Dose-Response Evaluation of Daridorexant in Pediatric Insomnia: A Randomized, Double-Blind, Placebo-Controlled Polysomnography Study
- Trial ID
- 2024-513885-20-00
- Protocol
- ID-078A205
- Sponsor
- Idorsia Pharmaceuticals Ltd.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to characterize the **dose-response relationship** of daridorexant on objective total sleep time (TST) using polysomnography (PSG) in pediatric subjects with **insomnia disorder**. This is clinically relevant as it aims to determine the optimal dosing of daridorexant to improve sleep duration in children and adolescents, which is crucial for their overall health and development.
Secondary objectives include assessing the safety and tolerability of daridorexant in pediatric subjects with insomnia disorder. Evaluating these parameters is essential to ensure that the treatment is not only effective but also safe for long-term use in this vulnerable population.
Participants
The clinical trial involves a total of **81 participants** diagnosed with **insomnia disorder**. The study population comprises both male and female subjects aged between 10 and 18 years. Participants were selected based on specific inclusion criteria, including a diagnosis of chronic insomnia disorder according to the International Classification of Sleep Disorders (ICSD), 3rd edition, or the DSM-5 criteria. The trial includes a vulnerable population, as it involves pediatric subjects. Participants are required to have a Sleep Disturbance Scale for Children (SDSC) score greater than 16 in the Difficulty Initiating or Maintaining Sleep domain at screening. The study also considers lifestyle factors, such as the use of central nervous system stimulants, which are permitted if stable and initiated at least four weeks prior to screening. The trial population includes adolescents of child-bearing potential, who must adhere to specific pregnancy testing and contraception requirements. Additionally, a subset of participants with comorbid neurodevelopmental disorders, such as autism spectrum disorder or attention deficit hyperactivity disorder, is included, provided they have a documented history of such conditions.
Plans and Procedures
The clinical trial is designed as a **randomized**, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy, safety, and pharmacokinetics of multiple-dose oral administration of **daridorexant** in pediatric subjects aged 10 to less than 18 years with **insomnia disorder**. The trial aims to characterize the dose-response relationship of daridorexant on objective total sleep time using polysomnography. The study is expected to run from August 2022 to April 2025, with a maximum treatment period of 20 days for each participant.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, diagnosis of chronic insomnia disorder, and other health parameters. During the screening period, polysomnography will be performed on two nights to establish baseline sleep metrics. Following randomization, participants will receive either daridorexant or a matching placebo, administered orally in the form of film-coated tablets. The treatment period will include regular follow-up visits to monitor safety and efficacy, with polysomnography conducted on Day 1 of the treatment period to measure changes in total sleep time.
The end-of-study visit will occur after the completion of the treatment period, where final assessments will be conducted to evaluate the overall impact of the treatment. Participants are expected to be involved in the study for approximately 20 days, with conditions for early termination including adverse events, withdrawal of consent, or non-compliance with study procedures. The trial is structured to ensure rigorous data collection and analysis, adhering to ethical standards and regulatory requirements.
Treatment
The clinical trial involves the administration of **daridorexant** in various formulations to assess its efficacy, safety, and pharmacokinetics in pediatric subjects with insomnia disorder. The primary experimental medication is **QUVIVIQ 50 mg film-coated tablets**, containing the active substance **daridorexant**. These tablets are administered orally, with a maximum daily dose of 50 mg and a total maximum dose of 1000 mg over a treatment period of 20 days. The tablets have been modified for the clinical trial by changing the film coat color and removing debossing to ensure blinding. The pharmaceutical form is a film-coated tablet, and the product is manufactured by IDORSIA PHARMACEUTICALS DEUTSCHLAND GMBH.
Another experimental medication used in the trial is **QUVIVIQ 25 mg film-coated tablets**, also containing **daridorexant**. These tablets are administered orally, with a maximum daily dose of 25 mg and a total maximum dose of 500 mg over a 20-day treatment period. Similar to the 50 mg tablets, these have undergone modifications for blinding purposes. The pharmaceutical form remains a film-coated tablet, and the manufacturer is IDORSIA PHARMACEUTICALS DEUTSCHLAND GMBH.
The trial also includes a comparator treatment, **daridorexant 10 mg tablets**, which are administered orally. The maximum daily dose is 10 mg, with a total maximum dose of 200 mg over the same 20-day period. These tablets are produced by IDORSIA PHARMACEUTICALS LTD and serve as a lower-dose comparator to evaluate the dose-response relationship of **daridorexant**.
A **daridorexant matching placebo** is utilized in the study to maintain the double-blind design. The placebo is designed to match the appearance of the active medication but contains no active substance. It is used to assess the efficacy of **daridorexant** against a non-active control, ensuring that any observed effects can be attributed to the active medication rather than psychological or other non-specific effects.
Efficacy
The efficacy of the clinical trial will be assessed by evaluating the dose-response relationship of **daridorexant** on objective total sleep time (TST) in pediatric subjects with insomnia disorder. The primary endpoint for efficacy is the change from baseline to Day 1 in TST, measured in minutes, using polysomnography (PSG). PSG will be conducted on two nights during the screening period and on Day 1 of the treatment period, with the baseline defined as the mean of the two PSG nights during the screening period. This approach allows for a precise assessment of sleep improvements attributable to the treatment.
Inclusion and Exclusion Criteria
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: 1) Difficulty initiating or maintaining sleep, or early morning awakening with inability to return to sleep, 2) Sleep difficulty has been present for at least 3 months prior to Screening, 3) Sleep difficulty occurs at least 3 nights per week, 4) Persistence of sleep difficulty, despite adequate sleep hygiene or non-pharmacological therapy, 5) The sleep problem occurs despite adequate age appropriate time and opportunity for sleep, 6) 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, 7) 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): 1) Negative serum pregnancy test at Screening and a negative urine pregnancy test at Randomization. 2) Agreement to undertake urine pregnancy tests during the study, as per the schedule of activities and up to 5 days after study treatment discontinuation. 3) 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 neurodevelopmental disorder (NDD; including autism spectrum disorder [ASD] or attention deficit hyperactivity disorder [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: 1) Any suicidal ideation with intent, with or without a plan at Screening, i.e., answering "Yes" to questions 4or 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. 2) 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.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Bulgaria | Not Recruiting | 09 Aug 2022 | 15 |
 Germany | Not Recruiting | 09 Aug 2022 | 15 |
 Italy | Not Recruiting | 09 Aug 2022 | 19 |
 Spain | Not Recruiting | 09 Aug 2022 | 20 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Daridorexant matching placebo | Placebo | N/A | — | — | — | N/A |
QUVIVIQ 50 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL USE | 50 | 20 | PRD9668426 |
QUVIVIQ 25 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL USE | 25 | 20 | PRD9668424 |