Clinical trial NCT02783729: Study of the Efficacy and Safety of Lemborexant in Subjects 55 Years and Older With Insomnia Disorder (SUNRISE 1)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Insomnia
Keywords: E2006
Lemborexant
zolpidem tartrate
Ambien CR
Insomnia
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2016-05-26
Enrollment: 1006
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Baseline, Days 29/30
Secondary outcomes:
measure: Change From Baseline in Mean Sleep Efficiency (SE) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30
timeFrame: Baseline, Days 29/30
measure: 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
timeFrame: Baseline, Days 29/30
measure: 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
timeFrame: Baseline, Days 29/30
Other outcomes:
measure: 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
timeFrame: Baseline, Days 2/3
measure: 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
timeFrame: Baseline, Days 1/2, and Days 29/30
measure: 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
timeFrame: First 7 nights (approximately Week 1) and Last 7 nights (approximately Week 4)
measure: Change From Baseline in Subjective Sleep Efficiency (sSE) of Lemborexant 10 mg and Lemborexant 5 mg Compared to Zolpidem ER
timeFrame: First 7 nights (approximately Week 1) and Last 7 nights (approximately Week 4)
measure: 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
timeFrame: Baseline, Days 1/2
measure: Change From Baseline in Mean SE of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 1/2
timeFrame: Baseline, Days 1/2
measure: Change From Baseline in Mean WASO2H and TST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo on Days 29/30
timeFrame: Baseline, Days 29/30
measure: Change From Baseline in Mean sSOL, sWASO, and sTST of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo
timeFrame: First 7 nights (approximately Week 1) and Last 7 nights (approximately Week 4)
measure: Change From Baseline in Mean sSE of Lemborexant 10 mg and Lemborexant 5 mg Compared to Placebo
timeFrame: First 7 nights (approximately Week 1) and Last 7 nights (approximately Week 4)
measure: Percentage of Responders With Objective and Subjective Sleep Onset Response, and Objective and Subjective Sleep Maintenance Response
timeFrame: Days 1/2, Days 29/30, first 7 night (approximately Week 1), and Last seven nights (approximately Week 4)
measure: 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
timeFrame: Baseline and Day 31
measure: 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
timeFrame: Baseline and Day 31
measure: Change From Baseline in Mean Power of Attention (POA) and Speed of Memory Retrieval (SOMT) on Days 2/3
timeFrame: Baseline, Days 2/3
measure: Change From Baseline in Mean Quality of Memory (QOM) and Continuity of Attention (COA) on Days 2/3
timeFrame: Baseline, Days 2/3
Locations:
city: Jasper
country: United States
facility: Jasper Summit Research LLC
state: Alabama
city: Glendale
country: United States
facility: PACT
state: Arizona
city: Little Rock
country: United States
facility: Preferred Research Partners
state: Arkansas
city: Carlsbad
country: United States
state: California
city: Fountain Valley
country: United States
facility: Southern California Research
state: California
city: Oceanside
country: United States
facility: Pacific Sleep Medicine Services
state: California
city: Oceanside
country: United States
facility: Research Center of Southern California
state: California
city: Orange
country: United States
facility: Orange County Neuropsychiatric Research Center, LLC
state: California
city: Orange
country: United States
facility: SDS Clinical Trials, Inc.
state: California
city: San Diego
country: United States
facility: Artemis Institute For Clinical Research LLC
state: California
city: San Diego
country: United States
facility: Pacific Research Network Inc
state: California
city: San Marcos
country: United States
facility: Artemis Institute For Clinical Research
state: California
city: Santa Monica
country: United States
facility: Santa Monica Clinical Trials
state: California
city: Upland
country: United States
facility: Empire Clinical Research
state: California
city: Brandon
country: United States
facility: PAB Clinical Research
state: Florida
city: Clearwater
country: United States
facility: Saint Francis Sleep Allergy and Lung Institute
state: Florida
city: Fleming Island
country: United States
facility: Fleming Island Center For Clinical Research
state: Florida
city: Gainesville
country: United States
facility: Sarkis Clinical Trials
state: Florida
city: Hallandale Beach
country: United States
facility: MD Clinical
state: Florida
city: Hollywood
country: United States
facility: QPS MRA
state: Florida
city: Miami
country: United States
facility: Quest Pharmaceutical Services-Miami Research Associates, LLC (QPS MRA)
state: Florida
city: Oakland Park
country: United States
facility: Research Centers of America
state: Florida
city: Orlando
country: United States
facility: Compass Research LLC
state: Florida
city: Panama City
country: United States
facility: NeuroMedical Research Institute
state: Florida
city: Saint Petersburg
country: United States
facility: Clinical Research Group of St Petersburg Inc
state: Florida
city: Atlanta
country: United States
facility: NeuroTrials Research Inc.
state: Georgia
city: Stockbridge
country: United States
facility: SleepCare Research Institute Inc
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Chicago Research Center Inc
state: Illinois
city: Chevy Chase
country: United States
facility: Helene A Emsellem MD PC
state: Maryland
city: Glen Burnie
country: United States
facility: Sleep Disorders Center of the Mid-Atlantic
state: Maryland
city: Newton
country: United States
facility: Neurocare Inc
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Novi
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Sterling Heights
country: United States
facility: Clinical Neurophysiology Services
state: Michigan
city: Saint Louis
country: United States
facility: St. Louis Clinical Trials
state: Missouri
city: Saint Louis
country: United States
facility: Clayton Sleep Institute
state: Missouri
city: Las Vegas
country: United States
facility: Clinical Research Center of Nevada
state: Nevada
city: Berlin
country: United States
facility: Hassman Research Institute
state: New Jersey
city: Eatontown
country: United States
facility: CLINiLABS, Inc.
state: New Jersey
city: Garden City
country: United States
facility: Winthrop University Hospital
state: New York
city: New York
country: United States
facility: Clinical Research Unit
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Staten Island
country: United States
facility: Richmond Behavioral Associates
state: New York
city: West Seneca
country: United States
facility: Sleep Medicine Centers of Western New York
state: New York
city: Raleigh
country: United States
facility: Wake Research Associates, LLC
state: North Carolina
city: Wilmington
country: United States
facility: Wilmington Health Associates
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Cincinnati
country: United States
facility: Intrepid Research
state: Ohio
city: Cincinnati
country: United States
facility: CTI Clinical Research Center
state: Ohio
city: Dublin
country: United States
facility: Ohio Sleep Medicine Institute
state: Ohio
city: Middleburg Heights
country: United States
facility: Cleveland Sleep Research Center
state: Ohio
city: Oklahoma City
country: United States
facility: Lynn Health Science Institute
state: Oklahoma
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina - PPDS
state: South Carolina
city: Columbia
country: United States
facility: Sleepmed of South Carolina
state: South Carolina
city: Houston
country: United States
facility: Pioneer Research Solutions
state: Texas
city: Vienna
country: United States
facility: Sleep Disorders Center of the Mid-Atlantic
state: Virginia
city: Seattle
country: United States
state: Washington
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Calgary
country: Canada
facility: Sleep and Fatigue Institute
state: Alberta
city: Kelowna
country: Canada
facility: Medical Arts Health Research Group
state: British Columbia
city: Markham
country: Canada
state: Ontario
city: Markham
country: Canada
facility: Somni Research Inc.
state: Ontario
city: Mississauga
country: Canada
facility: Tri Hospital Sleep West
state: Ontario
city: Scarborough
country: Canada
facility: Sleep Wake Disorders Clinic
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Toronto
country: Canada
facility: Toronto Sleep Institute
state: Ontario
city: Bordeaux
country: France
facility: Centre Hospitalier Universitaire de Bordeaux, Hopital Pellegrin
city: Clermont-ferrand
country: France
facility: Hopital Gabriel Montpied
city: Dijon Cedex
country: France
facility: CHU Dijon Bourgogne
city: Paris
country: France
facility: Hôtel Dieu de Paris Hospital
city: Strasbourg
country: France
facility: Hopital Civil
city: Mannheim
country: Germany
facility: Zentralinstitut für Seelische Gesundheit
state: Baden-Württemberg
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: Advanced Sleep Research GmbH
city: Berlin
country: Germany
facility: Emovis GmbH
city: Kassel
country: Germany
facility: Studienzentrum Wilhelmshöhe
city: München
country: Germany
facility: Klinikum rechts der Isar der Technischen Universität München
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Schwerin
country: Germany
facility: Somni Bene Institut für Medizinische Forschung und Schlafmedizin Schwerin GmbH
city: Bologna
country: Italy
facility: Ospedale Bellaria
state: Emilia-Romagna
city: Milan
country: Italy
facility: Ospedale San Raffaele S.r.l. - PPDS
state: Lombardia
city: Parma
country: Italy
facility: Azienda Ospedaliero Universitaria di Parma
city: Pavia
country: Italy
facility: ASST di Pavia - Fondazione Istituto Neurologico Mondino IRCCS
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: Roma
country: Italy
facility: Fondazione PTV Policlinico Tor Vergata
city: Torino
country: Italy
facility: Azienda Ospedaliera Città della Salute e della Scienza di Torino
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
city: Badalona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
city: Barcelona
country: Spain
facility: Clinica del Son Estivill
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu i Sant Pau
city: La Coruña
country: Spain
facility: Hospital San Rafael
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Instituto de Investigaciones del Sueño
city: Vitória
country: Spain
facility: Hospital Universitario Araba - Txagorritxu
city: Cambridge
country: United Kingdom
facility: Papworth Hospital
state: Cambridge Shire
city: Guildford
country: United Kingdom
facility: University of Surrey
state: Surrey
city: London
country: United Kingdom
facility: Guys Hospital
city: Stoke on Trent
country: United Kingdom
facility: Royal Stoke University Hospital
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.