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This paper describes the first controlled study to investigate the efficacy and safety of daridorexant, a dual orexin receptor antagonist, in children and adolescents with or without comorbid neurodevelopmental disorders, allowing its evaluation in a broad paediatric population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>This multicentre, double-blind, randomised, placebo-controlled, parallel-group, dose-finding Phase 2 trial includes male and female participants aged \u226510\u2009to &lt;18 years meeting the diagnosis of insomnia disorder as per Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) or International Classification of Sleep Disorders, Third Edition (ICSD-3) criteria. The study population is stratified into three groups: those with a known diagnosis of autism spectrum disorder (ASD) or attention-deficit hyperactivity disorder (ADHD); those without a diagnosis of ASD\/ADHD but who meet the definition of \u2018subthreshold ASD\u2019 or \u2018subthreshold ADHD\u2019; those with neither diagnosed ASD\/ADHD nor \u2018subthreshold\u2019 ASD\/ADHD. Study participants are randomised 1:1:1:1 to daridorexant 10\u2009mg, 25\u2009mg, 50\u2009mg or placebo for at least 14 days. The change from baseline to Day 1 in total sleep time, measured by polysomnography, is the primary endpoint used to characterise the dose-response relationship of daridorexant in paediatric subjects with insomnia disorder. The study also assesses the safety, tolerability, pharmacokinetics, palatability and acceptability of daridorexant.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>This study has been approved by the respective health authorities and institutional review boards\/independent ethics committees for each participating site and country and is conducted in accordance with the Declaration of Helsinki. Ethics approval has been obtained for each participating country\/site. Regardless of the outcomes, the results will be published in an international peer-reviewed scientific journal.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT05423717\">NCT05423717<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-099888","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T14:10:17Z","timestamp":1775484617000},"page":"e099888","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Daridorexant in children and adolescents with insomnia disorder: study protocol for a multicentre randomised controlled trial"],"prefix":"10.1136","volume":"16","clinical-trial-number":[{"clinical-trial-number":"nct05423717","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05423717","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05423717","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8996-1811","authenticated-orcid":false,"given":"Preciosa","family":"Coloma","sequence":"first","affiliation":[{"name":"Global Clinical Development, Idorsia Pharmaceuticals Ltd, Allschwil, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Coury","sequence":"additional","affiliation":[{"name":"Developmental & Behavioral Pediatrics, Nationwide Children\u2019s Hospital, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Wernette","sequence":"additional","affiliation":[{"name":"Global Clinical Development, Idorsia Pharmaceuticals Ltd, Allschwil, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicki","family":"Beevers","sequence":"additional","affiliation":[{"name":"The Sleep Charity, Doncaster, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Dubois","sequence":"additional","affiliation":[{"name":"Global Clinical Development, Idorsia Pharmaceuticals Ltd, Allschwil, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Di Marco","sequence":"additional","affiliation":[{"name":"Global Clinical Development, Idorsia Pharmaceuticals Ltd, Allschwil, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozan Taylan","family":"Dursun","sequence":"additional","affiliation":[{"name":"Global Clinical Development, Idorsia Pharmaceuticals Ltd, Allschwil, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliviero","family":"Bruni","sequence":"additional","affiliation":[{"name":"Department of Developmental and Social Psychology, Sapienza University, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,4,6]]},"reference":[{"key":"2026040607100662000_16.4.e099888.1","unstructured":"American Psychiatric Association . 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