Evidence map›Paper›PMID 37477771›Full record

Trial reportCNS drugs2023

Number, Duration, and Distribution of Wake Bouts in Patients with Insomnia Disorder: Effect of Daridorexant and Zolpidem.

Tobias Di Marco, Thomas E Scammell, Michael Meinel, Dalma Seboek Kinter, Alexandre N Datta, Gary Zammit, Yves Dauvilliers

2 registry-linked trialsOpen access · hybridAbstract readRandomized Controlled TrialClinical Trial, Phase IIClinical Trial, Phase III
PubMed Full text at PMC Publisher
In one paragraph

Trial report in CNS drugs, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
3.3field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02839200 phase2completednot on this map

Multi-center, Double-blind, Randomized, Placebo-controlled, Active-reference, Parallel-group, Polysomnography Dose-response Study to Assess the Efficacy and Safety of ACT-541468 in Adult Subjects With Insomnia Disorder

TypeinterventionalSponsorIdorsia Pharmaceuticals Ltd.Ran2016 to 2017Enrolled360ConditionsInsomnia DisorderArmsACT-541468 5 mg, ACT-541468 10 mg, ACT-541468 25 mg, Zolpidem, Placebo 1
NCT03545191 phase3completednot on this map

Multi-center, Double-blind, Randomized, Placebo-controlled, Parallel-group, Polysomnography Study to Assess the Efficacy and Safety of ACT-541468 in Adult and Elderly Subjects With Insomnia Disorder

TypeinterventionalSponsorIdorsia Pharmaceuticals Ltd.Ran2018 to 2020Enrolled930ConditionsInsomnia DisorderArmsDaridorexant 25 mg, Daridorexant 50 mg, Placebo
3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Trial
  5. Trial
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Review
  15. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 5 institutions in 3 countries.

Tobias Di MarcoIdorsia Pharmaceuticals Ltd, Hegenheimermattweg 91, 4123, Allschwil, Switzerland. tobias.di-marco@idorsia.com.ORCID http://orcid.org/0009-0008-8973-2342
Thomas E ScammellDepartment of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA.ORCID http://orcid.org/0000-0002-7231-8558
Michael MeinelIdorsia Pharmaceuticals Ltd, Hegenheimermattweg 91, 4123, Allschwil, Switzerland.
Dalma Seboek KinterIdorsia Pharmaceuticals Ltd, Hegenheimermattweg 91, 4123, Allschwil, Switzerland.
Alexandre N DattaDepartment of Clinical Research, University of Basel, Schanzenstrasse 55, 4031, Basel, Switzerland.ORCID http://orcid.org/0000-0002-2218-8484
Gary ZammitClinilabs Drug Development Corporation, New York, NY, USA.ORCID http://orcid.org/0000-0001-8332-6687
Yves DauvilliersNational Reference Centre for Orphan Diseases, Narcolepsy-Rare hypersomnias, Sleep Unit, Department of Neurology, CHU Montpellier, Institute for Neurosciences of Montpellier INM, Univ Montpellier, INSERM, Montpellier, France.ORCID http://orcid.org/0000-0003-0683-6506
Idorsia (Switzerland) · CHUniversity of Basel · CHBeth Israel Deaconess Medical Center · USClinilabs (United States) · USInserm · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDaridorexant, a dual orexin receptor antagonist approved in early 2022, reduces wake after sleep onset without reducing the number of awakenings in patients with insomnia. The objective of this post hoc analysis was to explore the effect of daridorexant on the number, duration, and distribution of night-time wake bouts, and their correlation with daytime functioning.

methodsAdults with insomnia disorder were randomized 1:1:1:1:1:1 to placebo, zolpidem 10 mg, or daridorexant 5, 10, 25, or 50 mg in a phase II dose-finding study, and 1:1:1 to placebo or daridorexant 25 or 50 mg in a pivotal phase III study. We analyzed polysomnography data for daridorexant 25 and 50 mg, zolpidem 10 mg, and placebo groups. Polysomnography was conducted at baseline, then on Days 1/2, 15/16, and 28/29 in the phase II study, and Months 1 and 3 in the phase III study. The number, duration, and distribution of wake bouts (≥ 0.5 min) were assessed.

resultsData from 1111 patients (phase II study: daridorexant 50 mg [n = 61], zolpidem 10 mg [n = 60], placebo [n = 60]; phase III study: daridorexant 25 mg [n = 310], daridorexant 50 mg [n = 310], placebo [n = 310]) were analyzed. Long wake bouts were defined as > 6 min. Compared with placebo, daridorexant 50 mg reduced overall wake time (p < 0.05; all time points, both studies), the odds of experiencing long wake bouts (p < 0.001; Months 1 and 3, phase III study), and the cumulative duration of long wake bouts (p < 0.01; all time points, both studies). Reductions in long wake bouts were sustained through the second half of the night and correlated with improvements in daytime functioning. An increase in the cumulative duration of short wake bouts was observed with daridorexant 50 mg (p < 0.01 vs placebo, Months 1 and 3, phase III study); this was uncorrelated with daytime functioning.

conclusionDaridorexant reduced the number and duration of longer wake bouts throughout the night compared with placebo, corresponding with improved daytime functioning. CLINICAL TRIALS: Clinicaltrials.gov NCT02839200 (registered July 20, 2016), NCT03545191 (registered June 4, 2018).

Indexed as

Sleep Initiation and Maintenance DisordersAdultDouble-Blind MethodHumansImidazolesPyridinesPyrrolidinesZolpidemdaridorexantImidazolesPyridinesPyrrolidinesZolpidem

Identifiers

PMID37477771
PMCPMC10374812
OpenAlexW4384925100

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.