Dose-finding Study Assessing the Efficacy, Safety, and Pharmacokinetics of Daridorexant in Subjects Aged 10 to < 18 Years With Insomnia Disorder

Inclusion criteria

• Signed and dated informed consent form (ICF) from the caregiver, i.e., parent/legal guardian prior to any study mandated procedure, or as per local regulation.
• Written assent must be obtained from subjects of the appropriate age who can give assent, as determined by the caregiver and local regulation or institutional review boards / independent ethics committees.
• Male or female subjects aged ≥ 10 and < 18 years at the time of signing the ICF.
• Chronic insomnia disorder in accordance with International Classification of Sleep Disorders, 3rd edition (ICSD-3) or insomnia disorder in accordance with Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria at Screening, as supported by statements from the child and/or the caregiver:

• Difficulty initiating or maintaining sleep, or early morning awakening with inability to return to sleep,
• Sleep difficulty has been present for at least 3 months prior to Screening,
• Sleep difficulty occurs at least 3 nights per week,
• Persistence of sleep difficulty, despite adequate sleep hygiene or non-pharmacological therapy,
• The sleep problem occurs despite adequate age appropriate time and opportunity for sleep,
• The sleep problem is not due to the direct pharmacological effects of any concomitant medication (e.g., amphetamines, selective serotonin reuptake inhibitors) as per investigator judgment,
• Self-report or caregiver report of poor sleep quality and/or quantity impacting the daytime performance of the subject,
• Sleep Disturbance Scale for Children score > 16 on the Difficulty Initiating or Maintaining Sleep domain at Screening.
• Adolescent of Child-Bearing Potential:

• Negative serum pregnancy test at Screening and a negative urine pregnancy test at Randomization.
• Agreement to undertake urine pregnancy tests during the study, as per the schedule of activities and up to 5 days after study treatment discontinuation.
• Agreement to use an acceptable effective method of contraception from Screening up to 5 days after study treatment discontinuation.
• Inclusion criteria applicable only to a subset of children with insomnia and comorbid neurodevelopmental disorder (NDD): Must have a documented history of NDD (including autism spectrum disorder or attention deficit hyperactivity disorder) according to DSM-5 criteria, as confirmed by review of medical records, at Screening. Use of central nervous system (CNS) stimulants is allowed if started at least 4 weeks prior to Screening, is stable, and is expected to remain stable during the study until End-of-Treatment. CNS stimulants are recommended to be taken in the morning.

Exclusion criteria

• Body weight < 25 kg.
• Daytime napping ≥ 1 h per day on at least 3 weekdays per week during the 3 months prior to Screening.
• Any lifetime history of sleep-related breathing disorders such as obstructive sleep apnea, based on the subject's medical records. Note: a subject whose breathing disorder has been treated by tonsillectomy/ adenoidectomy remains eligible.
• Any other diagnosed sleep-wake disorder as defined in DSM-5 or ICSD-3 (e.g., restless legs syndrome, circadian rhythm sleep wake disorder, parasomnias, narcolepsy) at Screening.
• Any of the following conditions related to suicidality:

• Any suicidal ideation with intent, with or without a plan at Screening, i.e., answering "Yes" to questions 4 or 5 on the suicidal ideation section of the lifetime (Visit 1) and visit (Visit 2) version of the Columbia Suicide Severity Rating Scale© (C-SSRS©). Participants who answer "yes" to any of these questions must be referred to the investigator for follow-up evaluation.
• History of suicide attempt on the suicidal behavior section of the lifetime version of the C-SSRS© at Visit 1.
• Any acute or unstable significant medical condition (e.g., seizure disorder, bipolar disorder, schizophrenia), hematology/biochemistry test results, and/or electrocardiogram results deviating from the normal ranges to a clinically relevant extent that would preclude participation in the study or could prevent the subject from complying with study requirements, as per investigator judgement.
• Cognitive behavior therapy for any indication is allowed only if it has been started at least 1 month prior to Visit 2 and is kept stable throughout the study.