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

Study Overview
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Brief Summary
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This study assesses the efficacy, safety, and pharmacokinetics of multiple-dose oral administration of daridorexant in pediatric subjects aged 10 to < 18 years with insomnia disorder.

Official Title
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Multi-center, Double-blind, Randomized, Placebo-controlled, Parallel-group, Polysomnography, Dose-finding Study Assessing the Efficacy, Safety, and Pharmacokinetics of Multiple-dose Oral Administration of Daridorexant in Pediatric Subjects Aged 10 to < 18 Years With Insomnia Disorder

Conditions
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Insomnia

Intervention / Treatment
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* Drug: Daridorexant 10 mg
* Drug: Daridorexant 25 mg
* Drug: Daridorexant 50 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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 (IRBs) / independent ethics committees (IECs). 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 (ICSD), 3rd edition or insomnia disorder in accordance with 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 (SDSC) score > 16 on the Difficulty Initiating or Maintaining Sleep domain at Screening. Adolescent of Child-Bearing Potential (AoCBP): 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: Must have a documented history of NDD (including ASD or ADHD) according to DSM-5 criteria, as confirmed by review of medical records, at Screening. Use of CNS stimulants is allowed if started at least 4 weeks prior to Screening, stable and expected to remain stable during the study until EOT. 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 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, ECG 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 (CBT) 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.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Daridorexant 10 mg<br> | Drug: Daridorexant 10 mg<br>* Daridorexant will be taken orally, once daily in the evening during the treatment period.<br>|
| Experimental: Daridorexant 25 mg<br> | Drug: Daridorexant 25 mg<br>* Daridorexant will be taken orally, once daily in the evening during the treatment period.<br>|
| Experimental: Daridorexant 50 mg<br> | Drug: Daridorexant 50 mg<br>* Daridorexant will be taken orally, once daily in the evening during the treatment period.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo will be taken orally, once daily in the evening during the treatment period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to Day 1 in Total Sleep Time (TST) as measured by polysomnography (PSG). | Baseline is defined as the mean of the 2 PSG nights during the screening period. | PSG will be performed on 2 nights during the screening period and on Day 1 of the treatment period (total duration: 3 days). |