficial in the development of new treatments for insomnia were discussed. Drug Dev Res 77 : 427-436, 2016. © 2016 Wiley Periodicals, Inc.

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The partial positive allosteric GABAA receptor modulator EVT 201 is efficacious and safe in the treatment of adult primary insomnia patients

Cited by 16 publications

References 6 publications

Current and potential pharmacological treatment options for insomnia in patients with alcohol use disorder in recovery

Current and potential pharmacological treatment options for insomnia in patients with alcohol use disorder in recovery

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

The Molecular Basis of Insomnia: Implication for Therapeutic Approaches

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