Dataset Information

On-the-road driving performance the morning after bedtime administration of lemborexant in healthy adult and elderly volunteers.

ABSTRACT: STUDY OBJECTIVES:To assess potential effects of lemborexant on next-morning driving performance in adult and elderly healthy volunteers. METHODS:Randomized, double-blind, double-dummy, placebo and active-controlled, four period incomplete crossover study in 48 healthy volunteers (22 females), 23-78 years old. Participants were treated at bedtime for eight consecutive nights with two of three dose levels of lemborexant (2.5, 5, or 10 mg), zopiclone 7.5 mg (on the first and last night with placebo on intervening nights), or placebo. Driving performance was assessed in the morning on days 2 and 9 using a standardized highway driving test in normal traffic, measuring standard deviation of lateral position (SDLP). Drug-placebo differences in SDLP >2.4 cm were considered to reflect clinically meaningful driving impairment. RESULTS:Mean drug-placebo differences in SDLP following lemborexant 2.5, 5, and 10 mg on days 2 and 9 were 0.74 cm or less. The upper bound of the 95% confidence intervals (CIs) for lemborexant treatment groups were all below 2.4 cm and the 95% CIs included zero, indicating that the effects were neither clinically meaningful nor statistically significant. Symmetry analysis further supported the lack of clinically meaningful impairment with lemborexant. CONCLUSIONS:When assessed starting ~9 h after lemborexant administration at bedtime the previous night, there was no statistically significant or clinically meaningful effect on driving performance in healthy adults and elderly, as assessed by either mean differences in SDLP relative to placebo or symmetry analysis. In this study, lemborexant at doses up to 10 mg was well-tolerated. CLINICAL TRIAL REGISTRATION:clinicaltrials.gov, NCT02583451. https://clinicaltrials.gov/ct2/show/NCT02583451.

SUBMITTER: Vermeeren A

PROVIDER: S-EPMC6448281 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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On-the-road driving performance the morning after bedtime administration of lemborexant in healthy adult and elderly volunteers.

Vermeeren Annemiek A Jongen Stefan S Murphy Patricia P Moline Margaret M Filippov Gleb G Pinner Kate K Perdomo Carlos C Landry Ishani I Majid Oneeb O Van Oers Anita C M ACM Van Leeuwen Cees J CJ Ramaekers Johannes G JG Vuurman Eric F P M EFPM

Sleep 20190401 4

<h4>Study objectives</h4>To assess potential effects of lemborexant on next-morning driving performance in adult and elderly healthy volunteers.<h4>Methods</h4>Randomized, double-blind, double-dummy, placebo and active-controlled, four period incomplete crossover study in 48 healthy volunteers (22 females), 23-78 years old. Participants were treated at bedtime for eight consecutive nights with two of three dose levels of lemborexant (2.5, 5, or 10 mg), zopiclone 7.5 mg (on the first and last nig ...[more]

PMID: 30597112

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Project description:BACKGROUND AND OBJECTIVES: The combination of cromolyn and ibuprofen is being investigated as a treatment for early Alzheimer's disease (AD). This study investigated the pharmacokinetics, safety, and tolerability of cromolyn and ibuprofen co-administration in healthy elderly adult volunteers.MethodsIn this open-labeled study, 26 subjects, aged 55-75 years, received co-administration of inhaled cromolyn (single dose 17.1 mg; double dose 34.2 mg total) and oral ibuprofen (single dose 10 mg; double dose 20 mg total). Blood sampling was performed for 6 h after co-administration in all subjects; cerebrospinal fluid (CSF) was collected in three to four subjects per cohort for 4 h following co-administration. Safety parameters, including adverse events (AEs), were monitored throughout the study.ResultsFor cromolyn, the mean (±SD) maximum observed concentration (C max) in plasma was 46.69 ± 32.97 and 96.75 ± 46.22 ng/ml after single- and double-dose inhalation, respectively [time to C max (t max) ~22 min for each; terminal elimination half-life (t ½) ~1.8 h for each]. For ibuprofen, the plasma C max was 1090.98 ± 474.64 ng/ml and 2062.96 ± 655.13 ng/ml after single- and double-dose oral administration, respectively (t max ~1.6-1.8 h; t ½ ~1.9 h for each). For cromolyn, the CSF C max was 0.24 ± 0.08 ng/ml at 3.72 ± 0.70 h after single-dose administration and 0.34 ± 0.17 ng/ml at 3.45 ± 0.95 h after double-dose administration, and for ibuprofen, the CSF C max was 3.94 ± 1.29 ng/ml at 2.55 ± 0.96 h after single-dose administration and 8.93 ± 3.29 ng/ml at 3.15 ± 1.05 h after double-dose administration. Three (12%) subjects reported mild or moderate AEs which were unlikely to be related to study drug.ConclusionsThe combination of cromolyn and ibuprofen was safe and well tolerated. The concentrations of cromolyn and ibuprofen observed in the CSF are considered sufficient to titrate the estimated daily amyloid production and the associated inflammatory response in patients with AD.

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Dataset Information

On-the-road driving performance the morning after bedtime administration of lemborexant in healthy adult and elderly volunteers.

Publications

On-the-road driving performance the morning after bedtime administration of lemborexant in healthy adult and elderly volunteers.

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