Efficacy and Safety of Daridorexant in Older and Younger Adults with Insomnia Disorder: A Secondary Analysis of a Randomised Placebo-Controlled Trial.

Background And Objective: The dual orexin receptor antagonist daridorexant, studied in two phase III trials, dose-dependently improved objective and subjective sleep variables and daytime functioning in adults with insomnia. Because treatment of insomnia in older adults is challenging and has limited options, the purpose of the current analysis was to further analyse the phase III trial studying the higher doses of daridorexant, those that showed efficacy (daridorexant 50 mg, daridorexant 25 mg and placebo, nightly for 3 months), and compare the safety and efficacy of daridorexant in patients aged ≥ 65 ('older adults') to those aged < 65 years ('younger adults').

Methods: Analyses by age (≥ 65 years, n = 364; < 65 years, n = 566) were performed on data from the randomised, double-blind, placebo-controlled Trial 1 in adult patients with insomnia (NCT03545191).

Safety and efficacy of daridorexant in patients with insomnia disorder: results from two multicentre, randomised, double-blind, placebo-controlled, phase 3 trials.

Background: Daytime functioning is impaired in people with insomnia disorder. Currently available dual orexin receptor antagonists have shown efficacy in insomnia disorder, but do not address all aspects of this disease. We aimed to assess safety and efficacy of daridorexant, a novel orexin receptor antagonist, on night-time and daytime symptoms of insomnia.

Assessment of morning sleep propensity with lemborexant in adults with insomnia disorder in a randomized, placebo-controlled crossover study.

Objective: To evaluate effects of lemborexant (LEM), a dual orexin receptor antagonist, on next-morning sleep propensity assessed by a modified Multiple Sleep Latency Test (M-MSLT) in adults with insomnia disorder.

Methods: Study 107 (E2006-A001-107) was a phase 1, randomized, double-blind, four-period crossover study. Subjects ( = 69) received oral single-dose placebo, LEM 5 mg (LEM5), and LEM 10 mg (LEM10) at bedtime in periods 1-3 in a randomized crossover and open-label flurazepam 30 mg in period 4.

Comparison of the effect of lemborexant with placebo and zolpidem tartrate extended release on sleep architecture in older adults with insomnia disorder.

Study Objectives: Changes to sleep architecture that occur as a result of the normal aging process may also exacerbate insomnia in older individuals. Therefore, this study assessed the impact of lemborexant compared with placebo and zolpidem tartrate extended release on objective sleep architecture parameters, as measured by polysomnography, in older adults (ages ≥ 55 years) with insomnia disorder from a phase 3 study.

Methods: Study E2006-G000-304 (SUNRISE 1; NCT02783729) was a global, multicenter, randomized, double-blind, placebo-controlled, active comparator (zolpidem)-controlled, parallel-group study comparing 2 dose levels of lemborexant (5 mg and 10 mg).

Daridorexant, a New Dual Orexin Receptor Antagonist to Treat Insomnia Disorder.

Objective: To evaluate the dose-response relationship of daridorexant, a new dual orexin receptor antagonist, on sleep variables in subjects with insomnia disorder.

Methods: Adults (≤64 years) with insomnia disorder were randomized (1:1:1:1:1:1) to receive daily oral placebo, daridorexant (5, 10, 25, or 50mg), or 10mg zolpidem for 30 days. The primary efficacy outcome was the change in wake time after sleep onset from baseline to days 1 and 2.

Comparison of Lemborexant With Placebo and Zolpidem Tartrate Extended Release for the Treatment of Older Adults With Insomnia Disorder: A Phase 3 Randomized Clinical Trial.

Importance: Insomnia disorder is prevalent and associated with health risks in older adults; however, efficacy and safety issues with existing treatments create significant unmet needs in this patient population.

Objective: To compare treatment with the orexin receptor antagonist lemborexant with placebo and zolpidem tartrate extended release in participants with insomnia disorder.

Design, Setting, And Participants: The Study of the Efficacy and Safety of Lemborexant in Subjects 55 Years and Older With Insomnia Disorder (SUNRISE 1) clinical trial was a global randomized double-blind parallel-group placebo-controlled active-comparator phase 3 study conducted at 67 sites in North America and Europe from May 31, 2016, to January 30, 2018.

A novel forehead temperature-regulating device for insomnia: a randomized clinical trial.

Study Objectives: Insomnia is one of the most common disorders in the general population. Hypnotic medications are efficacious, but their use is limited by adverse events (AEs). This study evaluated the safety and efficacy of a novel forehead temperature-regulating device that delivers frontal cerebral thermal therapy (maintained at 14-16°C, equivalent to 57-61°F) for the treatment of insomnia.

Lemborexant, A Dual Orexin Receptor Antagonist (DORA) for the Treatment of Insomnia Disorder: Results From a Bayesian, Adaptive, Randomized, Double-Blind, Placebo-Controlled Study.

Study Objectives: To identify dose(s) of lemborexant that maximize insomnia treatment efficacy while minimizing next-morning residual sleepiness and evaluate lemborexant effects on polysomnography (PSG) measures (sleep efficiency [SE], latency to persistent sleep [LPS], and wake after sleep onset [WASO]) at the beginning and end of treatment.

Methods: Adults and elderly subjects with insomnia disorder per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition were enrolled in a multicenter, randomized, double-blind, placebo-controlled, Bayesian, adaptive, parallel-group study, receiving lemborexant (1, 2.5, 5, 10, 15, 25 mg) or placebo for 15 nights.

Pharmacodynamic effects of suvorexant and zolpidem on EEG during sleep in healthy subjects.

The objective of this study was to evaluate sleep electrophysiology in healthy subjects after bedtime administration of therapeutic doses of two insomnia treatments - the orexin receptor antagonist suvorexant or the GABAergic agonist zolpidem. Eighteen healthy men received single bedtime doses of suvorexant 20mg, zolpidem 10mg, or placebo in a double-blinded, randomized, balanced 3-period crossover study. EEG power spectral densities during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep were recorded in a polysomnography (PSG) laboratory using a 19-lead EEG recording array.

Pharmacokinetics, pharmacodynamics and safety of CEP-26401, a high-affinity histamine-3 receptor antagonist, following single and multiple dosing in healthy subjects.

CEP-26401 is a novel orally active, brain-penetrant, high-affinity histamine H3 receptor (H3R) antagonist, with potential therapeutic utility in cognition enhancement. Two randomized, double-blind, placebo-controlled dose escalation studies with single (0.02 to 5 mg) or multiple administration (0.

A randomized, double-blind, single-dose, placebo-controlled, multicenter, polysomnographic study of gabapentin in transient insomnia induced by sleep phase advance.

Study Objectives: To evaluate the effects of single doses of gabapentin 250 and 500 mg on polysomnographic (PSG) and participant-reported sleep measures in a 5-h phase advance insomnia model.

Methods: Adults reporting occasional disturbed sleep received gabapentin 500 mg (n = 125), 250 mg (n = 125), or placebo (n = 127) 30 min prior to bedtime and were in bed from 17:00 to 01:00, ∼5 h before their habitual bedtime. Sleep was assessed by PSG, post-sleep questionnaire, and the Karolinska Sleep Diary (KSD).

Efavirenz modulation of sleep spindles and sleep spectral profile.

Non-nucleoside reverse transcriptase inhibitors are important antiretroviral agents for the treatment of human immunodeficiency virus. Some non-nucleoside reverse transcriptase inhibitors, in particular efavirenz, have prominent effects on sleep, cognition and psychiatric variables that limit their tolerability. To avoid confounds due to drug-drug and drug-disease interactions, we assessed the effects of efavirenz in healthy volunteers on sleep, cognition and psychological endpoints during the first week of treatment.

Nonrestorative sleep as a distinct component of insomnia.

Study Objectives: Explore characteristics of nonrestorative sleep (NRS) in prospectively defined subgroups of individuals with NRS symptoms, investigate whether NRS can occur independently of difficulties initiating and maintaining sleep (DIS/DMS), and determine its effect on waking function.

Design: Cross-sectional and longitudinal population-based study comparing patterns of daytime symptoms, and their persistence, in cohorts of subjects with NRS symptoms grouped according to presence or absence of DIS and DMS.

Setting: 28 sleep centers in the US.

Efficacy and safety of doxepin 1 mg, 3 mg, and 6 mg in elderly patients with primary insomnia: a randomized, double-blind, placebo-controlled crossover study.

Objectives: Evaluate efficacy and safety of the histamine-H1 antagonist doxepin at doses of 1 mg, 3 mg, and 6 mg in elderly adults with primary insomnia.

Design: A randomized, double-blind, placebo-controlled, crossover design was used in this population of elderly adults with primary insomnia (DSM-IV). Each treatment period consisted of 2 polysomnographic (PSG) assessment nights with a 5- or 12-day drug-free interval between periods.

Daytime pharmacodynamic and pharmacokinetic evaluation of low-dose sublingual transmucosal zolpidem hemitartrate.

Objectives: Buffered low-dose sublingual transmucosal zolpidem lozenge hemitartrate (ST zolpidem) is being developed for the treatment of middle-of-the-night insomnia. The objective of this double-blind placebo-controlled cross-over study (n = 24) was to evaluate the pharmacokinetics (PK) and daytime-sedative profile of 1.0, 1.

Efficacy of the selective extrasynaptic GABA A agonist, gaboxadol, in a model of transient insomnia: a randomized, controlled clinical trial.

Objective: The hypnotic efficacy of gaboxadol, a selective extrasynaptic GABA A agonist (SEGA), was evaluated in a phase-advance model of transient insomnia.

Methods: Healthy subjects (18-64 years) completed a randomized, double-blind, parallel group study in which the sleep period was advanced 4h from habitual sleep time. Polysomnographic (PSG) and self-reported sleep measures were used to compare gaboxadol 10mg (N =271) and 15 mg (N =274) versus placebo (N =277).

Evaluation of an ambulatory system for the quantification of cough frequency in patients with chronic obstructive pulmonary disease.

Background: To date, methods used to assess cough have been primarily subjective, and only broadly reflect the impact of chronic cough and/or chronic cough therapies on quality of life. Objective assessment of cough has been attempted, but early techniques were neither ambulatory nor feasible for long-term data collection. We evaluated a novel ambulatory cardio-respiratory monitoring system with an integrated unidirectional, contact microphone, and report here the results from a study of patients with COPD who were videotaped in a quasi-controlled environment for 24 continuous hours while wearing the ambulatory system.

The efficacy and safety of the melatonin agonist beta-methyl-6-chloromelatonin in primary insomnia: a randomized, placebo-controlled, crossover clinical trial.

Background: While melatonin agonists are known to regulate circadian sleep rhythms, it is not clear whether melatonin agonists have a direct soporific effect. It has been suggested that melatonin's soporific effect is secondary to its ability to induce hypothermia. beta-Methyl-6-chloromelatonin is a high-affinity melatonin receptor agonist that is not associated with hypothermia.