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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02952820




Registration number
NCT02952820
Ethics application status
Date submitted
31/10/2016
Date registered
2/11/2016
Date last updated
6/02/2020

Titles & IDs
Public title
Long-term Study of Lemborexant in Insomnia Disorder (SUNRISE 2)
Scientific title
A Long-Term Multicenter, Randomized, Double-Blind, Controlled, Parallel Group Study of the Safety and Efficacy of Lemborexant in Subjects With Insomnia Disorder (SUNRISE 2)
Secondary ID [1] 0 0
2015-001463-39
Secondary ID [2] 0 0
E2006-G000-303
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Insomnia Disorder 0 0
Condition category
Condition code
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: lemborexant 5 milligrams (mg) - Lemborexant 5 mg will be taken orally in tablet form at home each night immediately before the time the participant intends to try to sleep.

Experimental: lemborexant 10 mg - Lemborexant 10 mg will be taken orally in tablet form at home each night immediately before the time the participant intends to try to sleep.

Placebo comparator: Placebo matched to lemborexant - Lemborexant-matched placebo will be taken orally in tablet form at home each night immediately before the time the participant intends to try to sleep.
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Subjective Sleep Onset Latency (sSOL) at Month 6
Timepoint [1] 0 0
Baseline and Month 6
Secondary outcome [1] 0 0
Change From Baseline in sSOL at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1 and 3
Timepoint [1] 0 0
Baseline, (mean of 7 nights [approximately Week 1]), Months 1 and 3
Secondary outcome [2] 0 0
Change From Baseline in Subjective Sleep Efficiency (sSE) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6
Timepoint [2] 0 0
Baseline, (mean of 7 nights [approximately Week 1]), Months 1, 3 and 6
Secondary outcome [3] 0 0
Change From Baseline in Subjective Wake After Sleep Onset (sWASO) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6
Timepoint [3] 0 0
Baseline, (mean of 7 nights [approximately Week 1]), Months 1, 3 and 6
Secondary outcome [4] 0 0
Change From Baseline in sTST at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6
Timepoint [4] 0 0
Baseline, (mean of 7 nights [approximately Week 1]), Months 1, 3 and 6
Secondary outcome [5] 0 0
Percentage of Sleep Onset Responders and Sleep Maintenance Responders at Month 6
Timepoint [5] 0 0
Month 6
Secondary outcome [6] 0 0
Percentage of Sleep Onset Responders and Sleep Maintenance Responders at Month 12
Timepoint [6] 0 0
Month 12
Secondary outcome [7] 0 0
Change From Baseline in Insomnia Severity Index (ISI) Daytime Functioning Score at Months 1, 3, and 6
Timepoint [7] 0 0
Baseline, Months 1, 3, and 6
Secondary outcome [8] 0 0
Change From Baseline in Fatigue Severity Scale (FSS) Total Score at Months 1, 3 and 6
Timepoint [8] 0 0
Baseline, Months 1, 3 and 6
Secondary outcome [9] 0 0
Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6
Timepoint [9] 0 0
Baseline, (mean of 7 nights [approximately Week 1]) in placebo-controlled period, Month 1, 3, 6
Secondary outcome [10] 0 0
Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Active Treatment Period)
Timepoint [10] 0 0
Baseline, First 7 nights (approximately Week 1) in active treatment period
Secondary outcome [11] 0 0
Change From Screening in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the First and Second 7 Mornings of the Follow-up Period
Timepoint [11] 0 0
Screening, First and second 7 mornings in follow-up period (Week 52 to 54)
Secondary outcome [12] 0 0
Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at Months 1, 3, 6, 9 and 12
Timepoint [12] 0 0
Baseline, Months 1, 3, 6, 9 and 12
Secondary outcome [13] 0 0
Rebound Insomnia: Mean sSOL on Each of the First 3 Nights, First 7 Nights, and Last 7 Nights of the Follow-up Period
Timepoint [13] 0 0
First 3 nights, first and Last 7 nights of the follow up period (Week 52 to 54)
Secondary outcome [14] 0 0
Rebound Insomnia: Mean sWASO on Each of the First 3 Nights, First 7 Nights, and Last 7 Nights of the Follow-up Period
Timepoint [14] 0 0
First 3 nights, first and last 7 nights of the follow up period (Week 52 to 54)
Secondary outcome [15] 0 0
Rebound Insomnia: Percentage of Participants Whose sSOL Was Longer Than at Screening for First 3 Nights of the Follow-up Period, or Whom Mean sSOL Was Longer Than at Screening for First 7 Nights or Last 7 Nights of the Follow-up Period
Timepoint [15] 0 0
First 3 nights, first and last 7 nights of the follow up period (Week 52 to 54)
Secondary outcome [16] 0 0
Rebound Insomnia: Percentage of Participants Whose sWASO is Higher Than at Screening for First 3 Nights of the Follow-up Period, or Whose Mean sWASO is Higher Than at Screening for the First 7 Nights or Last 7 Nights of the Follow-up Period
Timepoint [16] 0 0
First 3 nights, First and Last 7 nights of the follow up period (Week 52 to 54)
Secondary outcome [17] 0 0
Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1
Timepoint [17] 0 0
Baseline, Month 1, 3, 6, 9, 12
Secondary outcome [18] 0 0
Persistence of Effect: Mean Change From Baseline in sSE at Months 3, 6, 9, and 12 Compared to Month 1
Timepoint [18] 0 0
Baseline, Months 1, 3, 6, 9, and 12
Secondary outcome [19] 0 0
Persistence of Effect: Mean Change From Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 9 and 12 Compared to Month 7
Timepoint [19] 0 0
Baseline, Month 7, 9, 12
Secondary outcome [20] 0 0
Persistence of Effect: Mean Change From Period 2 Baseline (Month 6) in sSE at Months 9 and 12 Compared to Month 7
Timepoint [20] 0 0
Baseline, Month 7, 9, 12
Secondary outcome [21] 0 0
Persistence of Effect: Mean Change From Study Baseline and Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 3 and 6 Exposure Compared to Month 1
Timepoint [21] 0 0
Baseline, Month 1, 3, 6
Secondary outcome [22] 0 0
Persistence of Effect: Mean Change From Study Baseline and Period 2 Baseline (Month 6) in sSE at Months 3 and 6 Exposure Compared to Month 1
Timepoint [22] 0 0
Baseline, Month 1, 3, 6

Eligibility
Key inclusion criteria
* Male or female, age 18 years or older at the time of informed consent
* Meets the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM 5) criteria for Insomnia Disorder, as follows:

* Complains of dissatisfaction with nighttime sleep in the form of difficulty getting to sleep, difficulty staying asleep, and/or awakening earlier in the morning than desired despite adequate opportunity for sleep
* Frequency of complaint =3 times per week
* Duration of complaint =3 months
* Associated with complaint of daytime impairment
* History of (Subjective Sleep Onset Latency) sSOL =30 minutes on at least 3 nights per week in the previous 4 weeks and/or subjective Wake after Sleep Onset (sWASO) =60 minutes on at least 3 nights per week in the previous 4 weeks
* History of regular time spent in bed, either sleeping or trying to sleep, between 7 and 9 hours
* Regular bedtime, between 21:00 and 01:00 and regular wake time, the time the participant gets out of bed for the day, between 05:00 and 10:00
* Insomnia Severity Index (ISI) score =15
* Confirmation of current insomnia symptoms as determined from the Sleep Diary completed on at least 7 consecutive mornings (minimum 5 of 7 for eligibility), such that sSOL =30 minutes on at least 3 of the 7 nights and/or sWASO =60 minutes on at least 3 of the 7 nights
* Confirmation of time spent in bed, as determined from on the Sleep Diary completed on 7 mornings between the first and second screening visit, such that there are not more than 2 nights with duration of time spent in bed 7 hours and 10 hours
* Confirmation of regular bedtimes and wake times such that the participant has a regular time spent in bed, either sleeping or trying to sleep, between 7 and 10 hours for the final 7 nights of the before visit 3.
* Confirmation of regular bedtime between 21:00 and 01:00 and time of getting out of bed for the day between 05:00 and 10:00 for the final 7 nights of the before visit 3.
* Willing and able to comply with all aspects of the protocol, including staying in bed for at least 7 hours each night
* Willing to not start a behavioral or other treatment program for insomnia during the participants participation in the study
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* A current diagnosis of sleep-related breathing disorder, periodic limb movement disorder, restless legs syndrome, circadian rhythm sleep disorder, or an exclusionary score on screening instruments to rule out individuals with symptoms of certain sleep disorders other than insomnia.

* STOPBang score greater than or equal to (>=) 5
* International Restless Legs Scale (IRLS) score >=16
* Epworth Sleepiness Scale (ESS) score >15
* 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
* Reports a history of sleep-related violent behavior, or sleep driving, or any other complex sleep-related behavior, eg, making phone calls, or preparing and eating food while asleep
* For participants who underwent polysomnography (PSG) within the previous year:

* Age 18 to 64 years: Apnea Hypopnea Index =10, or Periodic Limb Movements with Arousal Index =10
* Age =65 years: Apnea Hypopnea Index >15, or Periodic Limb Movements with Arousal Index >15
* Beck Depression Inventory - II (BDI II) score >19 at Screening
* Beck Anxiety Inventory (BAI) score >15 at Screening
* Habitually naps more than 3 times per week
* Females who are breastfeeding or pregnant at Screening or Study Baseline
* Females of childbearing potential who are not practicing acceptable pregnancy prevention methods (NOTE: All females will be considered to be of childbearing potential unless they are postmenopausal or have been sterilized surgically.)
* 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
* History of drug or alcohol dependency or abuse within approximately the previous 2 years
* 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
* A prolonged QT/QT interval corrected by Fridericia's formula (QTcF >450 ms) as demonstrated by a repeated electro cardiogram(ECG) at Screening (repeated only if initial ECG indicates a QTcF interval >450 ms)
* Current evidence of clinically significant disease (e.g., cardiac, respiratory, gastrointestinal, renal, neurological [including participants who lack capacity and/or whose cognitive decline indicates disorientation to person/place/time and/or situation], or psychiatric disease or malignancy other than 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
* Comorbid nocturia resulting in frequent need to get out of bed to use the bathroom during the night
* Scheduled for major surgery during the study
* Used any prohibited prescription or over-the-counter concomitant medications within 1 week before the first dose of study medication
* Used any modality of treatment for insomnia, including cognitive behavioral therapy or marijuana within 2 weeks before Screening
* 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
* Transmeridian travel across more than 3 time zones in the 2 weeks before Screening, or between Screening and Study Baseline
* Previously participated in any clinical trial of lemborexant

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/11/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
8/01/2019
Sample size
Target
Accrual to date
Final
971
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
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United States of America
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Arizona
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Arkansas
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California
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Colorado
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Florida
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Indiana
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Maryland
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Massachusetts
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Missouri
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New Mexico
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New York
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North Carolina
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Ohio
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Oklahoma
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Oregon
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Rhode Island
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Tennessee
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Texas
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Washington
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Canada
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British Columbia
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Canada
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Ontario
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Canada
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Quebec
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Finland
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Oulun Laani
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Finland
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Helsinki
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Finland
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Kuopio
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Finland
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Tampere
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Finland
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Turku
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Germany
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Nordrhein-Westfalen
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Germany
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Sachsen
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Germany
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Berlin
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Germany
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Hamburg
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Germany
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Hannover
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Italy
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Lombardia
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Italy
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Toscana
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Italy
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Roma
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Japan
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Gunma
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Japan
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Hokkaido
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Japan
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Kanagawa
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Japan
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Saitama
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Japan
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Tokyo
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Korea, Republic of
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Gyeonggido
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Korea, Republic of
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Daegu
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Korea, Republic of
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Seoul
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Mexico
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Nuevo Leon
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New Zealand
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North Island
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New Zealand
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South Island
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New Zealand
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Auckland
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New Zealand
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Rotorua
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Poland
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Malopolskie
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Poland
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Mazowieckie
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Poland
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Gdansk
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Katowice
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Ostroda
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Warszawa
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Romania
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Brasov
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Romania
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Bucharest
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Romania
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Constanta
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Romania
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Sibiu
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Romania
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Targu Mures
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Spain
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Baleares
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Spain
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Madrid
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Spain
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Valencia
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Spain
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Barcelona

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Eisai Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The key objectives of this study are to determine, using sleep diaries, whether lemborexant at the doses 5 milligrams (mg) and 10 mg is superior to placebo on subjective sleep onset, subjective sleep efficiency, and subjective sleep maintenance in participants with insomnia disorder.
Trial website
https://clinicaltrials.gov/study/NCT02952820
Trial related presentations / publications
Dash A, Pinner K, Inoue Y, Hayashida K, Lim SC, Yun CH, Lan TH, Huang CL, Yardley J, Kubota N, Moline M. Efficacy and safety of lemborexant over 12 months in Asian adults with insomnia disorder. Sleep Med X. 2022 Mar 24;4:100044. doi: 10.1016/j.sleepx.2022.100044. eCollection 2022 Dec.
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.
Roth T, Rosenberg R, Morin CM, Yardley J, Pinner K, Perdomo C, Atkins N Jr, Pappadopulos E, Malhotra M, Moline M. Impact of lemborexant treatment on insomnia severity: analyses from a 12-month study of adults with insomnia disorder. Sleep Med. 2022 Feb;90:249-257. doi: 10.1016/j.sleep.2022.01.024. Epub 2022 Feb 8.
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.
Yardley J, Karppa M, Inoue Y, Pinner K, Perdomo C, Ishikawa K, Filippov G, Kubota N, Moline M. Long-term effectiveness and safety of lemborexant in adults with insomnia disorder: results from a phase 3 randomized clinical trial. Sleep Med. 2021 Apr;80:333-342. doi: 10.1016/j.sleep.2021.01.048. Epub 2021 Feb 1.
Inoue Y, Watanabe T, Takashima S, Takase T, Ishikawa K, Kubota N, Yardley J, Moline M. Efficacy and safety of lemborexant in adults with insomnia: comparing Japanese and non-Japanese subgroups from the global, phase 3, randomized, double-blind, placebo-controlled SUNRISE 2 study. J Clin Sleep Med. 2021 May 1;17(5):1067-1074. doi: 10.5664/jcsm.9148.
Karppa M, Yardley J, Pinner K, Filippov G, Zammit G, Moline M, Perdomo C, Inoue Y, Ishikawa K, Kubota N. Long-term efficacy and tolerability of lemborexant compared with placebo in adults with insomnia disorder: results from the phase 3 randomized clinical trial SUNRISE 2. Sleep. 2020 Sep 14;43(9):zsaa123. doi: 10.1093/sleep/zsaa123.
Public notes

Contacts
Principal investigator
Name 0 0
Eisai Medical Information
Address 0 0
Eisai Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02952820