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

Study Overview
=================
Brief Summary
-----------------
This study evaluates the dose response of ACT-541468 on the change of WASO from baseline to Days 1 and 2, assessed by PSG.

Detailed Description
-----------------
This study consists of the following phases: screening phase; double-blind treatment phase; safety follow-up phase. Safety is monitored throughout the study.

Official Title
-----------------
Multi-center, Double-blind, Randomized, Placebo-controlled, Active-reference, Parallel-group, Polysomnography Dose-response Study to Assess the Efficacy and Safety of ACT-541468 in Adult Subjects With Insomnia Disorder

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

Intervention / Treatment
-----------------
* Drug: ACT-541468 5 mg
* Drug: ACT-541468 10 mg
* Drug: ACT-541468 25 mg
* Drug: Zolpidem
* Drug: Placebo 1
* Drug: Placebo 2


Participation Criteria
=================
Eligibility Criteria
-----------------
Principal inclusion Criteria: Signed informed consent prior to any study-mandated procedure. Male or female aged 18-64 years (inclusive). Women of childbearing potential must have negative pregnancy tests and use reliable methods of contraception up to 30 days after EOT. Body mass index (BMI): 18.5 ≤ BMI (kg/m2) < 32.0. Insomnia disorder according to DSM-5 criteria. Insufficient sleep quantity as collected subjectively in the sleep diary and validated objectively by polysomnography. Insomnia Severity Index score ≥ 15. Principal 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 > or= 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 direct 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
-----------------
Minimum Age: 18 Years
Maximum Age: 64 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: ACT-541468 5 mg<br>Each subject receives one 5-mg ACT-541468 capusle (+ one placebo capsule), once daily in the evening for 4 weeks | Drug: ACT-541468 5 mg<br>* Capsule for oral administration containing ACT-541468 at a strength of 5 mg<br>Drug: Placebo 1<br>* Placebo capsules matching ACT-541468 capsules<br>|
| Experimental: ACT-541468 10 mg<br>Each subject receives one 10-mg ACT-541468 capusle (+ one placebo capsule), once daily in the evening for 4 weeks | Drug: ACT-541468 10 mg<br>* Capsule for oral administration containing ACT-541468 at a strength of 10 mg<br>Drug: Placebo 1<br>* Placebo capsules matching ACT-541468 capsules<br>|
| Experimental: ACT-541468 25 mg<br>Each subject receives one 25-mg ACT-541468 capsule (+ one placebo capsule), once daily in the evening) for 4 weeks | Drug: ACT-541468 25 mg<br>* Capsule for oral administration containing ACT-541468 at a strength of 25 mg<br>Drug: Placebo 1<br>* Placebo capsules matching ACT-541468 capsules<br>|
| Experimental: ACT-541468 50 mg<br>Each subject receives two 25-mg ACT-541468 capsules, once daily in the evening for 4 weeks | Drug: ACT-541468 25 mg<br>* Capsule for oral administration containing ACT-541468 at a strength of 25 mg<br>|
| Active Comparator: Zolpidem<br>Each subject receives one 10-mg zolpidem capsule (+ one placebo capusle), once daily in the evening for 4 weeks | Drug: Zolpidem<br>* Over-encapsulated zolpidem tablet at a strength of 10 mg<br>Drug: Placebo 2<br>* Placebo capsules matching over-encapsulated zolpidem<br>|
| Placebo Comparator: Placebo<br>Each subject receives two placebo capsules, once daily in the evening for 4 weeks | Drug: Placebo 1<br>* Placebo capsules matching ACT-541468 capsules<br>|

What is the study measuring?
-----------------
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 and Days 1&2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 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 and Days 1&2 | 
| Change in Subjective Latency to Sleep Onset (sLSO) From Baseline to Week 4 | sLSO is the self-reported time to fall asleep, as reported in the sleep diary | Baseline and Week 4 | 
| Change in Subjective Wake After Sleep Onset (sWASO) From Baseline to Week 4 | sWASO is the self-reported time spent awake after sleep onset as reported in the sleep diary. | Baseline and Week 4 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Insomnia, Polysomnography