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Abstract
Objective To assess the dose-response of daridorexant, a new dual orexin receptor antagonist, on wake after sleep onset (WASO).
Methods Elderly (≥65 years) participants (n = 58) with insomnia were randomly allocated (Latin square design) to receive 5 treatments (5, 10, 25, and 50 mg daridorexant and placebo) during 5 treatment periods, each consisting of 2 treatment nights followed by a 5- to 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 and 2 (mean of 2 treatment nights assessed by polysomnography) in each period. Safety and tolerability were also assessed.
Results Of 58 participants included, 67% were female, and the median age was 69 years (range 65–85 years). WASO and LPS were dose-dependently reduced from baseline to days 1 and 2 after daridorexant administration (multiple comparison procedure modeling, p < 0.0001 and p = 0.004, respectively); reductions were statistically significant for doses ≥10 mg compared with placebo (WASO: −32.0, −45.1, −61.4 minutes; LPS: −44.9, −43.8, −45.4 minutes 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 people with insomnia disorder.
ClinicalTrials.gov identifier: NCT02841709.
Classification of evidence This study provides Class I evidence that, for elderly people with insomnia, daridorexant reduced WASO.
Glossary
- AASM=
- American Academy of Sleep Medicine;
- AE=
- adverse event;
- AESI=
- adverse events of special interest;
- ALT=
- alanine aminotransferase;
- DSM-V=
- Diagnostic and Statistical Manual of Mental Disorders, Vth edition;
- DSST=
- Digit Symbol Substitution Test;
- EOT=
- end of treatment;
- FAS=
- full analysis set;
- ISB=
- Independent Safety Board;
- KSS=
- Karolinska Sleepiness Scale;
- LPS=
- latency to persistent sleep;
- LS=
- least squares;
- MCP-Mod=
- multiple comparison procedure modeling;
- PSG=
- polysomnography;
- SDS=
- Sheehan Disability Scale;
- sLSO=
- subjective latency to sleep onset;
- sTST=
- subjective total sleep time;
- sWASO=
- subjective wake after sleep onset;
- TEAE=
- treatment-emergent adverse event;
- TST=
- total sleep time;
- VAS=
- visual analog scale;
- WASO=
- wake after sleep onset
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
↵* These authors contributed equally to this work.
Patient Page, page e2287
Class of Evidence: NPub.org/coe
Podcast: NPub.org/inqgmb
- Received July 8, 2019.
- Accepted in final form January 28, 2020.
- © 2020 American Academy of Neurology
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