Study to Assess the Efficacy and Safety of ACT-541468 (Daridorexant) in Adult and Elderly Subjects Suffering From Difficulties to Sleep

Study Overview
=================
Brief Summary
-----------------
The main purpose of this study is to assess efficacy and safety of ACT-541468 (daridorexant) in adult and elderly subjects with insomnia disorder. Efficacy will be evaluated on objective and subjective sleep parameters.

Official Title
-----------------
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

Conditions
-----------------
Insomnia Disorder

Intervention / Treatment
-----------------
* Drug: Daridorexant
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed informed consent prior to any study-mandated procedure; Male or female aged ≥ 18 years; Insomnia disorder according to DSM-5 criteria; Insomnia Severity Index score ≥ 15; Insufficient sleep quantity as collected subjectively in the sleep diary and validated objectively by polysomnography; Women of childbearing potential must have a negative and urine pregnancy test and use the contraception scheme up to at least 30 days after last study treatment intake. Exclusion Criteria: Body mass index below 18.5 or above 40.0 kg/m2; Any lifetime history of of related breathing disorder, periodic limb movement disorder, restless legs syndrome, circadian rhythm disorder, rapid eye movement (REM) behavior disorder, narcolepsy, or apnea/hypopnea; Cognitive behavioral therapy (CBT) only allowed if, the treatment started at least 1 month prior to Visit 3 and the subject agrees to continue this CBT throughout the study; Self-reported usual daytime napping ≥ 1 hour per day and ≥ 3 days per week; Acute or unstable psychiatric conditions diagnosed by the Mini International Neuropsychiatric Interview; Mini Mental State Examination (MMSE) score < 25 in subjects ≥ 50 years; For female subjects: pregnant, lactating or planning to become pregnant during projected duration of the study; History or clinical evidence of any disease or medical condition or treatment, which may put the subject at risk of participation in the study or may interfere with the study assessments. Any circumstances or conditions, which, in the opinion of the investigator, may affect the subject's full participation in the study or compliance with the protocol.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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<br>* Daridorexant will be administered as tablets, orally, once daily in the evening.<br>|
| Experimental: Daridorexant 25 mg<br> | Drug: Daridorexant<br>* Daridorexant will be administered as tablets, orally, once daily in the evening.<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Matching placebo will be administered as tablets, orally, once daily in the evening.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Month 1 in Wake After Sleep Onset (WASO) (Sleep Maintenance) | Wake After Sleep Onset is the time spent awake after onset of persistent sleep until lights on, as determined by polysomnography. | From baseline to Month 1 (i.e. for up to 1 month) | 
| Change From Baseline to Month 3 in Wake After Sleep Onset (WASO) | Wake After Sleep Onset is the time spent awake after onset of persistent sleep until lights on, as determined by polysomnography. | From baseline to Month 3 (i.e. for up to 3 months) | 
| Change From Baseline to Month 1 in Latency to Persistent Sleep (LPS) (Sleep Onset) | Latency to Persistent Sleep is the time from start of recording to the beginning of the first continuous 20 epochs (i.e., 10 minutes) scored as non-awake, i.e., epochs scored as either sleep stage 1 (S1), sleep stage 2 (S2), sleep stage 3 (slow wave sleep) or REM, as determined by polysomnography. | From baseline to Month 1 (i.e. for up to 1 month) | 
| Change From Baseline to Month 3 in Latency to Persistent Sleep (LPS) | Latency to Persistent Sleep is the time from start of recording to the beginning of the first continuous 20 epochs (i.e., 10 minutes) scored as non-awake, i.e., epochs scored as either sleep stage 1 (S1), sleep stage 2 (S2), sleep stage 3 (slow wave sleep) or REM, as determined by polysomnography. | From baseline to Month 3 (i.e. for up to 3 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Month 1 in the Subjective Total Sleep Time (sTST) | Subjective Total Sleep Time is the total sleep time reported by the participant in the sleep diary questionnaire. A positive change from baseline indicates an increase in the subjective Total Sleep Time. A negative change from baseline indicates a decrease in subjective Total Sleep Time. | From baseline to Month 1 (i.e. for up to 1 month) | 
| Change From Baseline to Month 3 in the Subjective Total Sleep Time (sTST) | Subjective Total Sleep Time is the total sleep time reported by the participant in the sleep diary questionnaire. A positive change from baseline indicates an increase in the subjective Total Sleep Time. A negative change from baseline indicates a decrease in subjective Total Sleep Time. | From baseline to Month 3 (i.e. for up to 3 months) | 
| Change From Baseline to Month 1 in Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ) Sleepiness Domain Score | The Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ) is a validated patient reported outcome instrument comprising 14 items (each using a numeric rating scale from 0 to 10) grouped into three domains (i.e., sleepiness, mood, and alert/cognition) reflecting daytime impairment of insomnia. The IDSIQ sleepiness domain has 4 items, and the domain score ranges from 0 to a maximum of 40, where a higher score indicates a greater burden. A negative change from baseline indicates an improvement and a positive change from baseline indicates a worsening. | From baseline to Month 1 (i.e. for up to 1 month) | 
| Change From Baseline to Month 3 in IDSIQ Sleepiness Domain Score | The Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ) is a validated patient reported outcome instrument comprising 14 items (each using a numeric rating scale from 0 to 10) grouped into three domains (i.e., sleepiness, mood, and alert/cognition) reflecting daytime impairment of insomnia. The IDSIQ sleepiness domain has 4 items, and the domain score ranges from 0 to a maximum of 40, where a higher score indicates a greater burden. A negative change from baseline indicates an improvement and a positive change from baseline indicates a worsening. | From baseline to Month 3 (i.e. for up to 3 months) |