Résumé
Objective: To assess the dose-response of daridorexant, a new dual orexin
receptor antagonist, on wake after sleep onset (WASO). Methods: Elderly
(≥65 years) subjects (n = 58) with insomnia were randomly allocated (Latin
square design) to receive five treatments (5, 10, 25, and 50 mg
daridorexant and placebo) during five treatment periods, each consisting
of two treatment nights followed by a 5–12-day washout period. Main
efficacy endpoints were the absolute change from baseline in WASO
(primary) and latency to persistent sleep (LPS; secondary) to Days
1&2 (mean of two treatment nights assessed by polysomnography) in
each period. Safety and tolerability were also assessed. Results: Of 58
subjects included, 67% were female and median age was 69 years [range
65–85]). WASO and LPS were dose-dependently reduced from baseline to Days
1&2 following daridorexant administration (multiple comparison
procedure-modeling, p<0.0001 and p=0.004, respectively); reductions
were statistically significant for doses 10 mg and above compared with
placebo (WASO: –32.0, –45.1, –61.4 min; LPS: –44.9, –43.8, –45.4 min; for
10, 25, and 50 mg, respectively, p≤0.025). Treatment-emergent adverse
events were similar for daridorexant and placebo; the most frequent were
fatigue, nasopharyngitis, gait disturbance, and headache (≤7% in any
group). Conclusions: Daridorexant was well tolerated. Dose-dependent
improvements in WASO and LPS were statistically significant (dose range
10–50 mg) in elderly subjects with insomnia disorder. ClinicalTrials.gov
(NCT02841709). Classification of Evidence: This study provides Class III
evidence that for elderly subjects with insomnia, daridorexant reduced
wake after sleep onset time.