Dataset Information

Respiratory safety of lemborexant in healthy adult and elderly subjects with mild obstructive sleep apnea: A randomized, double-blind, placebo-controlled, crossover study.

ABSTRACT: Lemborexant is a dual orexin receptor antagonist indicated for the treatment of adult and elderly individuals with insomnia. Some current pharmacologic treatments for insomnia cause respiratory depression, a serious safety concern, particularly for individuals with obstructive sleep apnea (OSA). This phase 1, randomized, double-blind, placebo-controlled, two-period crossover study examined respiratory safety parameters in individuals with mild OSA following treatment with lemborexant. Participants (n = 39) were randomized to one of two treatment sequences, including placebo and lemborexant 10 mg. Each treatment period lasted 8 days and was separated by a washout of at least 14 days. Following single or multiple doses, there were no significant differences in mean apnea-hypopnea index for lemborexant 10 mg versus placebo (least squares mean [LSM] difference [95% confidence interval {CI}]: day 1, -0.03 [-2.22, 2.17]; day 8, -0.06 [-1.95, 1.83]) or peripheral capillary oxygen saturation during sleep (LSM difference [95% CI]: day 1, 0.07 [-0.31, 0.46]; day 8, 0.25 [-0.11, 0.61]). There were no significant differences versus placebo for the percentage of total sleep time during which peripheral capillary oxygen saturation was <80% (LSM difference [95% CI]: day 1, 0.002 [-0.019, 0.023]; day 8, 0.006 [-0.015, 0.026]), <85% (LSM difference [95% CI]: day 1, 0.067 [-0.124, 0.258]; day 8, 0.056 [-0.117, 0.228]) or <90% (LSM difference [95% CI]: day 1, 0.312 [-0.558, 1.181]; day 8, 0.088 [-0.431, 0.607]). The incidence of treatment-emergent adverse events was low and similar for lemborexant and placebo. Lemborexant demonstrated respiratory safety in this study population and was well tolerated.

SUBMITTER: Cheng JY

PROVIDER: S-EPMC7507183 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Respiratory safety of lemborexant in healthy adult and elderly subjects with mild obstructive sleep apnea: A randomized, double-blind, placebo-controlled, crossover study.

Cheng Jocelyn Y JY Filippov Gleb G Moline Margaret M Zammit Gary K GK Bsharat Mohammad M Hall Nancy N

Journal of sleep research 20200318 4

Lemborexant is a dual orexin receptor antagonist indicated for the treatment of adult and elderly individuals with insomnia. Some current pharmacologic treatments for insomnia cause respiratory depression, a serious safety concern, particularly for individuals with obstructive sleep apnea (OSA). This phase 1, randomized, double-blind, placebo-controlled, two-period crossover study examined respiratory safety parameters in individuals with mild OSA following treatment with lemborexant. Participan ...[more]

PMID: 32187781

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Project description:Study objectivesObstructive sleep apnea is associated with neurobehavioral dysfunction, but the relationship between disease severity as measured by the apnea-hypopnea index and neurobehavioral morbidity is unclear. The objective of our study is to compare the neurobehavioral morbidity of mild sleep-disordered breathing versus obstructive sleep apnea.MethodsChildren 3-12 years old recruited for mild sleep-disordered breathing (snoring with obstructive apnea-hypopnea index < 3) into the Pediatric Adenotonsillectomy Trial for Snoring were compared to children 5-9 years old recruited for obstructive sleep apnea (obstructive apnea-hypopnea 2-30) into the Childhood Adenotonsillectomy Trial. Baseline demographic, polysomnographic, and neurobehavioral outcomes were compared using univariable and multivariable analysis.ResultsThe sample included 453 participants with obstructive sleep apnea (median obstructive apnea-hypopnea index 5.7) and 459 participants with mild sleep-disordered breathing (median obstructive apnea-hypopnea index 0.5). By polysomnography, participants with obstructive sleep apnea had poorer sleep efficiency and more arousals. Children with mild sleep-disordered breathing had more abnormal executive function scores (adjusted odds ratio 1.96, 95% CI 1.30-2.94) compared to children with obstructive sleep apnea. There were also elevated Conners scores for inattention (adjusted odds ratio 3.16, CI 1.98-5.02) and hyperactivity (adjusted odds ratio 2.82, CI 1.83-4.34) in children recruited for mild sleep-disordered breathing.ConclusionsAbnormal executive function, inattention, and hyperactivity were more common in symptomatic children recruited into a trial for mild sleep-disordered breathing compared to children recruited into a trial for obstructive sleep apnea. Young, snoring children with only minimally elevated apnea-hypopnea levels may still be at risk for deficits in executive function and attention.Trial registrationPediatric Adenotonsillectomy for Snoring (PATS), NCT02562040; Childhood Adenotonsillectomy Trial (CHAT), NCT00560859.

Project description:Obstructive sleep apnea (OSA) is prevalent in obese subjects. Plasma adiponectin level in obese subjects is decreased. Whether reduced adiponectin level is associated with OSA is unknown. Participants without a previous diagnosis of OSA or who have not been treated with continuous positive airway pressure were enrolled and parameters of interest were collected. Polysomnography was performed to evaluate the presence of OSA and the severity of OSA as indexed by the apnea-hypopnea index (AHI). Between-group differences were analyzed. Pearson correlation analysis was used to evaluate the association between body mass index (BMI) with plasma levels of adiponectin and C-reactive protein (CRP) and AHI; and the association between plasma adiponectin level with CRP and AHI was also evaluated. Logistic regression analysis was conducted to evaluate the association between per 1-SD standardized decrease of plasma adiponectin level and the prevalence of OSA using stepwise adjustment models. A total of 486 participants were enrolled and the mean BMI was 26.9 ± 6.2 kg/m with obesity prevalence of 28%; and the mean AHI was 12.6 ± 8.9 per sleep hour with OSA prevalence of 42%. The mean adiponectin level was 18.4 ± 10.6 μg/mL. Compared with the nonobese group, participants in the obese group had higher BMI, neck girth, waist circumference, and AHI (P < .05 for all comparisons). The prevalence of OSA (51% vs 37%) and the proportion of moderate OSA (49% vs 42%) were also significantly higher, while adiponectin level (14.6 ± 8.7 μg/mL vs 20.7 ± 10.5 μg/mL) was significantly lower. In the obese group, plasma adiponectin level was decreased gradually with the increasing severity of OSA, which was not observed in the nonobese group. BMI was negatively correlated with adiponectin while positively correlated with CRP and AHI; and adiponectin was negatively correlated with both CRP and AHI. After adjusted for covariates including BMI and waist circumference, adiponectin remained significantly associated with OSA prevalence with odds ratio of 1.20 (95% confidence interval 1.12-1.65). In summary, our preliminary study suggests that in obese subjects, plasma adiponectin level is associated with the prevalence of OSA.

Dataset Information

Respiratory safety of lemborexant in healthy adult and elderly subjects with mild obstructive sleep apnea: A randomized, double-blind, placebo-controlled, crossover study.

Publications

Respiratory safety of lemborexant in healthy adult and elderly subjects with mild obstructive sleep apnea: A randomized, double-blind, placebo-controlled, crossover study.

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