{
  "abstract": "Reducing wakefulness throughout the night without residual effects the next morning are essential characteristics for drugs for chronic insomnia disorder. In Phase 3 trials, daridorexant, a dual orexin receptor antagonist, reduced wake after sleep onset (WASO) with rates of daytime somnolence similar to placebo. Here we examined,in more detail, the effect of daridorexant on wakefulness throughout the night and next-morning sleepiness.Data from 930 patients with insomnia disorder randomized to daridorexant 50 mg, 25 mg or placebo for 3 months were analyzed. Polysomnography-determined WASO by quarter of the night (QoN: Q1 to Q4) at Month (M)1 and M3 of treatment, and morning sleepiness upon awakening by a visual analogue scale were assessed.Decreases in WASO in Q2-4 of the night were numerically larger in both daridorexant dose groups versus placebo. Baseline WASO in Q1 was low in all groups and thus there were no visible changes in WASO in Q1. At M1, placebo reduced WASO evenly across QoN (Q2-4): Q2: -3.3 min, Q3: -3.7 min, Q4: -3.9 min. Daridorexant 25 mg reduced WASO by -6.2 min, -7.2 min and -7.6 min and daridorexant 50 mg reduced WASO by -8.7 min, -9.6 min, -11.3 min in Q2, Q3 and Q4, respectively. Results were similar at M3.Mean baseline VAS morning sleepiness scores were 37-38 across groups. Scores increased (i.e. improved) from Day 1 of treatment in all groups and continued to improve as treatment duration increased, with treatment numerically ranked as daridorexant 50 mg > 25 mg > placebo. Mean weekly scores at Week 4 and Week 12, increased (p values <0.05 for comparison of daridorexant 25 mg or 50 mg vs placebo at Weeks 4 and 12).In patients with insomnia disorder, daridorexant reduces wakefulness throughout the entire night including Q4, while decreasing morning sleepiness upon awakening.Funding Idorsia Pharmaceuticals",
  "authors": [
    {
      "affiliations": [
        "Idorsia Pharmaceuticals UK Ltd, London, United Kingdom"
      ],
      "name": "James Khoo"
    },
    {
      "affiliations": [
        "Centre Hospitalier Universitaire de Montpellier, France"
      ],
      "name": "Yves Dauvilliers"
    },
    {
      "affiliations": [
        "Clinilabs Drug Development Corporation, New York, USA"
      ],
      "name": "Gary Zammit"
    },
    {
      "affiliations": [
        "Idorsia Pharmaceuticals Ltd, Allschwil, Switzerland"
      ],
      "name": "Pierre-Phillippe Luyet"
    },
    {
      "affiliations": [
        "Idorsia Pharmaceuticals Ltd, Allschwil, Switzerland"
      ],
      "name": "Guy Braunstein"
    },
    {
      "affiliations": [
        "Idorsia Pharmaceuticals Ltd, Allschwil, Switzerland"
      ],
      "name": "Antonio Olivieri"
    }
  ],
  "title": "P4 Effect of daridorexant on wakefulness throughout the night and morning sleepiness in patients with insomnia disorder",
  "uid": "b54cd59b-ac97-5acb-bd96-61f4902a125c"
}