Study to Assess the Efficacy and Safety of ACT-541468 (Daridorexant) in Adult and Elderly Subjects With Insomnia Disorder

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: Drug: Daridorexant 25 mg; Drug: Daridorexant 50 mg; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 930
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia, 5065
    • Respiratory Clinical Trials
  • Auchenflower, Australia, 4066
    • Genesis Sleep Care Queensland
  • East Melbourne, Australia, 3002
    • Melbourne Sleep Disorders Centre
  • Glebe, Australia, 2037
    • The Woolcock Institute Of Medical Research
  • Parkville, Australia, 3052
    • Royal Melbourne Hospital, Department of Respiratory Medicine
  • Southport, Australia, 4215
    • Gold Coast University Hospital, Respiratory Medicine and Sleep Services
  • Westmead, Australia, 2145
    • Westmead Hospital, Department of Respiratory and Sleep Medicine
• Canada
  • Mississauga, Canada, L5B 4M4
    • Tri-Hospital Sleep Laboratory West
  • Quebec, Canada, G1J 2G2
    • CRIUSMQ- CIUSSSCN, CETS (clinique du sommeil)
  • Toronto, Canada, M4P 1P2
    • MedSleep
  • Toronto, Canada, M5G1N8
    • Jodha Tishon Inc.
• Denmark
  • København, Denmark, 1053
    • Scan Sleep Specialists
• Germany
  • Berlin, Germany, 10629
    • emovis GmbH
  • Berlin, Germany, 10115
    • St Hedwig-Krankenhaus, Klinik für Schlaf- und Chronomedizin
  • Berlin, Germany, 12627
    • Synexus Berlin Research Centre
  • Hamburg, Germany, 20253
    • Klinische Forschung Hamburg GmbH
  • Hamburg, Germany, 20251
    • Clinical Trial Center North GmbH & Co. KG
  • Karlsruhe, Germany, 76137
    • Klinische Forschung Karlsruhe GmbH
  • Kassel, Germany, 34131
    • Studienzentrum Wilhelmshöhe GmbH
  • Leipzig, Germany, 4103
    • Synexus Leipzig Research Centre
  • München, Germany, 81675
    • Klinikum Rechts der lsar TU München Dept. of Psychiatry and Psychotherapy
  • Schwerin, Germany, 19055
    • Kinische Forschung Schwerin GmbH
  • Warendorf, Germany, 48231
    • ZMS Zentrum für medizinische Studien GmbH
• Italy
  • Milano, Italy, 20127
    • Ospedale San Raffaele - Centro per i Disturbi del Sonno San Raffaele - Ville-Turro - Pallazzina E
  • Pavia, Italy, 27100
    • IRCCS FONDAZIONE Istituto Neurologico Nazionale "Casimiro Mondino" - Centro di Ricerca Interdipartimentale per la SSclerosi Multipla (CRISM) -
  • Pisa, Italy, 56126
    • Azienda Ospedaliero Universitaria Pisana - Ospedale S. Chiara - Centro di Medicina del Sonno - Clinica Neuroligica - Dipartimento de Neuroscienze
  • Torino, Italy, 10146
    • AOU Citta della Salute e della Scienza - Molinette - SSD Medicina del Sonno
• Poland
  • Gdańsk, Poland, 80-546
    • PI-House - Centrum Badań Klinicznych
  • Warsaw, Poland, 02-957
    • Ośrodek Medycyny Study Nurseu Instytutu Psychiatrii i Neurologii (Sleep Disorders Center)
  • Wroclaw, Poland, 50220
    • EMC Instytut Medyczny SA, Przychodnia przy Łowieckiej
• Serbia
  • Belgrade, Serbia, 11000
    • General Hospital Bel Medic, Center for Sleep disorders
  • Novi Beograd, Serbia, 11070
    • Medigroup - Health Center Dr Ristic (MediGroup Dom zdravlja "Dr Ristic") - Neurology Department
• Spain
  • Barcelona, Spain, 8017
    • Centro Médico Teknon - Medicina del Sueño
  • Barcelona, Spain, 8025
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain, 8035
    • Hospital Universitari Vall d'Hebron - Neurophisiology Deparment - Sleep Unit
  • Castelló de la Plana, Spain, 12004
    • Hospital General de Castellón
  • Madrid, Spain, 28036
    • Instituto de Investigaciones del Sueño
  • Madrid, Spain, 28040
    • San Carlos University Hospital - Servicio de Neurofisiología Clínica
  • Vitoria-Gasteiz, Spain, 1004
    • Hospital Universitario Araba - Unidad Funcional de Trastornos del Sueño
  • Zaragoza, Spain, 50015
    • Hospital MAZ - Neurophisiology and Sleep Department
• Switzerland
  • Bad Zurzach, Switzerland, 5330
    • KSM Bad Zurzach, Klinik für Schlafmedizin
  • Basel, Switzerland, 4002
    • Universitäre Psychiatrische Kliniken Basel (UPK)
  • Bern, Switzerland, 3010
    • Universitätsklinik für Neurologie, Inselspital Bern, Schlaf-Wach-Epilepsie-Zentrum
  • Wald, Switzerland, 8636
    • Zentrum für Schlafmedizin Zürcher Oberland, Zürcher RehaZentrum Wald
  • Wetzikon, Switzerland, 8620
    • Zentrum für Schlafmedizin GZO AG Spital Wetzikon
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Pinnacle Research Group, LLC
    • Birmingham, Alabama, United States, 35243
      • Pulmonary Associates of the Southeast/WCR
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Preferred Research Partners, Inc
    • Rogers, Arkansas, United States, 72758
      • Woodland Research Northwest
  • California
    • Huntington Beach, California, United States, 92647
      • Marvel Clinical Research
    • Long Beach, California, United States, 90806
      • Long Beach Clinical Trials
    • San Diego, California, United States, 92103
      • Artemis Institute for Clinical Research
  • Florida
    • Brandon, Florida, United States, 33511
      • PAB Clinical Research
    • Clearwater, Florida, United States, 33765
      • St. Francis Sleep Allergy and Lung Institute
    • Hialeah, Florida, United States, 33012
      • Innovative Clinical Research, Inc.
    • Hollywood, Florida, United States, 33024
      • Research Centers of America
    • Lake Worth, Florida, United States, 33467
      • Canvas Clinical Research, LLC
    • Miami, Florida, United States, 33126
      • BioMed Research Institute
    • Winter Park, Florida, United States, 32789
      • Clinical Site Partners, LLC
  • Indiana
    • Michigan City, Indiana, United States, 46360
      • LaPorte County Institute for Clinical Research
  • Kentucky
    • Louisville, Kentucky, United States, 40218
      • Kentucky Research Group
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • Helene Emsellem, MD
  • Massachusetts
    • North Dartmouth, Massachusetts, United States, 02747
      • Infinity Medical Research, Inc.
  • Nebraska
    • La Vista, Nebraska, United States, 68128
      • Barrett Clinic
  • Nevada
    • Las Vegas, Nevada, United States, 89104
      • Clinical Research Center of Nevada
  • New York
    • New York, New York, United States, 10019
      • Clinilabs NYC
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • Research Carolina of Huntersville
    • New Bern, North Carolina, United States, 28562
      • Coastal Carolina Healthcare
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • CTI Clinical Research Center
  • Oregon
    • Salem, Oregon, United States, 97301
      • Oregon Center for Clinical Investigations,Inc
  • Rhode Island
    • Lincoln, Rhode Island, United States, 02865
      • BTC of Lincoln
    • Warwick, Rhode Island, United States, 02886
      • Omega Medical Research
  • South Carolina
    • Columbia, South Carolina, United States, 29201
      • Bogan Sleep Consulting, LLC
    • Mount Pleasant, South Carolina, United States, 29464
      • Coastal Carolina Research Center
  • Tennessee
    • Johnson City, Tennessee, United States, 37604
      • Tri-State Mountain Neurology
  • Texas
    • Baytown, Texas, United States, 77521
      • Inquest Clinical Research
    • San Antonio, Texas, United States, 78229
      • Sleep Therapy & Research Center
  • Utah
    • Orem, Utah, United States, 84058
      • Aspen Clinical Research
  • Virginia
    • Richmond, Virginia, United States, 23225
      • Pulmonary Associates of Richmond
    • Vienna, Virginia, United States, 22182
      • Sleep Disorders Centers of the Mid-Atlantic
  • Washington
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center

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;
• 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 25 mg; Daridorexant will be administered as tablets, orally, once daily in the evening.
Experimental: Daridorexant 50 mg	Drug: Daridorexant 50 mg; 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 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)

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.
• Fietze I, Bassetti CLA, Mayleben DW, Pain S, Seboek Kinter D, McCall WV. Efficacy and Safety of Daridorexant in Older and Younger Adults with Insomnia Disorder: A Secondary Analysis of a Randomised Placebo-Controlled Trial. Drugs Aging. 2022 Oct;39(10):795-810. doi: 10.1007/s40266-022-00977-4. Epub 2022 Sep 13.

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2018
• Primary Completion (Actual): January 25, 2020
• Study Completion (Actual): February 25, 2020

Study Registration Dates

• First Submitted: May 22, 2018
• First Submitted That Met QC Criteria: May 22, 2018
• First Posted (Actual): June 4, 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-078A301

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