Study of the Efficacy and Safety of Lemborexant in Subjects 55 Years and Older With Insomnia Disorder (SUNRISE 1) (SUNRISE 1)

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Active Comparator, Parallel-Group Study of the Efficacy and Safety of Lemborexant in Subjects 55 Years and Older With Insomnia Disorder (SUNRISE 1)

This study will be conducted to demonstrate, using polysomnography, that lemborexant 10 milligrams (mg) and 5 mg is superior to placebo on objective sleep onset as assessed by latency to persistent to sleep (LPS) after the last 2 nights of 1 month of treatment in participants 55 years and older with insomnia disorder.

Study Overview

• Status: Completed
• Conditions: Insomnia
• Intervention / Treatment: Drug: Lemborexant; Drug: Lemborexant; Drug: Zolpidem-matched placebo; Drug: Lemborexant-matched placebo; Drug: Zolpidem tartrate

Detailed Description

The study is a multicenter, randomized, double-blind, placebo-controlled, active comparator, parallel-group study of 2 dose levels of lemborexant for 30 nights in approximately 950 participants, 55 years or older with insomnia disorder. Participants will be males 65 years or older or females 55 years or older. Approximately 60% of the participants will be age 65 years or older. The study will have 2 phases: The Prerandomization Phase and the Randomization Phase. Including both phases, the study will last for a minimum of 65 and a maximum of 81 days per participant.

• Study Type: Interventional
• Enrollment (Actual): 1006
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • Sleep and Fatigue Institute
  • British Columbia
    • Kelowna, British Columbia, Canada
      • Medical Arts Health Research Group
  • Ontario
    • Markham, Ontario, Canada, L3R 1A3
    • Markham, Ontario, Canada
      • Somni Research Inc.
    • Mississauga, Ontario, Canada
      • Tri Hospital Sleep West
    • Scarborough, Ontario, Canada
      • Sleep Wake Disorders Clinic
    • Toronto, Ontario, Canada, M4P 1P2
    • Toronto, Ontario, Canada
      • Toronto Sleep Institute
• France
  • Bordeaux, France
    • Centre Hospitalier Universitaire de Bordeaux, Hopital Pellegrin
  • Clermont-ferrand, France
    • Hôpital Gabriel Montpied
  • Dijon Cedex, France
    • CHU Dijon Bourgogne
  • Paris, France
    • Hôtel Dieu de Paris Hospital
  • Strasbourg, France
    • Hôpital CIVIL
• Germany
  • Berlin, Germany
    • emovis GmbH
  • Berlin, Germany
    • Advanced Sleep Research GmbH
  • Kassel, Germany
    • Studienzentrum Wilhelmshöhe
  • München, Germany
    • Klinikum rechts der Isar der Technischen Universitat Munchen
  • Münster, Germany
    • Universitätsklinikum Münster
  • Schwerin, Germany
    • Somni Bene Institut fur Medizinische Forschung und Schlafmedizin Schwerin GmbH
  • Baden-Württemberg
    • Mannheim, Baden-Württemberg, Germany
      • Zentralinstitut für seelische Gesundheit
  • Schleswig-Holstein
    • Lübeck, Schleswig-Holstein, Germany
      • Universitätsklinikum Schleswig-Holstein
• Italy
  • Parma, Italy
    • Azienda Ospedaliero Universitaria di Parma
  • Pavia, Italy
    • ASST di Pavia - Fondazione Istituto Neurologico Mondino IRCCS
  • Pisa, Italy
    • Azienda Ospedaliero Universitaria Pisana
  • Roma, Italy
    • Fondazione PTV Policlinico Tor Vergata
  • Torino, Italy
    • Azienda Ospedaliera Citta Della Salute E Della Scienza Di Torino
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy
      • Ospedale Bellaria
  • Lombardia
    • Milan, Lombardia, Italy
      • Ospedale San Raffaele S.r.l. - PPDS
• Spain
  • Badalona, Spain
    • Hospital Clinic De Barcelona
  • Barcelona, Spain
    • Hospital de La Santa Creu i Sant Pau
  • Barcelona, Spain, 08025
  • Barcelona, Spain
    • Clinica del Son Estivill
  • La Coruña, Spain
    • Hospital San Rafael
  • Madrid, Spain
    • Hospital Universitario La Paz
  • Madrid, Spain
    • Hospital Universitario Fundación Jiménez Díaz
  • Madrid, Spain
    • Instituto de Investigaciones del Sueño
  • Vitória, Spain
    • Hospital Universitario Araba - Txagorritxu
  • Navarra
    • Pamplona, Navarra, Spain
      • Clinica Universidad de Navarra
• United Kingdom
  • London, United Kingdom
    • Guys Hospital
  • Stoke on Trent, United Kingdom
    • Royal Stoke University Hospital
  • Cambridge Shire
    • Cambridge, Cambridge Shire, United Kingdom
      • Papworth Hospital
  • Surrey
    • Guildford, Surrey, United Kingdom
      • University of Surrey
• United States
  • Alabama
    • Jasper, Alabama, United States, 35501
      • Jasper Summit Research LLC
  • Arizona
    • Glendale, Arizona, United States, 85306
      • PACT
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Preferred Research Partners
  • California
    • Carlsbad, California, United States, 92011
    • Fountain Valley, California, United States, 92708
      • Southern California Research
    • Oceanside, California, United States, 92054
      • Pacific Sleep Medicine Services
    • Oceanside, California, United States, 92056
      • Research Center of Southern California
    • Orange, California, United States, 92868
      • SDS Clinical Trials, Inc.
    • Orange, California, United States, 92868
      • Orange County Neuropsychiatric Research Center, LLC
    • San Diego, California, United States, 92103
      • Pacific Research Network Inc
    • San Diego, California, United States, 92103
      • Artemis Institute for Clinical Research LLC
    • 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
  • Florida
    • Brandon, Florida, United States, 33511
      • PAB Clinical Research
    • Clearwater, Florida, United States, 33765
      • Saint Francis Sleep Allergy and Lung Institute
    • Fleming Island, Florida, United States, 32003
      • Fleming Island Center for Clinical Research
    • Gainesville, Florida, United States, 32607
      • Sarkis Clinical Trials
    • Hallandale Beach, Florida, United States, 33009
      • MD Clinical
    • Hollywood, Florida, United States, 33024
      • QPS MRA
    • Miami, Florida, United States, 33143
      • Quest Pharmaceutical Services-Miami Research Associates, LLC (QPS MRA)
    • Oakland Park, Florida, United States
      • Research Centers of America
    • Orlando, Florida, United States, 32806
      • Compass Research LLC
    • Panama City, Florida, United States, 32405
      • NeuroMedical Research Institute
    • Saint Petersburg, Florida, United States, 33707
      • Clinical Research Group of St Petersburg Inc
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • NeuroTrials Research Inc.
    • Stockbridge, Georgia, United States, 30281
      • SleepCare Research Institute Inc
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60634
      • Chicago Research Center Inc
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • Helene A Emsellem MD PC
    • Glen Burnie, Maryland, United States, 21061
      • Sleep Disorders Center of the Mid-Atlantic
  • Massachusetts
    • Newton, Massachusetts, United States, 02459
      • Neurocare Inc
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Novi, Michigan, United States, 48377
      • Henry Ford Hospital
    • Sterling Heights, Michigan, United States, 48314
      • Clinical Neurophysiology Services
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • St. Louis Clinical Trials
    • Saint Louis, Missouri, United States, 63143
      • Clayton Sleep Institute
  • Nevada
    • Las Vegas, Nevada, United States, 89104
      • Clinical Research Center Of Nevada
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Hassman Research Institute
    • Eatontown, New Jersey, United States, 07724
      • Clinilabs, Inc.
  • New York
    • Garden City, New York, United States, 11530
      • Winthrop University Hospital
    • New York, New York, United States, 10019
      • Clinical Research Unit
    • Rochester, New York, United States, 14642
      • University of Rochester
    • Staten Island, New York, United States, 10312
      • Richmond Behavioral Associates
    • West Seneca, New York, United States, 14224
      • Sleep Medicine Centers of Western New York
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates, LLC
    • Wilmington, North Carolina, United States, 28401
      • Wilmington Health Associates
  • Ohio
    • Cincinnati, Ohio, United States, 45212
    • Cincinnati, Ohio, United States, 45245
      • Intrepid Research
    • Cincinnati, Ohio, United States, 45255
      • CTI Clinical Research Center
    • Dublin, Ohio, United States, 43017
      • Ohio Sleep Medicine Institute
    • Middleburg Heights, Ohio, United States, 44130
      • Cleveland Sleep Research Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Health Science Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104-3309
      • University of Pennsylvania
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina - PPDS
    • Columbia, South Carolina, United States, 29201
      • SleepMed of South Carolina
  • Texas
    • Houston, Texas, United States, 77099
      • Pioneer Research Solutions
  • Virginia
    • Vienna, Virginia, United States, 22182
      • Sleep Disorders Center of the Mid-Atlantic
  • Washington
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center
    • Seattle, Washington, United States, 98101

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 53 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

1. Male age 65 years or older or female age 55 years or older at the time of informed consent

2. Meets the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for Insomnia Disorder, as follows:

   • Complains of dissatisfaction with nighttime sleep, in the form of difficulty staying asleep and/or awakening earlier in the morning than desired despite adequate opportunity for sleep (Note that if the complaint is limited to difficulty initiating sleep, the participant is not eligible)
   • Frequency of complaint ≥ 3 times per week
   • Duration of complaint ≥ 3 months
   • Associated with complaint of daytime impairment
3. History of subjective wake after sleep onset (sWASO) typically ≥ 60 minutes on at least 3 nights per week in the previous 4 weeks
4. Reports regular time spent in bed, either sleeping or trying to sleep, between 7 and 9 hours
5. Reports habitual bedtime, defined as the time the participant attempts to sleep, between 21:00 and 24:00 and habitual waketime between 05:00 and 09:00
6. Insomnia Severity Index (ISI) score ≥ 13
7. Confirmation of current insomnia symptoms as determined from responses on the Sleep Diary before the second screening visit
8. Confirmation of regular bedtime and waketime as determined from responses on the Sleep Diary
9. Confirmation of sufficient duration of time spent in bed, as determined from responses on the Sleep Diary

10. Objective (polysomnography [PSG]) evidence of insomnia as follows:

    a) Wake after sleep onset (WASO) average ≥ 60 minutes on the 2 consecutive PSGs, with neither night < 45 minutes

11. Willing and able to comply with all aspects of the protocol, including staying in bed for at least 7 hours each night
12. Willing not to start a behavioral or other treatment program for the treatment of insomnia during the participant's participation in the study

Exclusion Criteria

1. A current diagnosis of sleep-related breathing disorder including obstructive sleep apnea (with or without continuous positive airway pressure [CPAP] treatment), periodic limb movement disorder, restless legs syndrome, circadian rhythm sleep disorder, or narcolepsy, or an exclusionary score on screening instruments to rule out individuals with symptoms of certain sleep disorders other than insomnia as follows:

   1. STOPBang score ≥5
   2. International Restless Legs Scale score ≥16
   3. Epworth Sleepiness Scale score >15 (scores of 11 to 15 require excessive daytime sleepiness to be recorded in participant's Medical History)
2. Reports symptoms potentially related to narcolepsy, that in the clinical opinion of the investigator indicates the need for referral for a diagnostic evaluation for the presence of narcolepsy
3. On the Munich Parasomnia Scale (MUPS), endorsed the item that corresponds to a history of sleep-eating or reports a history of sleep-related violent behavior, sleep-driving, or symptoms of another parasomnia that in the investigator's opinion make the participant unsuitable for the study
4. Apnea-Hypopnea Index > 15 or Periodic Limb Movement with Arousal Index >15 as measured on the PSG at the second screening visit
5. Beck Depression Inventory - II (BDI-II) score >19 at Screening
6. Beck Anxiety Index (BAI) score >15 at Screening
7. Habitually naps during the day more than 3 times per week
8. Is a female of childbearing potential Note: All females will be considered to be of childbearing potential unless they are postmenopausal (defined as amenorrheic for at least 12 consecutive months, and are postmenopausal without other known or suspected cause), or have been sterilized surgically (i.e., bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing).
9. Excessive caffeine use that in the opinion of the investigator contributes to the participant's insomnia, or habitually consumes caffeine-containing beverages after 18:00 and is unwilling to forego caffeine after 18:00 for the duration of his/her participation in the study.
10. History of drug or alcohol dependency or abuse within approximately the previous 2 years
11. Reports habitually consuming more than 14 drinks containing alcohol per week (females) or more than 21 drinks containing alcohol per week (males), or unwilling to limit alcohol intake to no more than 2 drinks per day or forego having alcohol within the 3 hours before bedtime for the duration of his/her participation in the study
12. Known to be positive for human immunodeficiency virus
13. Active viral hepatitis (B or C) as demonstrated by positive serology at Screening
14. A prolonged QT/QTcF interval (QTcF >450 milliseconds [ms]) as demonstrated by a repeated electrocardiogram (ECG) at Screening (repeated only if initial ECG indicates a QTcF interval >450 ms)
15. Current evidence of clinically significant disease (e.g., cardiac; respiratory including chronic obstructive pulmonary disease, acute and/or severe respiratory depression; gastrointestinal; severe hepatic impairment; renal including severe renal impairment; neurological including myasthenia gravis; psychiatric disease; or malignancy within the past 5 years other than adequately treated basal cell carcinoma) or chronic pain that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments, including the ability to perform tasks on the cognitive performance assessment battery (PAB). Participants for whom a sedating drug would be contraindicated for safety reasons because of the participant's occupation or activities are also excluded.
16. Comorbid nocturia resulting in frequent need to get out of bed to use the bathroom during the night
17. Any history of a medical or psychiatric condition that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessment, including the ability to perform the PAB.
18. Any suicidal ideation with intent with or without a plan, at the time of or within 6 months before the electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) administration during the Prerandomization Phase (i.e., answering "Yes" to questions 4 or 5 on the Suicidal Ideation section of the eC-SSRS)
19. Any suicidal behavior in the past 10 years (per the Suicidal Behavior section of the eC-SSRS)
20. Scheduled for surgery during the study
21. Used any prohibited prescription or over-the-counter concomitant medications within 1 week or 5 half lives, whichever is longer, before the first dose of study medication (Run-in Period).
22. Used any modality of treatment for insomnia, including cognitive behavioral therapy or marijuana within 1 week or 5 half-lives, whichever is longer, before the first dose of study medication (Run-in Period)
23. Failed treatment with suvorexant (Belsomra®) (efficacy and/or safety) following treatment with an appropriate dose and of adequate duration in the opinion of the investigator
24. Transmeridian travel across more than 3 time zones in the 2 weeks before Screening, or between Screening and Baseline, or plans to travel across more than 3 time zones during the study
25. A positive drug test at Screening, Run-In, or Baseline, or unwilling to refrain from use of recreational drugs during the study
26. Hypersensitivity to lemborexant or zolpidem or to their excipients
27. Currently enrolled in another clinical trial or used any investigational drug or device within 30 days or 5× the half-life, whichever is longer preceding informed consent
28. Previously participated in any clinical trial of lemborexant

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lemborexant 5 milligrams (mg); Participants will receive one lemborexant 5 mg tablet and one zolpidem-matched placebo tablet each night	Drug: Lemborexant; Lemborexant 5 mg will be administered orally in tablet form at home each night, immediately before the time the participant intends to try to sleep.; Other Names: E2006; Drug: Lemborexant; Lemborexant 10 mg will be administered orally in tablet form at home each night, immediately before the time the participant intends to try to sleep.; Other Names: E2006; Drug: Zolpidem-matched placebo; Zolpidem-matched placebo will be administered orally in tablet form at home each night, immediately before the time the participant intends to try to sleep.
Experimental: Lemborexant 10 mg; Participants will receive one lemborexant 10 mg tablet and one zolpidem-matched placebo tablet each night	Drug: Lemborexant; Lemborexant 5 mg will be administered orally in tablet form at home each night, immediately before the time the participant intends to try to sleep.; Other Names: E2006; Drug: Lemborexant; Lemborexant 10 mg will be administered orally in tablet form at home each night, immediately before the time the participant intends to try to sleep.; Other Names: E2006; Drug: Zolpidem-matched placebo; Zolpidem-matched placebo will be administered orally in tablet form at home each night, immediately before the time the participant intends to try to sleep.
Active Comparator: Zolpidem tartrate; Participants will receive one zolpidem 6.25 mg tablet and one lemborexant-matched placebo tablet each night	Drug: Lemborexant-matched placebo; Lemborexant-matched placebo be administered orally in tablet form at home each night, immediately before the time the participant intends to try to sleep.; Drug: Zolpidem tartrate; Zolpidem tartrate extended release 6.25 mg will be administered orally in tablet form at home each night, immediately before the time the participant intends to try to sleep.; Other Names: Ambien CR
Placebo Comparator: Placebo; Participants will receive one zolpidem-matched placebo tablet and one lemborexant-matched placebo tablet each night	Drug: Zolpidem-matched placebo; Zolpidem-matched placebo will be administered orally in tablet form at home each night, immediately before the time the participant intends to try to sleep.; Drug: Lemborexant-matched placebo; Lemborexant-matched placebo be administered orally in tablet form at home each night, immediately before the time the participant intends to try to sleep.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean Latency to Persistent Sleep (LPS) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30	LPS is defined as the time in minutes from lights off to the first epoch of 20 consecutive epochs of non- wakefulness as measured by PSG. Change from baseline to average LPS on Day 29 and 30 was reported.	Baseline, Days 29/30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean Sleep Efficiency (SE) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30	SE is defined as percentage of time spent in bed asleep, calculated as total sleep time (TST) divided by interval from lights off until lights on as measured by PSG, multiplied by 100. Change from baseline to average SE on Day 29 and 30 was reported.	Baseline, Days 29/30
Change From Baseline in Mean Wake After Sleep Onset (WASO) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30	WASO is defined as minutes of wake from the onset of persistent sleep until lights on as measured by PSG. Change from baseline to average WASO on Days 29 and 30 was reported.	Baseline, Days 29/30
Change From Baseline in WASO in the Second Half of the Night (WASO2H) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 29/30	WASO2H is defined as time in minutes of wake during the interval from 240 minutes after lights off until lights on as measured by PSG. Change from baseline to average WASO2H on Days 29 and 30 was reported.	Baseline, Days 29/30

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean Body Sway Upon Awakening in the Morning for Lemborexant 5 mg and Lemborexant 10 mg Compared to Zolpidem ER on Days 2/3	Body sway is detected through a cable around the participant's waist by the ataxia meter. Body sway is measured in units of one-third degree of the angle of arc. For ease in reporting, these are called arbitrary units, with a higher number indicating more body sway (less postural stability). Change from baseline in mean body sway on Days 2 and 3 was reported.	Baseline, Days 2/3
Change From Baseline in Mean LPS, WASO, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER on Days 1/2 and Days 29/30	LPS is defined as the time in minutes from lights off to the first epoch of 20 consecutive epochs of non-wakefulness as measured by the PSG. WASO is defined as minutes of wake from the onset of persistent sleep until lights on as measured by PSG. TST is defined as the amount of sleep in minutes from LPS until terminal awakening as measured by PSG. Change from baseline to average LPS, WASO, and TST on Days 1 and 2, and Days 29 and 30 were reported.	Baseline, Days 1/2, and Days 29/30
Change From Baseline in Subjective Sleep Onset Latency (sSOL), Subjective Wake After Sleep Onset (sWASO) and Subjective Total Sleep Time (sTST) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER	sSOL: estimated minutes from time attempted to sleep to sleep onset. sWASO: estimated minutes of wake at night after initial sleep onset to time stopped trying to sleep for the night. sTST: minutes of sleep from sleep onset to time stopped trying to sleep for the night. sSOL, sWASO, sTST were analyzed with diary handling rules (DHR) on an electronic sleep diary. Subjective measures were derived from sleep diaries entries, collected daily and analyzed at appropriate intervals.	First 7 nights (approximately Week 1) and Last 7 nights (approximately Week 4)
Change From Baseline in Subjective Sleep Efficiency (sSE) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER	sSE: percentage of sTST per subjective time spent in bed asleep, calculated as the interval from the time attempted to sleep to time stopped trying to sleep for the night, and time spent asleep derived from subjective time spent in bed minus sWASO. sWASO: estimated minutes of wake at night after initial sleep onset to time stopped trying to sleep for the night. sSE was analyzed with DHR on an electronic sleep diary. Subjective measures were derived from sleep diaries entries, collected daily and analyzed at appropriate intervals.	First 7 nights (approximately Week 1) and Last 7 nights (approximately Week 4)
Change From Baseline in Mean LPS, WASO, WASO2H, and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2	LPS: amount of time in minutes from lights off to first epoch of 20 consecutive epochs of non-wakefulness. WASO: amount of time in minutes of wake from the onset of persistent sleep until lights. WASO2H: amount of time in minutes of wake during the interval from 240 minutes after lights off until lights on. TST: amount of time in minutes of sleep from sleep onset until terminal awakening. LPS, WASO, WASO2H, and TST were measured by PSG. Change from baseline to average LPS, WASO, WASO2H, and TST on Day 1 and 2 were reported.	Baseline, Days 1/2
Change From Baseline in Mean SE of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2	SE is defined as percentage of time spent in bed asleep, calculated as TST divided by interval from lights off until lights on as measured by PSG, multiplied by 100. Change from baseline to average SE on Day 1 and 2 were reported.	Baseline, Days 1/2
Change From Baseline in Mean WASO2H and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30	WASO2H is defined as the time in minutes of wake during the interval from 240 minutes after lights off until lights on. TST is defined as the amount of sleep in minutes from sleep onset until terminal awakening. WASO and TST were measured by PSG. Change from baseline to average WASO and TST on Day 29 and 30 were reported.	Baseline, Days 29/30
Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo	sSOL: estimated minutes from time attempted to sleep to sleep onset. sWASO: estimated minutes of wake at night after initial sleep onset to time stopped trying to sleep for the night. sTST: minutes of sleep from sleep onset to time stopped trying to sleep for the night. sSOL, sWASO, sTST were analyzed with DHR on an electronic sleep diary. Subjective measures were derived from sleep diaries entries, collected daily and analyzed at appropriate intervals.	First 7 nights (approximately Week 1) and Last 7 nights (approximately Week 4)
Change From Baseline in Mean sSE of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo	sSE: percentage of sTST per subjective time spent in bed asleep, calculated as the interval from the time attempted to sleep to time stopped trying to sleep for the night, and time spent asleep derived from subjective time spent in bed minus sWASO. sWASO: estimated minutes of wake at night after initial sleep onset to time stopped trying to sleep for the night. sSE was analyzed with DHR on an electronic sleep diary. Subjective measures were derived from sleep diaries entries, collected daily and analyzed at appropriate intervals.	First 7 nights (approximately Week 1) and Last 7 nights (approximately Week 4)
Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response	Objective sleep onset response: LPS less than or equal to (<=) 20 minutes (mins) provided baseline LPS was greater than (>) 30 mins. Subjective sleep onset response: sSOL <=20 mins provided mean baseline sSOL was >30 mins. Objective sleep maintenance response: WASO <=60 minutes provided baseline WASO was >60 mins and was reduced by >10 mins compared to baseline. Subjective sleep maintenance response: sWASO <=60 mins provided mean WASO was >60 mins and was reduced by >10 mins compared to baseline. Subjective measures were derived from sleep diaries entries, collected daily and analyzed at appropriate intervals. Average data for Days 1 and 2, Days 29 and 30, and first and last 7 nights of treatment period was reported.	Days 1/2, Days 29/30, first 7 night (approximately Week 1), and Last seven nights (approximately Week 4)
Change From Baseline in Score From Items 4 to 7 on the Insomnia Severity Index (ISI) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER and Placebo on Day 31	The ISI is a 7-item self-report questionnaire assessing the nature, severity, and impact of insomnia. The dimensions evaluated were: severity of sleep onset; sleep maintenance; early morning awakening problems; sleep dissatisfaction; interference of sleep difficulties with daytime functioning; noticeability of the sleep problems by others; and distress caused by the sleep difficulties. A 5-point Likert scale was used to rate each item (from 0 = no problem to 4 = very severe problem) yielding a total score from 0 to 28.	Baseline and Day 31
Change From Baseline in Fatigue Severity Scale (FSS) Score of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER and Placebo on Day 31	The FSS is a self-report scale on which participants are instructed to choose a number from 1 to 7 that indicates their degree of agreement with each of 9 statements about their fatigue where "1" indicates strongly disagree, and "7" indicates strongly agree. The FSS total score was the sum of all responses to the 9 questions. The FSS average item score was the average of the score for each item. Higher total scores and higher average item scores indicated greater fatigue.	Baseline and Day 31
Change From Baseline in Mean Power of Attention (POA) and Speed of Memory Retrieval (SOMT) on Days 2/3	POA reflects the ability to focus attention and process information. POA is calculated from the sum of simple reaction time, choice reaction time and digit vigilance. SOMT reflects time taken to retrieve information from working and episodic memory. SOMT is a composite score created by combining numerical working memory and spatial working memory and word recognition and picture recognition. Cognitive performance assessment was done by a computerized performance assessment battery (PAB) which was administered on a laptop computer. A positive change from baseline reflects impairment and a lower value of decrease from baseline indicates better performance. Change from baseline to average POA and SOMT on Days 2 and 3 was reported.	Baseline, Days 2/3
Change From Baseline in Mean Quality of Memory (QOM) and Continuity of Attention (COA) on Days 2/3	QOM represents the ability to store information in memory and subsequently retrieve it. It is a composite score created by combining accuracy measures from 2 sets of working memory and 4 sets of episodic memory. Two sets of working memory were included: numerical and spatial working memory, and ranges from -2 to 2. Four sets of episodic memory were included: immediate and delayed word recall, and word and picture recognition, and ranges from -200 to 400. COA is the ability to sustain attention. Number of correct responses (out of 50) for choice reaction time was added to total number of targets correctly identified (out of 45) digit vigilance minus number of false alarms (total score of -45 to 95). Higher values were better. Change from baseline to average QOM and COA on Days 2 and 3 was reported.	Baseline, Days 2/3

Collaborators and Investigators

• Sponsor: Eisai Inc.

Publications and helpful links

General Publications

• Chepke C, Jain R, Rosenberg R, Moline M, Yardley J, Pinner K, Kumar D, Perdomo C, Filippov G, Atkins N, Malhotra M. Improvement in fatigue and sleep measures with the dual orexin receptor antagonist lemborexant in adults with insomnia disorder. Postgrad Med. 2022 Apr;134(3):316-325. doi: 10.1080/00325481.2022.2049553. Epub 2022 Mar 20.
• Citrome L, Juday T, Frech F, Atkins N Jr. Lemborexant for the Treatment of Insomnia: Direct and Indirect Comparisons With Other Hypnotics Using Number Needed to Treat, Number Needed to Harm, and Likelihood to Be Helped or Harmed. J Clin Psychiatry. 2021 Jun 1;82:20m13795. doi: 10.4088/JCP.20m13795.
• Moline M, Zammit G, Cheng JY, Perdomo C, Kumar D, Mayleben D. Comparison of the effect of lemborexant with placebo and zolpidem tartrate extended release on sleep architecture in older adults with insomnia disorder. J Clin Sleep Med. 2021 Jun 1;17(6):1167-1174. doi: 10.5664/jcsm.9150.
• Rosenberg R, Murphy P, Zammit G, Mayleben D, Kumar D, Dhadda S, Filippov G, LoPresti A, Moline M. Comparison of Lemborexant With Placebo and Zolpidem Tartrate Extended Release for the Treatment of Older Adults With Insomnia Disorder: A Phase 3 Randomized Clinical Trial. JAMA Netw Open. 2019 Dec 2;2(12):e1918254. doi: 10.1001/jamanetworkopen.2019.18254. Erratum In: JAMA Netw Open. 2020 Apr 1;3(4):e206497. JAMA Netw Open. 2021 Aug 2;4(8):e2127643.

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2016
• Primary Completion (Actual): January 30, 2018
• Study Completion (Actual): January 30, 2018

Study Registration Dates

• First Submitted: May 24, 2016
• First Submitted That Met QC Criteria: May 24, 2016
• First Posted (Estimate): May 26, 2016

Study Record Updates

• Last Update Posted (Actual): February 11, 2020
• Last Update Submitted That Met QC Criteria: January 31, 2020
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Insomnia; Lemborexant; E2006; zolpidem tartrate; Ambien CR
• 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; Orexin Receptor Antagonists; GABA-A Receptor Agonists; GABA Agonists; Lemborexant; Zolpidem
• Other Study ID Numbers: E2006-G000-304; 2015-004347-39 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes