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CompletedNCT04549168Updated Dec 20, 2024Results posted

A Study of Lemborexant in Chinese Participants With Insomnia Disorder

A Phase 3 interventional study of Lemborexant and Placebo in Sleep Initiation and Maintenance Disorders, sponsored by Eisai Co., Ltd.. Completed at 23 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-12-20.

Sponsored by Eisai Co., Ltd. · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
194
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

The primary purpose of this study is to confirm using polysomnography (PSG) that lemborexant 10 milligram (mg) is superior to placebo on objective sleep onset as assessed by latency to persistent sleep (LPS) during the last 2 nights of 1 month of treatment in participants with insomnia disorder.

Read the detailed description

The study will have 2 phases: the Prerandomization Phase and the Randomization Phase. The Prerandomization Phase will comprise 3 periods that will last up to a maximum of 35 days: a Screening Period, a Run-in Period, and a Baseline Period. The Randomization Phase will comprise a Treatment Period during which participants will be treated for 30 nights (1 month) and a minimum 14-day Follow-up Period before an End of Study (EOS) Visit (up to 54 days). The total study duration for each participant on this study is 89 days.

02

Conditions studied

  • Sleep Initiation and Maintenance Disorders

Keywords

  • Insomnia disorder
  • Lemborexant
  • Chinese Participants
  • E2006
03

In context

Sleep Initiation and Maintenance Disorders

1,856 studies on the registry are indexed under Sleep Initiation and Maintenance Disorders; 594 are open to participants now.

This study's enrollment of 194 is above the median of 73 across 1,631 interventional studies indexed under Sleep Initiation and Maintenance Disorders.

Browse Sleep Initiation and Maintenance Disorders studies →

Lead sponsor

Eisai Co., Ltd. is the lead sponsor of 149 studies on the registry; 5 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

Participants must meet all of the following criteria to be included in this study:

  1. Chinese male or female, age 18 years or older, at the time of informed consent (in Taiwan only participants with age 20 years or older are eligible)

  2. Meets the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for Insomnia Disorder, as follows:

    • Complains of dissatisfaction with night time sleep, in the form of difficulty staying asleep and/or awakening earlier in the morning than desired despite adequate opportunity for sleep
    • Frequency of complaint greater than or equal to (>=) 3 times per week
    • Duration of complaint >=3 months
    • Associated with complaint of daytime impairment
  3. At Screening: History of sSOL >=30 minutes on at least 3 nights per week in the previous 4 weeks and/or sWASO >=60 minutes on at least 3 nights per week in the previous 4 weeks
  4. At Screening: Reports regular time spent in bed, either sleeping or trying to sleep, between 7 and 9 hours
  5. At second Screening Visit (Visit 2a) and Run-in Visit (Visit 3a): Sleep diary confirms regular bedtime, defined as the time the participant attempts to sleep, between 21:00 and 01:00 on at least 5 of the final 7 nights and regular waketime, defined as the time the participant gets out of bed for the day, between 05:00 and 10:00 on at least 5 of the final 7 nights
  6. At Screening and Baseline: ISI score >=15
  7. Confirmation of current insomnia symptoms, as determined from responses on the sleep diary on the 7 most recent mornings before the first PSG during Screening Period (Visit 2a) and Run-in visit (Visit 3a), 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
  8. At the second Screening Visit (Visit 2a) and the Run-in visit (Visit 3a): Confirmation of sufficient duration of time spent in bed, as determined from responses on the sleep diary on the 7 most recent mornings before the Visit, such that there are no more than 2 nights with time spent in bed duration less than (\<) 7 hours or greater than (>) 10 hours

  9. During the Run-in Period, objective (PSG) evidence of insomnia as follows:

    1. LPS average >=30 minutes on the 2 consecutive Baseline PSGs, with neither night \<20 minutes and/or
    2. WASO average >=60 minutes on the two consecutive Baseline PSGs, with neither night \<45 minutes
  10. Willing and able to comply with all aspects of the protocol, including staying in bed for at least 7 hours each night
  11. 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

Exclusion Criteria:

Participants who meet any of the following criteria will be excluded from this study:

  1. Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin test). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug

  2. Females of childbearing potential who: Within 28 days before study entry, did not use a highly effective method of contraception, which includes any of the following:

    • total abstinence (if it is their preferred and usual lifestyle)
    • an intrauterine device or intrauterine hormone-releasing system
    • a contraceptive implant
    • an oral contraceptive (participant must be on a stable dose of the same oral contraceptive product for at least 28 days before dosing and throughout the study and for 28 days after study drug discontinuation)
    • have a vasectomized partner with confirmed azoospermia
    • do not agree to use a highly effective method of contraception (as described above) throughout the entire study period and for 28 days after study drug discontinuation It is permissible that if a highly effective method of contraception is not appropriate or acceptable to the participant, then the participant must agree to use a medically acceptable method of contraception, that is, double-barrier methods of contraception such as latex or synthetic condom plus diaphragm or cervical/vault cap with spermicide NOTE: All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (that is, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing)
  3. 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 assessments
  4. A prolonged corrected QT interval by Fredericia's formula (QTcF) interval (QTcF >450 millisecond [ms]) as demonstrated by a repeated electrocardiogram. A history of risk factors for torsade de pointes (for example, heart failure, hypokalemia, family history of long QT Syndrome) or the use of concomitant medications that prolonged the QTcF interval
  5. Any suicidal ideation with intent with or without a plan at Screening or within 6 months of Screening
  6. Any suicidal behavior in the past 10 years
  7. Evidence of clinically significant disease (for example, cardiac; respiratory including chronic obstructive pulmonary disease, acute and/or severe respiratory depression; gastrointestinal; moderate and 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. Participants for whom a sedating drug would be contraindicated for safety reasons because of the participant's occupation or activities are also excluded
  8. Hypersensitivity to lemborexant or to their excipients
  9. Scheduled for surgery during the study
  10. Known to be human immunodeficiency virus positive
  11. Active viral hepatitis (B or C) as demonstrated by positive serology
  12. History of drug or alcohol dependency or abuse within approximately the last 2 years

  13. A current diagnosis of sleep-related breathing disorder including obstructive sleep apnea (with or without continuous positive airway pressure 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:

    • Snoring, Tiredness, Observed apnea, high blood Pressure (STOP)-Body mass index (BMI), Age, Neck circumference, and Gender (BANG) score >=5
    • International Restless Legs Scale score >=16
  14. Apnea-hypopnea Index >15 or Periodic Limb Movement with Arousal Index >15 as measured on the PSG at the second Screening Visit
  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
  16. Reports a history of sleep-related violent behavior, or sleep driving, or any other complex sleep-related behavior (for example, making phone calls or preparing and eating food while sleeping)

  17. For participants who underwent diagnostic PSG within 1 year before informed consent:

    • 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
  18. Beck Depression Inventory-II score >19 at Screening
  19. Beck Anxiety Inventory score >15 at Screening
  20. Habitually naps during the day more than 3 times per week
  21. 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. Participants are excluded if, in the previous 3 months, they had symptoms that would meet DSM-5 criteria for caffeine intoxication, which includes consumption of a high dose of caffeine (significantly in excess of 250 mg) and >=5 of the following symptoms: restlessness, nervousness, excitement, insomnia, flushed face, diuresis, gastrointestinal disturbance, muscle twitching, rambling flow of thought and speech, tachycardia or cardiac arrhythmia, periods of high energy, or psychomotor agitation. To be exclusionary, those symptoms must cause distress or impairment in social, occupational and other forms of functioning, and not be associated with other substance, mental disorder or medical condition
  22. 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
  23. Excluding comorbid nocturia that is causing or exacerbating the insomnia
  24. 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)
  25. 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)
  26. Failed treatment with dual orexin receptor antagonist drugs (efficacy and/or safety) following treatment with an appropriate dose and of adequate duration in the opinion of the investigator
  27. 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 (China mainland will be considered as 1 time zone)
  28. A positive drug test at Screening, Run-in, or Baseline, or unwilling to refrain from use of recreational drugs during the study
  29. Currently enrolled in another clinical trial or used any investigational drug or device within 30 days or 5 half-lives, whichever is longer preceding informed consent
  30. Previously participated in any clinical trial of lemborexant
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
194 participants (actual)

Study arms

  • Experimental
    Lemborexant 10 mg

    Participants will receive one lemborexant 10 mg tablet, orally, once daily for 30 consecutive nights on each night approximately 5 minutes before participants intends to try to sleep.

    Drug: Lemborexant

  • Placebo comparator
    Placebo

    Participants will receive one placebo matched to lemborexant 10 mg tablet, orally, once daily for 30 consecutive nights on each night approximately 5 minutes before participants intends to try to sleep.

    Drug: Placebo

Interventions

  • DrugLemborexant

    Lemborexant 10 mg tablet.

    Also known as: E2006

  • DrugPlacebo

    Placebo tablet matched to lemborexant 10 mg tablet.

06

What researchers measure

Primary outcomes

  1. Change From Baseline of Mean Latency to Persistent Sleep (LPS) Over the Last 2 Nights of 1 Month of Treatment of Lemborexant 10 mg Compared to Placebo

    LPS was defined as the time in minutes from lights off to the first epoch of 20 consecutive epochs of non- wakefulness as measured by polysomnography (PSG). Change from baseline to average LPS on Days 29 and 30 was reported. The outcome measure was planned to be assessed for randomization phase only.

    Time frame: Baseline, Days 29 and 30

Secondary outcomes

  1. Change From Baseline of Mean Objective Sleep Efficiency (SE) Over the Last 2 Nights of 1 Month Treatment of Lemborexant 10 mg Compared to Placebo

    SE was 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 Days 29 and 30 was reported. The outcome measure was planned to be assessed for randomization phase only.

    Time frame: Baseline, Days 29 and 30

  2. Change From Baseline in Mean Objective Wake After Sleep Onset (WASO) Over the Last 2 Nights of 1 Month Treatment of Lemborexant 10 mg Compared to Placebo

    WASO was 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. The outcome measure was planned to be assessed for randomization phase only.

    Time frame: Baseline, Days 29 and 30

  3. Change From Baseline of Subjective Sleep Onset Latency (sSOL) Over the Last 7 Nights of 1 Month Treatment of Lemborexant 10 mg Compared to Placebo

    sSOL was defined as estimated minutes from the time that the participant attempted to sleep until sleep onset. Change from baseline to average sSOL of Nights 24 to 30 was reported. The outcome measure was planned to be assessed for randomization phase only.

    Time frame: Baseline, Nights 24 to 30

  4. Change From Baseline of Subjective Sleep Efficiency (sSE) Over the Last 7 Nights of 1 Month of Treatment of Lemborexant 10 mg Compared to Placebo

    sSE was defined as percentage of subjective total sleep time (sTST) divided by subjective time spent in bed, calculated as the interval from the time the participant reported attempting to sleep until the time participant stopped trying to sleep for the night (operationalized as the time the participant got out of bed for the day), and time spent asleep derived from subjective time spent in bed minus subjective wake after sleep onset (sWASO). WASO: estimated minutes of wake at night after initial sleep onset to time stopped trying to sleep for the night. Change from baseline to average sSE of Nights 24 to 30 was reported. The outcome measure was planned to be assessed for randomization phase only.

    Time frame: Baseline, Nights 24 to 30

  5. Change From Baseline in Subjective Wake After Sleep Onset Over the Last 7 Nights of 1 Month Treatment of Lemborexant 10 mg Compared to Placebo

    sWASO was defined as sum of estimated minutes of wake during the night after initial sleep onset until the time the participant stopped trying to sleep for the night, operationalized as the time the participant got out of bed for the day. Change from baseline to average sWASO of Nights 24 to 30 was reported. The outcome measure was planned to be assessed for randomization phase only.

    Time frame: Baseline, Nights 24 to 30

  6. Change From Baseline of Mean Latency to Persistent Sleep Over the First 2 Nights of 1 Month of Treatment of Lemborexant 10 mg Compared to Placebo

    LPS was defined as the time in minutes from lights off to the first epoch of 20 consecutive epochs of non- wakefulness as measured by polysomnography. Change from baseline to average LPS on Nights 1 and 2 was reported. The outcome measure was planned to be assessed for randomization phase only.

    Time frame: Baseline, Nights 1 and 2

  7. Change From Baseline of Mean Sleep Efficiency Over the First 2 Nights of 1 Month of Treatment of Lemborexant 10 mg Compared to Placebo

    SE was defined as percentage of time spent in bed asleep, calculated as total sleep time divided by interval from lights off until lights on as measured by PSG, multiplied by 100. Change from baseline to average SE on Nights 1 and 2 was reported. The outcome measure was planned to be assessed for randomization phase only.

    Time frame: Baseline, Nights 1 and 2

  8. Change From Baseline of Mean Wake After Sleep Onset Over the First 2 Nights of 1 Month of Treatment of Lemborexant 10 mg Compared to Placebo

    WASO was 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 Nights 1 and 2 was reported. The outcome measure was planned to be assessed for randomization phase only.

    Time frame: Baseline, Nights 1 and 2

  9. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

    A TEAE was defined as an AE with onset date on or after the first dose of study drug up to 14 days after the last dose of study drug. An SAE was any untoward medical occurrence that at any dose: resulted in death, was life-threatening (that is, participant was at immediate risk of death from AE as it occurred; this did not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug). The outcome measure was planned to be assessed for randomization phase only.

    Time frame: From the first dose of study drug up to 44 days

  10. Change From Baseline in Insomnia Severity Index (ISI) Total Score After 1 Month of Treatment With Lemborexant 10 mg Compared to Placebo

    The ISI was a 7-item self-report questionnaire assessing the nature, severity, and impact of insomnia. The 7 dimensions evaluated are 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 is used to rate each item (from 0= no problem, 1= satisfied, 2= moderately satisfied, 3= dissatisfied and 4=very severe problem). Total ISI score was calculated as sum of scores of all 7 individual items, ranging between 0 to 28. A higher score indicated more severe illness. The outcome measure was planned to be assessed for randomization phase only.

    Time frame: Baseline to Day 31

  11. Change From Baseline in Insomnia Severity Index Daytime Functioning Score After 1 Month of Treatment With Lemborexant 10 mg Compared to Placebo

    The ISI is a 7-item self-report questionnaire assessing the nature, severity, and impact of insomnia. The 4 dimensions out of 7 evaluated for daily functioning are severity of: 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 is used to rate each item (from 0= no problem, 1= satisfied, 2= moderately satisfied, 3= dissatisfied and 4=very severe problem), Daytime Functioning score was calculated as sum of scores of item 4 to 7, ranging between 0 to 16. A higher score indicated more severe illness. The outcome measure was planned to be assessed for randomization phase only.

    Time frame: Baseline to Day 31

  12. Number of Participants With Rebound Insomnia on Average of First 3 Nights (Nights 31 to 33), Average of First 7 Nights (Nights 31 to 37), and Average of Last 7 Nights (Nights 38 to 44) During the Follow-up Period

    Rebound insomnia was defined as worsened sleep relative to screening after study drug treatment was completed. Sleep diary data from the follow-up period was compared to sleep diary data from the screening period to assess whether participants experience rebound insomnia. Number of participants with rebound insomnia assessed by sleep diary (sSOL and sWASO) was reported. The outcome measure was planned to be assessed for randomization phase only.

    Time frame: First 3 nights (Nights 31 to 33), First 7 nights (Nights 31 to 37) and Last 7 nights (Nights 38 to 44) of Follow up Period

  13. Change From Baseline in Mean Morning Residual Sleepiness Score Evaluated During Treatment and Follow-up Periods

    The Sleep Diary was used to assess subjective ratings of morning sleepiness with the following question: "How sleepy/alert do you feel this morning?" Participants rated their sleepiness/alertness level on a Likert scale from 1 to 9, with 1 being extremely poor (sleepy) and 9 being extremely good (alert). Higher score indicated better outcome. Change from baseline of the morning sleepiness item on the sleep diary for the average of first 7 mornings and the average of last 7 mornings of the Treatment Period; and the average of the first 7 mornings and the average of the last 7 mornings of the Follow-up Period was reported. The outcome measure was planned to be assessed for randomization phase only.

    Time frame: Baseline, First 7 mornings (Mornings 1 to 7) and Last 7 mornings (Mornings 24 to 30) of Treatment period; First 7 mornings (Mornings 31 to 37) and Last 7 mornings (Mornings 38 to 44) of Follow-up period

07

Results

Posted Dec 20, 2024

Participant flow

Participants took part in the study at 21 sites in China mainland and 2 sites in Taiwan from 06 November 2020 to 17 March 2023.

Prerandomization Phase
Participant flow — Prerandomization Phase
MilestonePrerandomization Phase: All ParticipantsRandomization Phase: PlaceboRandomization Phase: Lemborexant 10 mg
Started19400
Completed19400
Not completed000
Randomization Phase
Participant flow — Randomization Phase
MilestonePrerandomization Phase: All ParticipantsRandomization Phase: PlaceboRandomization Phase: Lemborexant 10 mg
Started010094
Full analysis set (fas)010093
Completed09692
Not completed042
Withdrew: Adverse event001
Withdrew: Other020
Withdrew: Withdrawal by subject021

Outcome measures

PrimaryChange From Baseline of Mean Latency to Persistent Sleep (LPS) Over the Last 2 Nights of 1 Month of Treatment of Lemborexant 10 mg Compared to Placebo

LPS was defined as the time in minutes from lights off to the first epoch of 20 consecutive epochs of non- wakefulness as measured by polysomnography (PSG). Change from baseline to average LPS on Days 29 and 30 was reported. The outcome measure was planned to be assessed for randomization phase only.

Time frame:
Baseline, Days 29 and 30
Reported as:
Mean · minutes
Change From Baseline of Mean Latency to Persistent Sleep (LPS) Over the Last 2 Nights of 1 Month of Treatment of Lemborexant 10 mg Compared to Placebo
minutesRandomization Phase: PlaceboRandomization Phase: Lemborexant 10 mg
Change From Baseline of Mean Latency to Persistent Sleep (LPS) Over the Last 2 Nights of 1 Month of Treatment of Lemborexant 10 mg Compared to Placebo-21.71 ± 42.809-39.47 ± 46.147
Statistical analysis
  • Randomization Phase: Placebo vs Randomization Phase: Lemborexant 10 mg · MMRM · p = 0.0585 (Data was analyzed using mixed effect model repeated measurement analysis (MMRM), and the missing values were imputed using multiple imputation and assumed to be missing not at random (MNAR).) · Ls geometric mean ratio: 0.795 · 95% CI 0.627 to 1.008
SecondaryChange From Baseline of Mean Objective Sleep Efficiency (SE) Over the Last 2 Nights of 1 Month Treatment of Lemborexant 10 mg Compared to Placebo

SE was 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 Days 29 and 30 was reported. The outcome measure was planned to be assessed for randomization phase only.

Time frame:
Baseline, Days 29 and 30
Reported as:
Mean · % time (minutes) in bed asleep
Change From Baseline of Mean Objective Sleep Efficiency (SE) Over the Last 2 Nights of 1 Month Treatment of Lemborexant 10 mg Compared to Placebo
% time (minutes) in bed asleepRandomization Phase: PlaceboRandomization Phase: Lemborexant 10 mg
Change From Baseline of Mean Objective Sleep Efficiency (SE) Over the Last 2 Nights of 1 Month Treatment of Lemborexant 10 mg Compared to Placebo7.40 ± 12.85315.33 ± 11.124
Statistical analysis
  • Randomization Phase: Placebo vs Randomization Phase: Lemborexant 10 mg · MMRM · p = <0.0001 (Data was analyzed using MMRM, and the missing values were imputed using multiple imputation and assumed to be MNAR.) · Lsm difference: 7.10 · 95% CI 4.39 to 9.81
SecondaryChange From Baseline in Mean Objective Wake After Sleep Onset (WASO) Over the Last 2 Nights of 1 Month Treatment of Lemborexant 10 mg Compared to Placebo

WASO was 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. The outcome measure was planned to be assessed for randomization phase only.

Time frame:
Baseline, Days 29 and 30
Reported as:
Mean · minutes
Change From Baseline in Mean Objective Wake After Sleep Onset (WASO) Over the Last 2 Nights of 1 Month Treatment of Lemborexant 10 mg Compared to Placebo
minutesRandomization Phase: PlaceboRandomization Phase: Lemborexant 10 mg
Change From Baseline in Mean Objective Wake After Sleep Onset (WASO) Over the Last 2 Nights of 1 Month Treatment of Lemborexant 10 mg Compared to Placebo-14.30 ± 42.733-36.65 ± 35.342
Statistical analysis
  • Randomization Phase: Placebo vs Randomization Phase: Lemborexant 10 mg · MMRM · p = 0.0002 (Data was analyzed using MMRM, and the missing values were imputed using multiple imputation and assumed to be MNAR.) · Lsm difference: -17.84 · 95% CI -27.16 to -8.51
SecondaryChange From Baseline of Subjective Sleep Onset Latency (sSOL) Over the Last 7 Nights of 1 Month Treatment of Lemborexant 10 mg Compared to Placebo

sSOL was defined as estimated minutes from the time that the participant attempted to sleep until sleep onset. Change from baseline to average sSOL of Nights 24 to 30 was reported. The outcome measure was planned to be assessed for randomization phase only.

Time frame:
Baseline, Nights 24 to 30
Reported as:
Mean · minutes
Change From Baseline of Subjective Sleep Onset Latency (sSOL) Over the Last 7 Nights of 1 Month Treatment of Lemborexant 10 mg Compared to Placebo
minutesRandomization Phase: PlaceboRandomization Phase: Lemborexant 10 mg
Change From Baseline of Subjective Sleep Onset Latency (sSOL) Over the Last 7 Nights of 1 Month Treatment of Lemborexant 10 mg Compared to Placebo-22.41 ± 32.183-33.10 ± 50.060
Statistical analysis
  • Randomization Phase: Placebo vs Randomization Phase: Lemborexant 10 mg · MMRM · p = 0.0063 (Data was analyzed using MMRM, and the missing values were imputed using multiple imputation and assumed to be MNAR.) · Ls geometric mean ratio: 0.776 · 95% CI 0.647 to 0.930
SecondaryChange From Baseline of Subjective Sleep Efficiency (sSE) Over the Last 7 Nights of 1 Month of Treatment of Lemborexant 10 mg Compared to Placebo

sSE was defined as percentage of subjective total sleep time (sTST) divided by subjective time spent in bed, calculated as the interval from the time the participant reported attempting to sleep until the time participant stopped trying to sleep for the night (operationalized as the time the participant got out of bed for the day), and time spent asleep derived from subjective time spent in bed minus subjective wake after sleep onset (sWASO). WASO: estimated minutes of wake at night after initial sleep onset to time stopped trying to sleep for the night. Change from baseline to average sSE of Nights 24 to 30 was reported. The outcome measure was planned to be assessed for randomization phase only.

Time frame:
Baseline, Nights 24 to 30
Reported as:
Mean · % of time (minutes) in bed asleep
Change From Baseline of Subjective Sleep Efficiency (sSE) Over the Last 7 Nights of 1 Month of Treatment of Lemborexant 10 mg Compared to Placebo
% of time (minutes) in bed asleepRandomization Phase: PlaceboRandomization Phase: Lemborexant 10 mg
Change From Baseline of Subjective Sleep Efficiency (sSE) Over the Last 7 Nights of 1 Month of Treatment of Lemborexant 10 mg Compared to Placebo8.88 ± 11.63013.16 ± 16.559
Statistical analysis
  • Randomization Phase: Placebo vs Randomization Phase: Lemborexant 10 mg · MMRM · p = 0.0242 (Data was analyzed using MMRM, and the missing values were imputed using multiple imputation and assumed to be MNAR.) · Lsm difference: 4.49 · 95% CI 0.59 to 8.39
SecondaryChange From Baseline in Subjective Wake After Sleep Onset Over the Last 7 Nights of 1 Month Treatment of Lemborexant 10 mg Compared to Placebo

sWASO was defined as sum of estimated minutes of wake during the night after initial sleep onset until the time the participant stopped trying to sleep for the night, operationalized as the time the participant got out of bed for the day. Change from baseline to average sWASO of Nights 24 to 30 was reported. The outcome measure was planned to be assessed for randomization phase only.

Time frame:
Baseline, Nights 24 to 30
Reported as:
Mean · minutes
Change From Baseline in Subjective Wake After Sleep Onset Over the Last 7 Nights of 1 Month Treatment of Lemborexant 10 mg Compared to Placebo
minutesRandomization Phase: PlaceboRandomization Phase: Lemborexant 10 mg
Change From Baseline in Subjective Wake After Sleep Onset Over the Last 7 Nights of 1 Month Treatment of Lemborexant 10 mg Compared to Placebo-22.39 ± 48.620-32.14 ± 60.110
Statistical analysis
  • Randomization Phase: Placebo vs Randomization Phase: Lemborexant 10 mg · MMRM · p = 0.1625 (Data was analyzed using MMRM, and the missing values were imputed using multiple imputation and assumed to be MNAR.) · Lsm difference: -10.36 · 95% CI -24.95 to 4.22
SecondaryChange From Baseline of Mean Latency to Persistent Sleep Over the First 2 Nights of 1 Month of Treatment of Lemborexant 10 mg Compared to Placebo

LPS was defined as the time in minutes from lights off to the first epoch of 20 consecutive epochs of non- wakefulness as measured by polysomnography. Change from baseline to average LPS on Nights 1 and 2 was reported. The outcome measure was planned to be assessed for randomization phase only.

Time frame:
Baseline, Nights 1 and 2
Reported as:
Mean · minutes
Change From Baseline of Mean Latency to Persistent Sleep Over the First 2 Nights of 1 Month of Treatment of Lemborexant 10 mg Compared to Placebo
minutesRandomization Phase: PlaceboRandomization Phase: Lemborexant 10 mg
Change From Baseline of Mean Latency to Persistent Sleep Over the First 2 Nights of 1 Month of Treatment of Lemborexant 10 mg Compared to Placebo-16.52 ± 42.970-34.64 ± 48.102
Statistical analysis
  • Randomization Phase: Placebo vs Randomization Phase: Lemborexant 10 mg · MMRM · p = 0.0515 (Data was analyzed using MMRM, and the missing values were imputed using multiple imputation and assumed to be MNAR.) · Ls geometric mean ratio: 0.815 · 95% CI 0.663 to 1.001
SecondaryChange From Baseline of Mean Sleep Efficiency Over the First 2 Nights of 1 Month of Treatment of Lemborexant 10 mg Compared to Placebo

SE was defined as percentage of time spent in bed asleep, calculated as total sleep time divided by interval from lights off until lights on as measured by PSG, multiplied by 100. Change from baseline to average SE on Nights 1 and 2 was reported. The outcome measure was planned to be assessed for randomization phase only.

Time frame:
Baseline, Nights 1 and 2
Reported as:
Mean · % of time (minutes) in bed asleep
Change From Baseline of Mean Sleep Efficiency Over the First 2 Nights of 1 Month of Treatment of Lemborexant 10 mg Compared to Placebo
% of time (minutes) in bed asleepRandomization Phase: PlaceboRandomization Phase: Lemborexant 10 mg
Change From Baseline of Mean Sleep Efficiency Over the First 2 Nights of 1 Month of Treatment of Lemborexant 10 mg Compared to Placebo6.99 ± 9.59515.58 ± 11.725
Statistical analysis
  • Randomization Phase: Placebo vs Randomization Phase: Lemborexant 10 mg · MMRM · p = <0.0001 (Data was analyzed using MMRM, and the missing values were imputed using multiple imputation and assumed to be MNAR.) · Lsm difference: 7.74 · 95% CI 5.61 to 9.86
SecondaryChange From Baseline of Mean Wake After Sleep Onset Over the First 2 Nights of 1 Month of Treatment of Lemborexant 10 mg Compared to Placebo

WASO was 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 Nights 1 and 2 was reported. The outcome measure was planned to be assessed for randomization phase only.

Time frame:
Baseline, Nights 1 and 2
Reported as:
Mean · minutes
Change From Baseline of Mean Wake After Sleep Onset Over the First 2 Nights of 1 Month of Treatment of Lemborexant 10 mg Compared to Placebo
minutesRandomization Phase: PlaceboRandomization Phase: Lemborexant 10 mg
Change From Baseline of Mean Wake After Sleep Onset Over the First 2 Nights of 1 Month of Treatment of Lemborexant 10 mg Compared to Placebo-17.99 ± 29.782-42.86 ± 35.970
Statistical analysis
  • Randomization Phase: Placebo vs Randomization Phase: Lemborexant 10 mg · MMRM · p = <0.0001 (Data was analyzed using MMRM, and the missing values were imputed using multiple imputation and assumed to be MNAR.) · Lsm difference: -21.25 · 95% CI -28.15 to -14.35
SecondaryNumber of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

A TEAE was defined as an AE with onset date on or after the first dose of study drug up to 14 days after the last dose of study drug. An SAE was any untoward medical occurrence that at any dose: resulted in death, was life-threatening (that is, participant was at immediate risk of death from AE as it occurred; this did not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug). The outcome measure was planned to be assessed for randomization phase only.

Time frame:
From the first dose of study drug up to 44 days
Reported as:
Count of participants · Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
ParticipantsRandomization Phase: PlaceboRandomization Phase: Lemborexant 10 mg
TEAEs2130
Serious TEAEs10
SecondaryChange From Baseline in Insomnia Severity Index (ISI) Total Score After 1 Month of Treatment With Lemborexant 10 mg Compared to Placebo

The ISI was a 7-item self-report questionnaire assessing the nature, severity, and impact of insomnia. The 7 dimensions evaluated are 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 is used to rate each item (from 0= no problem, 1= satisfied, 2= moderately satisfied, 3= dissatisfied and 4=very severe problem). Total ISI score was calculated as sum of scores of all 7 individual items, ranging between 0 to 28. A higher score indicated more severe illness. The outcome measure was planned to be assessed for randomization phase only.

Time frame:
Baseline to Day 31
Reported as:
Mean · Score on a scale
Change From Baseline in Insomnia Severity Index (ISI) Total Score After 1 Month of Treatment With Lemborexant 10 mg Compared to Placebo
Score on a scaleRandomization Phase: PlaceboRandomization Phase: Lemborexant 10 mg
Change From Baseline in Insomnia Severity Index (ISI) Total Score After 1 Month of Treatment With Lemborexant 10 mg Compared to Placebo-6.48 ± 5.246-9.64 ± 5.528
Statistical analysis
  • Randomization Phase: Placebo vs Randomization Phase: Lemborexant 10 mg · ANCOVA · p = 0.0006 (Based on Analysis of Covariance (ANCOVA) model with factors of age group, site, treatment, and the baseline ISI as a covariate.) · Lsm difference: -2.85 · 95% CI -4.45 to -1.25
SecondaryChange From Baseline in Insomnia Severity Index Daytime Functioning Score After 1 Month of Treatment With Lemborexant 10 mg Compared to Placebo

The ISI is a 7-item self-report questionnaire assessing the nature, severity, and impact of insomnia. The 4 dimensions out of 7 evaluated for daily functioning are severity of: 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 is used to rate each item (from 0= no problem, 1= satisfied, 2= moderately satisfied, 3= dissatisfied and 4=very severe problem), Daytime Functioning score was calculated as sum of scores of item 4 to 7, ranging between 0 to 16. A higher score indicated more severe illness. The outcome measure was planned to be assessed for randomization phase only.

Time frame:
Baseline to Day 31
Reported as:
Mean · Score on a scale
Change From Baseline in Insomnia Severity Index Daytime Functioning Score After 1 Month of Treatment With Lemborexant 10 mg Compared to Placebo
Score on a scaleRandomization Phase: PlaceboRandomization Phase: Lemborexant 10 mg
Change From Baseline in Insomnia Severity Index Daytime Functioning Score After 1 Month of Treatment With Lemborexant 10 mg Compared to Placebo-3.76 ± 3.093-5.77 ± 3.510
Statistical analysis
  • Randomization Phase: Placebo vs Randomization Phase: Lemborexant 10 mg · ANCOVA · p = 0.0005 (Based on ANCOVA model with factors of age group, site, treatment, and the baseline ISI as a covariate.) · Lsm difference: -1.74 · 95% CI -2.70 to -0.78
SecondaryNumber of Participants With Rebound Insomnia on Average of First 3 Nights (Nights 31 to 33), Average of First 7 Nights (Nights 31 to 37), and Average of Last 7 Nights (Nights 38 to 44) During the Follow-up Period

Rebound insomnia was defined as worsened sleep relative to screening after study drug treatment was completed. Sleep diary data from the follow-up period was compared to sleep diary data from the screening period to assess whether participants experience rebound insomnia. Number of participants with rebound insomnia assessed by sleep diary (sSOL and sWASO) was reported. The outcome measure was planned to be assessed for randomization phase only.

Time frame:
First 3 nights (Nights 31 to 33), First 7 nights (Nights 31 to 37) and Last 7 nights (Nights 38 to 44) of Follow up Period
Reported as:
Count of participants · Participants
Number of Participants With Rebound Insomnia on Average of First 3 Nights (Nights 31 to 33), Average of First 7 Nights (Nights 31 to 37), and Average of Last 7 Nights (Nights 38 to 44) During the Follow-up Period
ParticipantsRandomization Phase: PlaceboRandomization Phase: Lemborexant 10 mg
sSOL, Average of First 3 nights of follow-up period57
sSOL, Average of First 7 nights of follow-up period67
sSOL, Average of Last 7 nights of follow-up period911
sWASO, Average of First 3 nights of follow-up period1510
sWASO, Average First 7 nights of follow-up period1312
sWASO, Average of Last 7 nights of follow-up period812
SecondaryChange From Baseline in Mean Morning Residual Sleepiness Score Evaluated During Treatment and Follow-up Periods

The Sleep Diary was used to assess subjective ratings of morning sleepiness with the following question: "How sleepy/alert do you feel this morning?" Participants rated their sleepiness/alertness level on a Likert scale from 1 to 9, with 1 being extremely poor (sleepy) and 9 being extremely good (alert). Higher score indicated better outcome. Change from baseline of the morning sleepiness item on the sleep diary for the average of first 7 mornings and the average of last 7 mornings of the Treatment Period; and the average of the first 7 mornings and the average of the last 7 mornings of the Follow-up Period was reported. The outcome measure was planned to be assessed for randomization phase only.

Time frame:
Baseline, First 7 mornings (Mornings 1 to 7) and Last 7 mornings (Mornings 24 to 30) of Treatment period; First 7 mornings (Mornings 31 to 37) and Last 7 mornings (Mornings 38 to 44) of Follow-up period
Reported as:
Mean · Score on a scale
Change From Baseline in Mean Morning Residual Sleepiness Score Evaluated During Treatment and Follow-up Periods
Score on a scaleRandomization Phase: PlaceboRandomization Phase: Lemborexant 10 mg
First 7 mornings of treatment period0.20 ± 0.9820.59 ± 1.284
Last 7 mornings of treatment period0.75 ± 1.5771.15 ± 1.625
First 7 mornings of follow-up period0.81 ± 1.5081.18 ± 1.534
Last 7 mornings of follow-up period0.91 ± 1.6821.22 ± 1.434
Statistical analysis
  • Randomization Phase: Placebo vs Randomization Phase: Lemborexant 10 mg · MMRM · p = 0.0312 (Data was analyzed using MMRM, and the missing values were imputed using multiple imputation and assumed to be MNAR.) · Lsm difference: 0.34 · 95% CI 0.03 to 0.65First 7 mornings of treatment period
  • Randomization Phase: Placebo vs Randomization Phase: Lemborexant 10 mg · MMRM · p = 0.1460 (Data was analyzed using MMRM, and the missing values were imputed using multiple imputation and assumed to be MNAR.) · Lsm difference: 0.32 · 95% CI -0.11 to 0.76Last 7 mornings of treatment period
  • Randomization Phase: Placebo vs Randomization Phase: Lemborexant 10 mg · MMRM · p = 0.1613 (Data was analyzed using MMRM, and the missing values were imputed using multiple imputation and assumed to be MNAR.) · Lsm difference: 0.29 · 95% CI -0.12 to 0.70First 7 mornings of follow-up period
  • Randomization Phase: Placebo vs Randomization Phase: Lemborexant 10 mg · MMRM · p = 0.2852 (Data was analyzed using MMRM, and the missing values were imputed using multiple imputation and assumed to be MNAR.) · Lsm difference: 0.23 · 95% CI -0.19 to 0.65Last 7 mornings of follow-up period

Adverse events

Collected over From signing of the consent form up to 79 days which include 35 days for prerandomization phase and up to 44 days for randomization phase. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Prerandomization Phase: All Participants0/194 (0%)0/194 (0%)19/194 (9.8%)
Randomization Phase: Placebo0/100 (0%)1/100 (1%)20/100 (20%)
Randomization Phase: Lemborexant 10 mg0/94 (0%)0/94 (0%)30/94 (31.9%)
Most frequent serious events
Most frequent serious events
EventPrerandomization Phase: All ParticipantsRandomization Phase: PlaceboRandomization Phase: Lemborexant 10 mg
Benign ovarian tumourNeoplasms benign, malignant and unspecified (incl cysts and polyps)—1/1000/94
Most frequent other events
Showing 10 of 61
Most frequent other events
EventPrerandomization Phase: All ParticipantsRandomization Phase: PlaceboRandomization Phase: Lemborexant 10 mg
COVID-19Infections and infestations3/1943/1008/94
FatigueGeneral disorders0/1940/1002/94
DizzinessNervous system disorders0/1940/1002/94
ThrombocytopeniaBlood and lymphatic system disorders0/1942/1000/94
HyperlipidaemiaMetabolism and nutrition disorders0/1942/1001/94
AnaemiaBlood and lymphatic system disorders1/1940/1001/94
Atrial tachycardiaCardiac disorders0/1940/1001/94
Supraventricular extrasystolesCardiac disorders0/1940/1001/94
Abdominal painGastrointestinal disorders0/1940/1001/94
ConstipationGastrointestinal disorders0/1940/1001/94

Baseline characteristics

The safety analysis set was the group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose safety assessment.

Age, Customized
Age, Customized(Participants)Randomization Phase: PlaceboRandomization Phase: Lemborexant 10 mgTotal
<55 years old7873151
>=55 - <65 years old141933
>=65 - <75 years old8210
Sex: Female, Male
Sex: Female, Male(Participants)Randomization Phase: PlaceboRandomization Phase: Lemborexant 10 mgTotal
Female7458132
Male263662
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Randomization Phase: PlaceboRandomization Phase: Lemborexant 10 mgTotal
Hispanic or Latino000
Not Hispanic or Latino10094194
Unknown or Not Reported000
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Randomization Phase: PlaceboRandomization Phase: Lemborexant 10 mgTotal
Chinese10094194
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Study locations

23 sites
  • Beijing Tiantan Hosptial, Capital Medical University
    Beijing, Beijing, China
  • Peking University Sixth Hospital
    Beijing, Beijing, China
  • Xuanwu Hospital Capital Medical University
    Beijing, Beijing, China
  • Guangdong Provincial People's Hospital
    Guangzhou, Guangdong, China
  • Nanfang Hospital of Southern Medical University
    Guangzhou, Guangdong, China
  • The First Affiliated Hospital of Jinan University
    Guangzhou, Guangdong, China
  • The First Hospital of Hebei Medical University
    Shijiazhuang, Hebei, China
  • The Third Hospital of Hebei Medical University
    Shijiazhuang, Hebei, China
  • Henan Mental Health Center
    Xinxiang, Henan, China
  • Wuhan Mental Health Center
    Wuhan, Hubei, China
  • Nanjing Brain Hosptial
    Nanjing, Jiangsu, China
  • The Second Affiliated Hospital of Soochow University
    Suzhou, Jiangsu, China
  • The Second Affiliated Hospital of Nanchang University
    Nanchang, Jiangxi, China
  • Jilin First University Affiliated Hospital
    Changchun, Jilin, China
  • Inner Mongolia Autonomous Region Peoples Hospital
    Hohhot, Mongolia, China
  • Tangdu Hospital
    Xian, Shaanxi, China
  • Shandong Provincial Qianfushan Hospital
    Jinan, Shandong, China
  • Huashan Hospital Fudan University
    Shanghai, Shanghai, China
  • Shanghai Mental Health Center
    Shanghai, Shanghai, China
  • First Hospital of Shanxi Medical University
    Taiyuan, Shannxi, China
  • Tianjin Anding Hospital
    Tianjin, Tianjin, China
  • Chang Gung Medical Foundation Linkou Chang Gung Memorial Hospital
    Taoyuan, Taipei, Taiwan
  • Taipei Veterans General Hospital
    Taipei, Taiwan
09

References and documents

Study documents

  • Study protocol · Jun 28, 2022
  • Statistical analysis plan · Sep 29, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 20, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04549168
Lead sponsor
Eisai Co., Ltd.
Responsible party
Sponsor
First posted
Sep 16, 2020
Start date
Nov 6, 2020
Primary completion
Mar 17, 2023
Completion
Mar 17, 2023
Results posted
Dec 20, 2024
Last update
Dec 20, 2024

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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