{
  "abstract": "Introduction Daridorexant is a dual orexin receptor antagonist approved for the treatment of adult patients with chronic insomnia. Following single-dose administration at bedtime to healthy non-elderly and elderly subjects, pharmacodynamics (PD) and safety were investigated in the middle of the night (MOTN) after forced awakening to a noise stimulus.Methods Double-blind, placebo-controlled, randomized, 3-way crossover study (placebo, 25, and 50 mg daridorexant in the evening) in 36 male and female non-elderly and elderly subjects. Four h post-bedtime administration, the auditory awakening threshold (AAT) was determined (increasing noise signal up to 100 dB). Next, the main PD endpoint postural stability (body sway) as well as basic functional mobility (Timed Up and Go (TUG) test), and cognitive function/memory using the Visual Verbal Learning Test (VVLT) were assessed. Thereafter, subjects returned to bed.Results All 36 subjects completed the study. The average AAT was approximately 60 dB across treatments with no differences between daridorexant and placebo. Body sway showed a small, dose-dependent increase vs placebo with differences in least square means (LSM) 95% confidence interval (CI) of 36.7 (2, 71) and 65.9 (31, 100) mm, for daridorexant 25 and 50 mg, respectively. The overall increased body sway was driven by non-elderly subjects,. Subjects completed the TUG test in 6–8 s across treatments, with a small, dose-dependent increase vs placebo with a difference in LSM (95% CI) of 0.14 (0.02, 0.27) and 0.47 (0.34, 0.59) s for daridorexant 25 and 50 mg, respectively. The VVLT showed minimal differences to for daridorexant 25 and 50 mg, respectively.Conclusion Following bedtime administration, daridorexant preserved the ability to respond to external noise stimuli and subjects were able to operate safely during the night.Support: Idorsia Pharmaceuticals LtdOriginally presented at Sleep Europe 2024, Seville, Spain, P1213",
  "authors": [
    {
      "affiliations": [
        "Idorsia Pharmaceuticals UK Ltd, London, United Kingdom"
      ],
      "name": "Carly Hurn"
    },
    {
      "affiliations": [
        "Idorsia Pharmaceuticals Ltd, Hegenheimermattweg , Switzerland"
      ],
      "name": "Clemens Muehlan"
    },
    {
      "affiliations": [
        "Centre for Human Drug Research, Zernikedreef , The Netherlands"
      ],
      "name": "Ingrid Koopmans"
    },
    {
      "affiliations": [
        "Idorsia Pharmaceuticals Ltd, Hegenheimermattweg , Switzerland",
        "Centre for Human Drug Research, Zernikedreef , The Netherlands"
      ],
      "name": "Massimo Magliocca"
    },
    {
      "affiliations": [
        "Idorsia Pharmaceuticals Ltd, Hegenheimermattweg , Switzerland"
      ],
      "name": "Cedric Vaillant"
    },
    {
      "affiliations": [
        "Centre for Human Drug Research, Zernikedreef , The Netherlands"
      ],
      "name": "Rob Zuiker"
    },
    {
      "affiliations": [
        "Idorsia Pharmaceuticals Ltd, Hegenheimermattweg , Switzerland"
      ],
      "name": "Jasper Dingemanse"
    }
  ],
  "title": "P13 Nighttime safety of daridorexant: response to noise stimuli, and effects on postural stability, walking and memory",
  "uid": "46b9d58e-2c54-51a0-b228-fe11c7c9a6de"
}