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

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

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.

Study Overview

• Status: Completed
• Conditions: Insomnia Disorder
• Intervention / Treatment: Other: Placebo; Drug: Daridorexant

• Study Type: Interventional
• Enrollment (Actual): 924
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brugge, Belgium, 8000
    • HOSPITAL AZ SINT-JAN_Neurology department
  • Brussels, Belgium, 1090
    • Hospital Universitair Zieknhuis Brussel, Pneumology and Sleep Laboratory
  • Gent, Belgium, 9000
    • University Hospital Gent, Department of General Internal Medicine and Center of neurophysiological Monitoring
  • Leuven, Belgium, 3000
    • Hospital UZ Leuven_ Pneumology Department
• Bulgaria
  • Sofia, Bulgaria, 1407
    • Acibadem City Clinic Tokuda Hospital Ead
• Canada
  • Etobicoke, Canada, M9C 5N2
    • Queensway Sleep Lab Sleep Clinic (MedSleep)- 5359 Dundas Street West, Suite 202, Etobicoke, ON M9B 1B1
  • Kelowna, Canada, V1Y 3G8
    • The Medical Arts Health Research Group
  • Markham, Canada, L3R 1A3
    • Somni Research Inc.
  • Toronto, Canada, M3H 3W1
    • Somni Research, Calgary
  • Toronto, Canada, M3J 0K2
    • CANADIAN PHASE ONWARD INC. (Toronto)
  • Ontario
    • Toronto, Ontario, Canada, M3J 2C5
      • Canadian Phase Onward Inc.
• Czechia
  • Klecany, Czechia
    • Narodni Ustav Dusevniho Zdravi (National Institute of Mental Health)
  • Ostrava-Poruba, Czechia, 70852
    • Fakultní nemocnice Ostrava, Spánková laboratoř
  • České Budějovice, Czechia, 37087
    • Nemocnice České Budějovice, Centrum pro poruchy spánku a spánkovou medicínu
• Finland
  • Helsinki, Finland, 380
    • Vitalmed Uniklinikka
  • Kuopio, Finland, 70100
    • Oivauni Oy - Kuopio
  • Tampere, Finland
    • Oivauni Oy - Tampere
  • Turku, Finland
    • Unitutkimusyksikkö, Turun Yliopisto
• France
  • Lille, France, 59037
    • CHRU De Lille - Hospital Salengro - Neurophysiologie Clinique
  • Montpellier, France
    • Clinique beau soleil - Department Sleep and Neurology
  • Nîmes, France, 30029
    • CHU NIMES - Unité de Sommeil
• Germany
  • Berlin, Germany, 10117
    • Klinische Forschung Berlin-Mitte GmbH
  • Berlin, Germany, 10117
    • Advanced Sleep Research GmbH
  • Berlin, Germany, 12200
    • Charité - Universitätsmedizin Berlin - Campus Benjamin Franklin Kompetenzzentrum Schlafmedizin
  • Bochum, Germany, 44787
    • Synexus Clinical Research GmbH
  • Dresden, Germany, 1069
    • Klinische Forschung Dresden GmbH
  • Frankfurt, Germany, 60313
    • Synexus Clinical Research GmbH
  • Hannover, Germany, 30159
    • Klinische Forschung Hannover Mitte GmbH
  • Klingenmünster, Germany, 76889
    • Interdisziplinäre Schlafmedizin, Pfalzklinikum
  • Lübeck, Germany, 23538
    • Zentrum für Integrative Psychiatrie (ZiP) Universität zu Lübeck
  • Mannheim, Germany, 68159
    • Central Insitute of Mental Health Sleep laboratory Medical Faculty Mannheim/Heidelberg University
  • Regensburg, Germany, 93053
    • Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie der Universität am Bezirksklinikum Regensburg
  • Schwerin, Germany, 19053
    • SOMNIBENE Institut für Medizinische Forschung und Schlafmedizin Schwerin GmbH
• Hungary
  • Budapest, Hungary, 1134
    • Magyar Honvédség Egészségügyi Központ, Neurológiai Osztály
  • Szeged, Hungary, 6725
    • Somnius Kft. SomnoCenter Szeged
• Korea, Republic of
  • Busan, Korea, Republic of, 49201
    • Dong-A University Hospital
  • Daegu, Korea, Republic of, 41931
    • 4F Neuroimaging analysis laboratory, 56 Dalseong-ro, Jung-gu
  • Daejeon, Korea, Republic of, 35015
    • Chungnam National University Hospital
  • Gwangju, Korea, Republic of, 61469
    • 3F, 2nd Building, Psychiatry Outpatient, Family Counseling Room, 42 Jebong-ro, Donggu
  • Seongnam, Korea, Republic of, 13620
    • 8F Sleep Lab, 1st Building,82, Gumi-ro 173 Beon-gil, Bundang-gu
  • Seoul, Korea, Republic of, 3080
    • 3F Sleep Medicine Center, 101 Daehak-Ro Jongno-Gu
  • Seoul, Korea, Republic of, 3722
    • 1st CRC room, 2F, Jejoong building, 50-1 Yonsei-ro,, Seodaemun-gu
  • Seoul, Korea, Republic of, 5030
    • B2F, Clinical Trial Center, Konkuk University Medical Center 120-1, Neungdong-ro, Gwangjin-gu
  • Seoul, Korea, Republic of, 5278
    • B1F Neurological examination room, 892 Dongnam-ro, Gangdong-gu
  • Suwon, Korea, Republic of, 16247
    • 2F Psychiatry Outpatient, 93, Jungbu-daero, Paldal-gu
• Sweden
  • Göteborg, Sweden, 41390
    • Göteborgs Universitet, Centrum för sömn och vakenhetsstörningar
  • Stockholm, Sweden, 11486
    • SOPHIAHEMMET (Stockholm)
  • Uppsala, Sweden, 75185
    • Sömnutredningsmottagningen, smärtcentrum Akademiska sjukhuset
  • Örebro, Sweden, 70185
    • Universitetssjukhuset Örebro Neurokliniken, Sömnenheten
• United States
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Pulmonary Associates, PA
    • Tucson, Arizona, United States, 85704
      • Noble Clinical Research
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Woodland International Research Group
    • Little Rock, Arkansas, United States, 72205
      • Baptist Health Center for Clinical Research
  • California
    • Cerritos, California, United States, 90703
      • Core Healthcare Group
    • Riverside, California, United States, 92503
      • Artemis Institute for Clinical Research - Riverside
    • San Diego, California, United States, 92103
      • Pacific Research Network
    • San Marcos, California, United States, 92078
      • Artemis Institute for Clinical Research
    • Santa Monica, California, United States, 90404
      • Santa Monica Clinical Trials
    • Upland, California, United States, 91786
      • Empire Clinical Research
  • Colorado
    • Lafayette, Colorado, United States, 80026
      • Innovative Clinical Research
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Clinical Research of South Florida
    • Fleming Island, Florida, United States, 32003
      • Fleming Island Center for Clinical Research
    • Lincoln, Florida, United States, 95648
      • Clinical Trials Research
    • Saint Petersburg, Florida, United States, 33707
      • Clinical Research Group of St. Petersburgh
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Neurotrials Research Incorporated
    • Macon, Georgia, United States, 31210
      • Sleep Practitioners, LLC
  • Hawaii
    • Honolulu, Hawaii, United States, 96817
      • Hawaii Pacific Neurosciences
  • Idaho
    • Nampa, Idaho, United States, 83686
      • Saltzer Clinical Research
  • Kansas
    • Lenexa, Kansas, United States, 66214
      • Rowe Neurology Institute
  • Maryland
    • Glen Burnie, Maryland, United States, 21061
      • Sleep Disorders Center of the Mid-Atlantic
  • Massachusetts
    • Newton, Massachusetts, United States, 02459
      • Neurocare Inc.
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Precise Research Centers
  • New York
    • Garden City, New York, United States, 11530
      • Garden City Asthma and Sleep Center
  • North Carolina
    • Hickory, North Carolina, United States, 28601
      • Research Carolina of Hickory
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates
    • Winston-Salem, North Carolina, United States, 27103
      • Clinical Trials of America - NC, LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • CTI Clinical Research II
    • Dublin, Ohio, United States, 43017
      • Ohio Sleep Medicine Institue
    • Middleburg Heights, Ohio, United States, 44130
      • Cleveland Sleep Research Center
    • Wooster, Ohio, United States, 44691
      • Robert V. Sibilia, MD, Inc.
  • Pennsylvania
    • Paoli, Pennsylvania, United States, 19301
      • Brian Abaluck LLC
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Wesley Neurology Clinic Pc (Multiple Sclerosis)
  • Texas
    • Austin, Texas, United States, 78731
      • FutureSearch Trials of Neurology, LP
    • DeSoto, Texas, United States, 75115
      • InSite Clinical Research
    • Jacksonville, Texas, United States, 32216
      • Jacksonville Center for Clinical Research
    • Tomball, Texas, United States, 77375
      • Dm Clinical Research / Martin Diagnostic Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Matching placebo will be administered as tablets, orally, once daily in the evening.
Experimental: Daridorexant 25 mg	Drug: Daridorexant; Daridorexant will be administered as tablets, orally, once daily in the evening.
Experimental: Daridorexant 10 mg	Drug: Daridorexant; Daridorexant will be administered as tablets, orally, once daily in the evening.

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 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)
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)

Collaborators and Investigators

• Sponsor: Idorsia Pharmaceuticals Ltd.

Publications and helpful links

General Publications

• Hudgens S, Phillips-Beyer A, Newton L, Seboek Kinter D, Benes H. Development and Validation of the Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ). Patient. 2021 Mar;14(2):249-268. doi: 10.1007/s40271-020-00474-z. Epub 2020 Nov 1.
• Mignot E, Mayleben D, Fietze I, Leger D, Zammit G, Bassetti CLA, Pain S, Kinter DS, Roth T; investigators. Safety and efficacy of daridorexant in patients with insomnia disorder: results from two multicentre, randomised, double-blind, placebo-controlled, phase 3 trials. Lancet Neurol. 2022 Feb;21(2):125-139. doi: 10.1016/S1474-4422(21)00436-1. Erratum in: Lancet Neurol. 2022 Jan 20;:. Lancet Neurol. 2022 Jun;21(6):e6.

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2018
• Primary Completion (Actual): April 9, 2020
• Study Completion (Actual): May 14, 2020

Study Registration Dates

• First Submitted: May 17, 2018
• First Submitted That Met QC Criteria: June 20, 2018
• First Posted (Actual): July 2, 2018

Study Record Updates

• Last Update Posted (Actual): March 25, 2022
• Last Update Submitted That Met QC Criteria: March 24, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Sleep Initiation and Maintenance Disorders
• Other Study ID Numbers: ID-078A302

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No