Long-term Study of Lemborexant in Insomnia Disorder (SUNRISE 2)

NCT ID: NCT02952820

Last Updated: 2020-02-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 971 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-15
• Study Completion Date: 2019-01-08

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.

Detailed Description

This is a long-term (approximately 1 year), multicenter, randomized, controlled, double-blind, parallel group study of two doses of lemborexant and placebo in approximately 900 male or female participants with insomnia disorder. Approximately 40% of participants will be age 65 years or older. The study will last a maximum of 60 weeks, and will include a Screening Period, an approximately 54-week Treatment Period (during which study medication will be administered), and a 2-week Follow-up Period. All participants will receive lemborexant for at least 6 months and will receive placebo at some point during the study. Participants will not know which medication they receive (lemborexant or placebo) until the study has been completed, and will not know the timings at which the medication will change.

Conditions

Insomnia Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

lemborexant

Intervention Type: DRUG

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.

Group Type: EXPERIMENTAL

lemborexant

Intervention Type: DRUG

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

lemborexant

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eisai Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Eisai Medical Information

Role: STUDY_DIRECTOR

Eisai Inc.

Locations

Facility # 1

Chandler, Arizona, United States

Facility # 2

Chandler, Arizona, United States

Facility # 1

Rogers, Arkansas, United States

Facility # 1

Beverly Hills, California, United States

Facility # 2

Los Angeles, California, United States

Facility # 1

Los Angeles, California, United States

Facility # 1

Redlands, California, United States

Facility # 1

Sacramento, California, United States

Facility # 1

Santa Monica, California, United States

Facility # 1

Torrance, California, United States

Facility # 1

Colorado Springs, Colorado, United States

Facility # 1

Celebration, Florida, United States

Facility # 1

Hialeah, Florida, United States

Facility # 1

Homestead, Florida, United States

Facility # 1

Jacksonville, Florida, United States

Facility # 1

Lauderhill, Florida, United States

Facility # 1

Maitland, Florida, United States

Innovative Clinical Research Inc

Miami, Florida, United States

Facility # 1

Ocala, Florida, United States

Facility # 1

Orlando, Florida, United States

Facility # 1

Oviedo, Florida, United States

Facility # 1

Pinellas Park, Florida, United States

Facility # 1

Tampa, Florida, United States

Facility # 1

The Villages, Florida, United States

Facility # 1

Evansville, Indiana, United States

Facility # 1

Elkridge, Maryland, United States

Facility # 1

Quincy, Massachusetts, United States

Facility # 1

Kansas City, Missouri, United States

Facility # 1

Albuquerque, New Mexico, United States

Facility # 1

Brooklyn, New York, United States

Facility # 1

Hickory, North Carolina, United States

Facility # 1

Dayton, Ohio, United States

Facility # 2

Oklahoma City, Oklahoma, United States

Facility # 1

Oklahoma City, Oklahoma, United States

Facility # 1

Portland, Oregon, United States

Facility # 1

Lincoln, Rhode Island, United States

Facility # 1

Memphis, Tennessee, United States

Facility # 1

Austin, Texas, United States

Facility # 2

Austin, Texas, United States

Facility # 1

Fort Worth, Texas, United States

Facility # 1

San Angelo, Texas, United States

Facility # 1

Seattle, Washington, United States

Facility # 1

Kelowna, British Columbia, Canada

Facility # 1

Toronto, Ontario, Canada

Facility # 1

Point-Claire, Quebec, Canada

Facility # 1

Sherbrooke, Quebec, Canada

Facility # 1

Oulu, Oulun Laani, Finland

Facility # 1

Helsinki, , Finland

Facility # 1

Kuopio, , Finland

Facility # 1

Tampere, , Finland

Facility # 1

Turku, , Finland

Facility # 2

Turku, , Finland

Facility # 1

Bochum, North Rhine-Westphalia, Germany

Facility # 1

Leipzig, Saxony, Germany

Facility # 1

Berlin, , Germany

Facility # 2

Berlin, , Germany

Facility # 3

Berlin, , Germany

Facility # 1

Hamburg, , Germany

Facility # 1

Hanover, , Germany

Facility # 1

Milan, Lombardy, Italy

Facility # 1

Siena, Tuscany, Italy

Facility # 1

Roma, , Italy

Eisai Trail Site 1

Maebashi, Gunma, Japan

Eisai Trail Site 1

Sapporo, Hokkaido, Japan

Eisai Trail Site 2

Sapporo, Hokkaido, Japan

Eisai Trail Site 3

Sapporo, Hokkaido, Japan

Eisai Trail Site 4

Sapporo, Hokkaido, Japan

Eisai Trail Site 1

Sagamihara, Kanagawa, Japan

Eisai Trial Site 1

Yokohama, Kanagawa, Japan

Eisai Trial Site 2

Yokohama, Kanagawa, Japan

Eisai Trial Site 3

Yokohama, Kanagawa, Japan

Eisai Trail Site 1

Tokorozawa, Saitama, Japan

Eisai Trail Site 1

Arakawa City, Tokyo, Japan

Eisai Trail Site 1

Katsushika-ku, Tokyo, Japan

Eisai Trail Site 1

Minato, Tokyo, Japan

Eisai Trail Site 2

Minato, Tokyo, Japan

Eisai Trail Site 1

Musashino, Tokyo, Japan

Eisai Trail Site 1

Ōta-ku, Tokyo, Japan

Eisai Trail Site 2

Ōta-ku, Tokyo, Japan

Eisai Trail Site 3

Ōta-ku, Tokyo, Japan

Eisai Trail Site 1

Shibuya City, Tokyo, Japan

Eisai Trail Site 1

Shinagawa, Tokyo, Japan

Eisai Trail Site 2

Shinagawa, Tokyo, Japan

Eisai Trail Site 1

Shinjuku, Tokyo, Japan

Eisai Trail Site 2

Shinjuku, Tokyo, Japan

Eisai Trail Site 1

Toshima City, Tokyo, Japan

Facility # 1

Monterrey, Nuevo León, Mexico

Facility # 1

Wellington, North Island, New Zealand

Facility # 1

Christchurch, South Island, New Zealand

Facility # 1

Dunedin, South Island, New Zealand

Facility # 1

Auckland, , New Zealand

Facility # 1

Rotorua, , New Zealand

Facility # 1

Tarnów, Lesser Poland Voivodeship, Poland

Facility # 1

Warsaw, Masovian Voivodeship, Poland

Facility # 1

Gdansk, , Poland

Facility # 1

Katowice, , Poland

Facility # 1

Ostróda, , Poland

Facility # 2

Warsaw, , Poland

Facility # 3

Warsaw, , Poland

Facility # 1

Brasov, , Romania

Facility # 1

Bucharest, , Romania

Facility # 1

Constanța, , Romania

Facility # 1

Sibiu, , Romania

Facility # 1

Târgu Mureş, , Romania

Facility # 1

Seongnam-si, Gyeonggido, South Korea

Facility # 1

Suwon, Gyeonggido, South Korea

Facility # 1

Daegu, , South Korea

Facility # 1

Seoul, , South Korea

Facility # 3

Seoul, , South Korea

Facility # 1

Palma de Mallorca, Balearic Islands, Spain

Facility # 1

Torrejón de Ardoz, Madrid, Spain

Facility # 1

Quart de Poblet, Valencia, Spain

Facility # 1

Barcelona, , Spain

Facility # 1

Valencia, , Spain

Countries

United States; Canada; Finland; Germany; Italy; Japan; Mexico; New Zealand; Poland; Romania; South Korea; Spain

References

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Reference Type: DERIVED

PMID: 39823487 (View on PubMed)

Arnold V, Ancoli-Israel S, Dang-Vu TT, Mishima K, Pinner K, Malhotra M, Moline M. Efficacy of Lemborexant in Adults >/= 65 Years of Age with Insomnia Disorder. Neurol Ther. 2024 Aug;13(4):1081-1098. doi: 10.1007/s40120-024-00622-9. Epub 2024 May 15.

Reference Type: DERIVED

PMID: 38748321 (View on PubMed)

Citrome L, Juday TR, Lundwall C. Lemborexant and Daridorexant for the Treatment of Insomnia: An Indirect Comparison Using Number Needed to Treat, Number Needed to Harm, and Likelihood to Be Helped or Harmed. J Clin Psychiatry. 2023 Oct 2;84(6):23m14851. doi: 10.4088/JCP.23m14851.

Reference Type: DERIVED

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Terauchi M, Cheng JY, Yardley J, Pinner K, Moline M, Malhotra M, Inabe K, Nishida M, Pappadopulos E. Efficacy and safety of lemborexant in midlife women with insomnia disorder. Menopause. 2023 Aug 1;30(8):839-848. doi: 10.1097/GME.0000000000002209. Epub 2023 Jun 20.

Reference Type: DERIVED

PMID: 37339396 (View on PubMed)

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.

Reference Type: DERIVED

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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.

Reference Type: DERIVED

PMID: 35254948 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35220140 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34077032 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33636648 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33576735 (View on PubMed)

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.

Reference Type: DERIVED

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Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-001463-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

E2006-G000-303

Identifier Type: -

Identifier Source: org_study_id