suvorexant and zopiclone

Suvorexant is a first-in-class orexin receptor antagonist for treating insomnia. There is a general concern that hypnotics may impair next-morning driving ability.. The objective of this study was to evaluate next-morning driving performance in older adults after single and repeated doses of suvorexant.. Double-blind, randomized, placebo-controlled, 4-period crossover study in 24 healthy volunteers (10 females), aged 65-80 years. Subjects were treated with suvorexant (15 and 30 mg) for eight consecutive nights, zopiclone 7.5 mg nightly on days 1 and 8, and placebo. Driving performance was assessed on days 2 and 9 (9 h after dosing) using a 1-h 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.. Driving performance as measured by SDLP was not impaired following suvorexant. Mean drug-placebo differences in SDLP following suvorexant 15 and 30 mg on day 2 and 9 were 0.6 cm or less. Their 90 % CIs were all below the threshold of 2.4 cm for clinical relevance and included zero, indicating effects were not clinically meaningful or statistically significant. Symmetry analysis showed no significant differences between the number of participants who had SDLP differences >2.4 cm and those who had SDLP differences <-2.4 cm following suvorexant.. There was no clinically meaningful residual effect of suvorexant 15 and 30 mg on next-morning driving (9 h after bedtime dosing) in healthy older adults, as assessed by mean changes in SDLP and by the number of participants on drug versus placebo that exceeded a predetermined threshold for clinically meaningful impairment.

Topics: Aged; Aged, 80 and over; Automobile Driving; Azabicyclo Compounds; Azepines; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Healthy Volunteers; Humans; Hypnotics and Sedatives; Male; Piperazines; Psychomotor Performance; Sleep Aids, Pharmaceutical; Sleep Initiation and Maintenance Disorders; Time Factors; Triazoles

To evaluate next-morning driving performance in adults younger than 65 years, after single and repeated doses of suvorexant 20 and 40 mg.. Double-blind, placebo-controlled, 4-period crossover study.. Maastricht University, The Netherlands.. 28 healthy volunteers (15 females), aged 23 to 64 years.. Suvorexant (20 and 40 mg) for 8 consecutive nights; zopiclone 7.5 mg nightly on day 1 and 8; placebo.. Performance on day 2 and 9 (9 h after dosing) using a one-hour standardized highway driving test in normal traffic, measuring standard deviation of lateral position (SDLP). Drug-placebo changes in SDLP > 2.4 cm were considered to reflect meaningful driving impairment.. Mean drug-placebo changes in SDLP following suvorexant 20 and 40 mg were 1.01 and 1.66 cm on day 2, and 0.48 and 1.31 cm on Day 9, respectively. The 90% CIs of these changes were all below 2.4 cm. Symmetry analysis showed that more subjects had SDLP changes > 2.4 cm than < -2.4 cm following suvorexant 20 and 40 mg on day 2, and following suvorexant 40 mg on day 9. Four female subjects requested that a total of 5 driving tests--all following suvorexant--stop prematurely due to self-reported somnolence.. As assessed by mean changes in standard deviation of lateral position (SDLP), there was no clinically meaningful residual effect of suvorexant in doses of 20 and 40 mg on next-morning driving (9 h after bedtime dosing) in healthy subjects < 65 years old. There may be some individuals who experience next-day effects, as suggested by individual changes in SDLP and prematurely stopped tests.. clinicaltrials.gov NCT01311882.

Topics: Adult; Automobile Driving; Azabicyclo Compounds; Azepines; Cross-Over Studies; Double-Blind Method; Female; Healthy Volunteers; Humans; Individuality; Male; Middle Aged; Netherlands; Piperazines; Psychomotor Performance; Self Report; Sleep Aids, Pharmaceutical; Sleep Stages; Triazoles; Young Adult

Topics: Animals; Arousal; Azabicyclo Compounds; Azepines; Benzodiazepines; Cognitive Behavioral Therapy; Doxepin; Dreams; Histamine Agonists; Histamine Antagonists; Humans; Hypnotics and Sedatives; Hypothalamus; Orexin Receptors; Piperazines; Piperidines; Receptors, G-Protein-Coupled; Receptors, GABA; Receptors, Histamine H3; Receptors, Neuropeptide; Sleep Initiation and Maintenance Disorders; Triazoles