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

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

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

Study Overview

• Status: Completed
• Conditions: Insomnia Disorder
• Intervention / Treatment: Drug: ACT-541468 5 mg; Drug: Placebo 1; Drug: ACT-541468 10 mg; Drug: ACT-541468 25 mg; Drug: Zolpidem; Drug: Placebo 2

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.

• Study Type: Interventional
• Enrollment (Actual): 360
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10115
    • Investigator site
  • Berlin, Germany, 10117
    • Investigator site
  • Berlin, Germany, 12203
    • Investigator site
  • Dresden, Germany, 01069
    • Investigator site
  • Hamburg, Germany, 20253
    • Investigator site
  • Hamburg, Germany, 20251
    • Investigator site
  • Hannover, Germany, 30159
    • Investigator site
  • Schwerin, Germany, 19053
    • Investigator site
  • Schwerin, Germany, 19055
    • Investigator site
• Hungary
  • Budapest, Hungary, 1134
    • Investigator site
  • Szeged, Hungary, 6725
    • Investigator site
  • Törökbálint, Hungary, 2045
    • Investigator site
• Israel
  • Beer Sheva, Israel, 84101
    • Investigator site
  • Haifa, Israel, 31096
    • Investigator site
• Spain
  • Barcelona, Spain, 08035
    • Investigator site
  • Barcelona, Spain, 08017
    • Investigator site
  • Madrid, Spain, 28036
    • Investigator site
  • Zaragoza, Spain, 50015
    • Investigator site
• Sweden
  • Göteborg, Sweden, 413 90
    • Investigator site
  • Örebro, Sweden, 701 85
    • Investigator site
• United States
  • California
    • Santa Monica, California, United States, 90404
      • Investigator site
    • Upland, California, United States, 91786
      • Investigator site
  • Florida
    • Brandon, Florida, United States, 33511
      • Investigator site
    • Clearwater, Florida, United States, 33765
      • Investigator site
    • Coral Gables, Florida, United States, 33134
      • Investigator site
    • DeLand, Florida, United States, 32720
      • Investigator site
    • Hollywood, Florida, United States, 33024
      • Investigator site
    • Miami, Florida, United States, 33143
      • Investigator site
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Investigator site
  • Illinois
    • Chicago, Illinois, United States, 60634
      • Investigator site
  • Indiana
    • Indianapolis, Indiana, United States, 46250
      • Investigator site
  • Michigan
    • Novi, Michigan, United States, 48377
      • Investigator site
  • Nevada
    • Las Vegas, Nevada, United States, 89104
      • Investigator site
  • New York
    • New York, New York, United States, 10019
      • Investigator site
  • Ohio
    • Cincinnati, Ohio, United States, 45255
      • Investigator site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ACT-541468 5 mg; 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; Capsule for oral administration containing ACT-541468 at a strength of 5 mg; Drug: Placebo 1; Placebo capsules matching ACT-541468 capsules
Experimental: ACT-541468 10 mg; Each subject receives one 10-mg ACT-541468 capusle (+ one placebo capsule), once daily in the evening for 4 weeks	Drug: Placebo 1; Placebo capsules matching ACT-541468 capsules; Drug: ACT-541468 10 mg; Capsule for oral administration containing ACT-541468 at a strength of 10 mg
Experimental: ACT-541468 25 mg; Each subject receives one 25-mg ACT-541468 capsule (+ one placebo capsule), once daily in the evening) for 4 weeks	Drug: Placebo 1; Placebo capsules matching ACT-541468 capsules; Drug: ACT-541468 25 mg; Capsule for oral administration containing ACT-541468 at a strength of 25 mg
Experimental: ACT-541468 50 mg; Each subject receives two 25-mg ACT-541468 capsules, once daily in the evening for 4 weeks	Drug: ACT-541468 25 mg; Capsule for oral administration containing ACT-541468 at a strength of 25 mg
Active Comparator: Zolpidem; Each subject receives one 10-mg zolpidem capsule (+ one placebo capusle), once daily in the evening for 4 weeks	Drug: Zolpidem; Over-encapsulated zolpidem tablet at a strength of 10 mg; Drug: Placebo 2; Placebo capsules matching over-encapsulated zolpidem
Placebo Comparator: Placebo; Each subject receives two placebo capsules, once daily in the evening for 4 weeks	Drug: Placebo 1; Placebo capsules matching ACT-541468 capsules

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

Collaborators and Investigators

• Sponsor: Idorsia Pharmaceuticals Ltd.

Publications and helpful links

General Publications

• Dauvilliers Y, Zammit G, Fietze I, Mayleben D, Seboek Kinter D, Pain S, Hedner J. Daridorexant, a New Dual Orexin Receptor Antagonist to Treat Insomnia Disorder. Ann Neurol. 2020 Mar;87(3):347-356. doi: 10.1002/ana.25680. Epub 2020 Feb 5. Erratum In: Ann Neurol. 2020 Sep;88(3):647-651.

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2016
• Primary Completion (Actual): April 12, 2017
• Study Completion (Actual): June 20, 2017

Study Registration Dates

• First Submitted: July 18, 2016
• First Submitted That Met QC Criteria: July 18, 2016
• First Posted (Estimate): July 20, 2016

Study Record Updates

• Last Update Posted (Actual): April 13, 2020
• Last Update Submitted That Met QC Criteria: April 1, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Polysomnography; Insomnia
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Sleep Initiation and Maintenance Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Hypnotics and Sedatives; GABA Agents; Sleep Aids, Pharmaceutical; GABA-A Receptor Agonists; GABA Agonists; Zolpidem
• Other Study ID Numbers: AC-078A201