Efficacy and Safety of ACT-541468 in Elderly Subjects With Insomnia Disorder

Study Overview
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Brief Summary
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This study evaluates the dose response of ACT-541468 on the change of wake after sleep onset (WASO) assessed by polysomnography (PSG) on the first 2 days of each treatment period.

Detailed Description
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The study consists of 3 phases: a screening phase, a double-blind treatment phase consisting of 5 periods, and a safety follow-up phase. Safety is monitored throughout the study.

Official Title
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Multi-center, Double-blind, Randomized, Placebo-controlled, 5-period, 5-treatment Crossover, Polysomnography Dose-response Study to Assess the Efficacy and Safety of ACT-541468 in Elderly Subjects With Insomnia Disorder

Conditions
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Insomnia Disorder

Intervention / Treatment
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* Drug: ACT-541468
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent prior to any study-mandated procedure. Male or female aged ≥ 65 years. Body mass index (BMI): 18.5 ≤ BMI (kg/m2 ) < 32.0 Insomnia disorder according to DSM-5 criteria. Self-reported history of insufficient sleep quantity. Insufficient sleep quantity as collected subjectively in the sleep diary and validated objectively by polysomnography. Insomnia Severity Index score ≥ 15. Exclusion Criteria: Any current history of sleep disorder other than insomnia, or any lifetime history of related breathing disorder, periodic limb movement disorder, restless legs syndrome, circadian rhythm disorder, rapid eye movement (REM) behavior disorder, or narcolepsy. Self-reported usual daytime napping ≥ 1 hour per day, and ≥ 3 days per week. Caffeine consumption ≥ 600 mg per day. Shift work within 2 weeks prior to the screening visit, or planned shift work during study. Travel ≥ 3 time zones within 1 week prior to the screening visit, or planned travel ≥ 3 time zones during study. Hematology or biochemistry test results deviating from the normal range to a clinically relevant extent as per judgment of the Investigator. AST and/or ALT > 2 × ULN and/or bilirubin > 1.5 × ULN (except known history of Gilbert's syndrome); Severe renal impairment (known or defined as estimated creatinine clearance < 30 mL/min); 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
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Minimum Age: 65 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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence 1<br>Each subject participates in 5 treatment periods. On the evening of the first 2 days of each period they receive one dose (D) of ACT-541468 or placebo orally in the following order: D4, D2, D3, D1 and P, with D4 = the highest dose (50 mg) and D1 the lowest dose (5 mg). Each treatment period is separated from the next one by a 5- to 12-day washout. | Drug: ACT-541468<br>* Capsules for oral administration containing ACT-541468 at a strength of 5 mg, 10 mg or 25 mg<br>Drug: Placebo<br>* Capsules for oral administration matching the ACT-541468 capsules<br>|
| Experimental: Sequence 2<br>Each subject participates in 5 treatment periods. On the evening of the first 2 days of each period they receive one dose (D) of ACT-541468 or placebo orally in the following order: D2, P, D4, D3 and D1, with D4 = the highest dose (50 mg) and D1 the lowest dose (5 mg). Each treatment period is separated from the next one by a 5- to 12-day washout. | Drug: ACT-541468<br>* Capsules for oral administration containing ACT-541468 at a strength of 5 mg, 10 mg or 25 mg<br>Drug: Placebo<br>* Capsules for oral administration matching the ACT-541468 capsules<br>|
| Experimental: Sequence 3<br>Each subject participates in 5 treatment periods. On the evening of the first 2 days of each period they receive one dose (D) of ACT-541468 or placebo orally in the following order: D3, D1, D2, P and D4, with D4 = the highest dose (50 mg) and D1 the lowest dose (5 mg). Each treatment period is separated from the next one by a 5- to 12-day washout. | Drug: ACT-541468<br>* Capsules for oral administration containing ACT-541468 at a strength of 5 mg, 10 mg or 25 mg<br>Drug: Placebo<br>* Capsules for oral administration matching the ACT-541468 capsules<br>|
| Experimental: Sequence 4<br>Each subject participates in 5 treatment periods. On the evening of the first 2 days of each period they receive one dose (D) of ACT-541468 or placebo orally in the following order: P, D4, D1, D2, D3, with D4 = the highest dose (50 mg) and D1 the lowest dose (5 mg). Each treatment period is separated from the next one by a 5- to 12-day washout. | Drug: ACT-541468<br>* Capsules for oral administration containing ACT-541468 at a strength of 5 mg, 10 mg or 25 mg<br>Drug: Placebo<br>* Capsules for oral administration matching the ACT-541468 capsules<br>|
| Experimental: Sequence 5<br>Each subject participates in 5 treatment periods. On the evening of the first 2 days of each period they receive one dose (D) of ACT-541468 or placebo orally in the following order: D1, D3, P, D4 and D2 with D4 = the highest dose (50 mg) and D1 the lowest dose (5 mg). Each treatment period is separated from the next one by a 5- to 12-day washout. | Drug: ACT-541468<br>* Capsules for oral administration containing ACT-541468 at a strength of 5 mg, 10 mg or 25 mg<br>Drug: Placebo<br>* Capsules for oral administration matching the ACT-541468 capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Wake After Sleep Onset (WASO) From Baseline to Days 1 and 2 | WASO is the time in minutes spent awake after onset of persistent sleep until lights on as determined by polysomnography (PSG) | Baseline to Day 1 and Day 2 of each treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean Latency to Persistent Sleep (LPS) From Baseline to Days 1 and 2 | LPS is the duration of time in minutes from lights off to persistent sleep onset as determined by PSG | Baseline to Day 1 and Day 2 of each treatment period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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insomnia, elderly, Polysomnography