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5 Effect of daridorexant on wakefulness throughout the night and morning sleepiness in patients with insomnia
IntroductionReducing wakefulness throughout the night without residual effects the next morning are essential characteristics for drugs for chronic insomnia disorder. Here we examine the effect of daridorexant on wakefulness throughout the night and next-morning sleepiness.MethodsData from 930 patients with insomnia disorder randomized to daridorexant 50 mg, 25 mg or placebo for 3 months were analyzed. Polysomnography-determined WASO by quarter of the night (Q1 to Q4) at Month (M)1 and M3 of treatment, and morning sleepiness upon awakening by a visual analogue scale (VAS).were assessed.ResultsDecreases in WASO in Q2-4 of the night were numerically larger in both daridorexant dose groups versus placebo.. At M1 and M3, both daridorexant 50mg and 25mg reduced WASO across Q2-4vs placebo.VAS morning sleepiness scores increased (i.e. improved) from Day 1 of treatment in all groups and continued to improve as treatment continued, with larger effects seen with daridorexant 50 mg and 25 mg than placebo.ConclusionIn patients with insomniadisorder, daridorexant reduces wakefulness throughout the entire night while decreasing morning sleepiness upon awakening.FundingIdorsia Pharmaceuticals LtdOriginally presented at Sleep Europe 2024, Seville, Spain, P1213james.khoo@idorsia.com
Journal Article
0407 Impact of Lemborexant on Daytime Ratings of Sleepiness/Alertness in Subjects with Insomnia Disorder and Baseline Sleepiness
Introduction Since the use of sleep-promoting drugs can also lead to residual morning sleepiness, it is important to determine if a new hypnotic is associated with such a carryover effect of treatment. To this end, an assessment of sleepiness/alertness was included in lemborexant (LEM) phase 3 studies. LEM is a competitive dual orexin receptor antagonist approved in several countries for the treatment of adults with insomnia. This post-hoc analysis of Study 304 (E2006-G000-304; NCT02783729) assessed the impact of LEM on morning sleepiness/alertness in subjects who reported at least mild/moderate morning sleepiness at baseline. Methods Study 304 was a randomized controlled study in adults ≥55y with insomnia disorder (N=1006). Subjects received bedtime doses of placebo (PBO), LEM 5mg (LEM5), LEM 10mg (LEM10), or zolpidem tartrate extended release 6.25 mg (not reported here) for 1 month. A daily Sleep Diary assessed morning sleepiness, within 90 min of waketime, with the question “How alert/sleepy do you feel this morning?” rated from 1 (extremely sleepy) to 9 (extremely alert). Scores were averaged over 7-day periods for baseline (single-blind run-in) and first and last 7 days of treatment. Chi-square tests were used to compare the shift from sleepy (≤3) to more alert (>3) between PBO and treatment groups. Results At baseline, 59/203 (29.1%), 66/261 (25.3%), and 79/265 (29.8%) of the PBO, LEM5, and LEM10 subjects reported a score ≤3, indicating at least mild/moderate morning sleepiness. At the end of 1 month of treatment, 37/57 (64.9%) of the PBO subjects rated themselves as less sleepy and more alert (>3), compared with 50/64 (78.1%; P=0.11) LEM5- and 58/76 (76.3%; P=0.15) LEM10-treated subjects. Conclusion In this study, ~28% of subjects reported morning sleepiness at baseline. More subjects who reported sleepiness at baseline and received LEM reported improved morning alertness during the last week of treatment compared with PBO subjects. These data are concordant with previous findings of a lack of effect of LEM on tasks requiring alertness in the morning. Support (if any) Eisai Inc.
Journal Article
0350 Daridorexant in patients with insomnia disorder: number needed to treat, number needed to harm & likelihood to be helped or harmed
Introduction Patients with insomnia disorder have difficulty initiating or maintaining sleep and have impaired daytime functioning. Daridorexant is a dual orexin receptor antagonist approved for the treatment of insomnia. This analysis reports the number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH) with daridorexant 25 mg or 50 mg versus placebo over 3 months. Methods Phase 3 data from one of two pivotal trials (N=930: randomized 1:1:1 to daridorexant 25 mg, 50 mg, or placebo) were used to calculate NNT, NNH, and LHH. For the NNT analysis, wakefulness after sleep onset, latency to persistent sleep, self-reported total sleep time, the Insomnia Daytime Symptoms and Impacts Questionnaire, and the Insomnia Severity Index were explored. NNT was assessed using a range of clinically meaningful thresholds (CMTs), from minimal clinical improvement (MiCI) to marked clinical improvement. NNH analysis was performed on adverse events (AEs) occurring in >1% of participants in any treatment arm. LHH values were calculated for all NNT outcomes using the NNH estimates for somnolence and fatigue AEs. Results At Month 1 and 3, NNT values at MiCI thresholds for daridorexant 50 mg ranged from 5–9 and 6–12, respectively, and were all statistically significantly different versus placebo, indicating a good therapeutic response. Daridorexant 50 mg had at least one NNT < 10 for CMTs across all outcomes. NNTs at MiCI thresholds for daridorexant 25 mg ranged between 7–328 and 8–1666. NNH values for daridorexant 25 and 50 mg were negative or not significantly different from placebo, confirming a good tolerability profile. For a somnolence AE, LHH values ranged from 83.3–200 for daridorexant 50 mg versus placebo. For a fatigue AE, LHH ranged from 4.3–10.2. Conclusion Daridorexant 25 mg and 50 mg both have a positive benefit-risk ratio compared with placebo over 3 months. Furthermore, daridorexant 50 mg showed ‘good’ NNT values (i.e. NNT < 10) over all efficacy endpoints in relation to the CMTs. NNH results confirmed the good tolerability profile of both doses. Support (if any) Funded by Idorsia Pharmaceutical Ltd.
Journal Article
0355 Insomnia Identity’s Association with Insomnia Problem Chronicity and Treatment History
Introduction Insomnia identity is defined as the “conviction that one has insomnia” or self-identifies as an “insomniac.” The present study sought to evaluate whether insomnia chronicity and past insomnia treatment predicts whether someone identifies as an “insomniac” in a large sample of adult participants with sleep complaints. Methods This study utilized a cross-sectional group design in an archival/community dataset that was collected in the Philadelphia area. The data were drawn from 2,950 adults between 18 and 90 years of age who specifically reported problems with total sleep time (TST). All participants answered questions regarding age of problem onset, insomnia treatment history, and insomnia identity (“Do you think of yourself as an ‘insomniac’?”). Results Of the 2,863 participants included in this analysis (Mage=53.5±10.7; 76.6% female; 91.2% White), 45.1% identified as an “insomniac.” Binary logistic regression was used to examine whether TST problem chronicity (Myears=12.3±10.0) and treatment history (36.6%) were associated with the likelihood of identifying as an “insomniac.” Outliers were removed and assumptions were met. The model was statistically significant X2=(2, N=2,863)=172.4, p< 0.001, suggesting that it could distinguish between those who did and did not identify as an “insomniac.” The model correctly classified 60.9% of cases. TST problem chronicity (OR=1.04, 95% CI [1.027, 1.043]) and treatment history (OR=0.51, 95% CI [0.435, 0.596]) significantly contributed to the model. Conclusion Participants were 4% more likely to identify as an “insomniac” with each year of TST problem chronicity and were 49% less likely to identify as an “insomniac” if they engaged in prior insomnia treatment. Findings align with a recent study that also found that individuals with insomnia identity reported longer insomnia chronicity and that individuals with and without insomnia identity seek insomnia treatment. Future analyses should consider additional variables including insomnia frequency (days per week), severity (e.g., total nocturnal wakefulness [TWT]), daytime symptomatology, perceived sleep need, and demographic factors including age, sex, and race. Support (if any) K24AG055602
Journal Article
0323 Natural Evolution of Insomnia in Major Depressive Disorders
Introduction Insomnia is a fairly common sleep disturbance affecting nearly one third of the general population. Although its predictive value for major depressive disorder (MDD) has been well documented, little is known about its role in the appearance of a first episode or in the recurrence. In this study, we examine the predictive value of insomnia symptoms in the incidence and recurrence of MDD. Methods In this longitudinal study, 2 interview waves were conducted between 2002 and 2015. The initial interviews (wave 1 [W1]) were carried out with 12,218 individuals aged ≥18 years from the general population in 8 US states. At follow-up 3 years later (wave 2 [W2]), 10,931 of the initial participants agreed to be interviewed again. Data were analyzed for the individuals who participated in both interviews (N=10,931). A diagnosis of MDD was made according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria. Insomnia symptoms were defined according to DSM-5 criteria A, C, and D for insomnia disorder. Results The 12-month prevalence of MDD was 9.5% (95% CI, 9.0%-10.0%) and 12.1% (95% CI, 11.5%-12.7%) in W1 and W2, respectively. Over the course of the study, 2.6% of participants experienced recurrence of depression (95% CI, 2.3%-2.9%). After adjusting for age, gender, race, and body mass index, participant characteristics in W1 that predicted recurrent MDD in W2 included early morning awakenings (EMA) (relative risk [RR], 3.2; 95% CI, 2.3-4.4), being dissatisfied with one’s sleep (RR, 2.8; 95% CI, 2.1-3.7), nocturnal awakenings (RR, 2.4; 95% CI, 1.8-3.2), and difficulty initiating sleep (DIS) (RR, 2.0; 95% CI, 1.5-2.9). MDD incidence was predicted by DIS (RR, 3.8; 95% CI, 2.5-5.9), being dissatisfied with one’s sleep (RR, 2.1; 95% CI, 1,4-3.2), and EMA (RR, 2.0; 95% CI, 1.2-3,2) at W1. Conclusion Insomnia symptoms appear to play an important part in predicting both the development of a first depressive episode as well as the recurrence of depression. Support (if any) Data analysis study were funded by Takeda Pharmaceutical Company.
Journal Article