CompletedNCT02350309Updated Jan 18, 2020Results posted

Study to Evaluate the Effect of 2 Dosage Strengths of Lemborexant (E2006) on a Multiple Sleep Latency Test in Participants With Insomnia Disorder

A Phase 1 interventional study of Lemborexant 5 mg and Lemborexant 10 mg in Insomnia Disorder, sponsored by Eisai Inc.. Completed at 2 sites in United States. Open to participants aged 18 Years to 99 Years. Per ClinicalTrials.gov, last updated 2020-01-18.

Sponsored by Eisai Inc. · Phase 1, Interventional, and Treatment

Phase: Phase 1
Study type: Interventional
Enrollment: 69
Allocation: Randomized
Ages: 18 Years to 99 Years
Sex: All

Study summary

This is a single-dose, randomized, placebo-controlled, 3-way crossover study of 2 dosage strengths of lemborexant (5 mg and 10 mg) in participants with insomnia disorder.

Read the detailed description

The study will have 2 phases: Prerandomization and Randomization. The Prerandomization Phase will consist of 2 periods that taken together, will last up to a maximum of 21 days: a Screening Period and a Baseline Period. The Randomization Phase will comprise 4 treatment periods (Treatment 1, Treatment 2, Treatment 3, Treatment 4) with intervening washout periods between treatment periods (Washout 1, Washout 2, Washout 3). A single dose of study drug will be administered in a randomized, 3-way double-blind crossover manner at Treatment Periods 1-3; flurazepam 30 mg will be administered in an open-label manner at Treatment Period 4.

Conditions studied

Insomnia Disorder

Browse trials for

Sleep Initiation and Maintenance Disorders 1,856

Keywords

Insomnia Disorder
E2006
Multiple Sleep Latency Test
Lemborexant

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 69 is close to 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 Inc. is the lead sponsor of 360 studies on the registry; 7 are open to participants now.

Of its 81 completed or terminated interventional studies of FDA-regulated products, 54 (67%) have results posted.

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

Who can participate

Ages eligible: 18 Years to 99 Years
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Male or female, age 18 or older, at the time of informed consent.
Meets the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for Insomnia Disorder, as follows:
1. Complains of dissatisfaction with nighttime sleep despite adequate opportunity for sleep, with complaint being one or more of the following: difficulty getting to sleep, difficulty staying asleep, or awakening earlier in the morning than desired.
2. Frequency of complaint greater than or equal to 3 times per week.
3. Duration of complaint greater than or equal to 3 months.
4. Associated with complaint of daytime impairment.
Insomnia Severity Index score greater than or equal to 15 at Screening.
Regular time in bed between 7 and 9 hours as reported at Screening.
Regular bedtime, defined as the time the participant attempts to fall asleep, between 21:00 and 24:00 and regular wake time between 05:00 and 09:00 as reported at Screening.
Confirmation of current insomnia symptoms as determined from responses on the Sleep Diary completed for 7 nights during Screening, such that participant Sleep Onset Latency (sSOL) greater than or equal to 30 minutes on at least 3 nights and subjective Wake After Sleep Onset (sWASO) greater than or equal to 60 minutes on at least 3 nights.

Exclusion criteria

Exclusion Criteria:

Excessive morning sleepiness at Baseline as determined by average SOL at Baseline less than 10 minutes.
Females must not be lactating or pregnant at Screening or Baseline (documented by a negative beta-human chorionic gonadotropin [beta-hCG] or human chorionic gonadotropin [hCG] test with a minimum sensitivity of 25 IU/L or equivalent units of beta-hCG or hCG). (Note: A negative urine pregnancy test is required at check-in before each dose of study drug and flurazepam).
If females of childbearing potential:
1. Had unprotected sexual intercourse within 30 days before study entry and do not agree to use a highly effective method of contraception (eg, total abstinence, an intrauterine device, a double-barrier method [such as condom plus diaphragm with spermicide], a contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia) throughout the entire study period or for 28 days after study drug discontinuation.
2. Are currently abstinent, and do not agree to use a double barrier method (as described above) or refrain from sexual activity during the study period or for 28 days after study drug discontinuation.
3. Are using hormonal contraceptives but are not on a stable dose of the same hormonal contraceptive product for at least 4 weeks before dosing and do not agree to use the same contraceptive during the study or for 28 days after study drug discontinuation.
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 (ie, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing).
A current diagnosis of sleep-related breathing disorder, 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.
Reports experiencing within the past year confusional arousals, symptoms of REM Behavior Disorder, or sleep-related violent behavior on Munich Parasomnia Scale (MUPS), or a history of aberrant nocturnal behaviors including sleep-driving or sleep-eating.
Habitually naps more than 3 times per week.
History of drug or alcohol dependency or abuse within approximately the last 2 years.
Has a positive drug screen at Screening.
A prolonged QT/QTc interval (QTc greater than 450 ms) as demonstrated by a repeated ECG at Screening (repeated only if initial ECG indicates a QTc interval greater than 450 ms).
Any suicidal ideation with intent with or without a plan at Screening or within 6 months of Screening or any lifetime suicidal behavior.
Evidence of clinically significant disease (eg, cardiac, respiratory, gastrointestinal, renal, psychiatric or neurological disease, or chronic pain) that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments.
Used any prohibited prescription or over-the-counter concomitant medications within 2 weeks prior to Screening, or between Screening and Randomization.
Used any modality of treatment for insomnia, including cognitive behavioral therapy or marijuana within 2 weeks prior to Screening, or between Screening and Randomization.
Scheduled for surgery during the study.
Transmeridian travel across more than 3 time zones in the 2 weeks before Screening, or between Screening and Baseline, or plans to travel more than 3 times zones during the study.
Hypersensitivity to flurazepam, the study drug, or any of the excipients.
Currently enrolled in another clinical trial or used any investigational drug or device within 28 days or 5 x the half-life, whichever is longer preceding informed consent.

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover assignment
Masking: Double (Participant, Investigator)
Enrollment: 69 participants (actual)

Study arms

Experimental
Lemborexant 5 mg
Participants will receive a single, oral tablet formulation dose of lemborexant 5 mg within 5 minutes before bedtime.
Drug: Lemborexant 5 mg
Experimental
Lemborexant 10 mg
Participants will receive a single, oral tablet formulation dose of lemborexant 10 mg within 5 minutes before bedtime.
Drug: Lemborexant 10 mg
Placebo comparator
Lemborexant-matched Placebo
Participants will receive a single, oral tablet formulation dose of lemborexant-matched placebo within 5 minutes before bedtime.
Drug: Lemborexant-matched placebo.
Active comparator
Flurazepam 30 mg
Participants will receive a single, oral capsule formulation dose of flurazepam 30 mg within 5 minutes before bedtime.
Drug: Flurazepam 30 mg

Interventions

DrugLemborexant 5 mg
Lemborexant 5 mg tablet.
Also known as: E2006
DrugLemborexant 10 mg
Lemborexant 10 mg tablet.
Also known as: E2006
DrugLemborexant-matched placebo.
Lemborexant-matched placebo tablet.
Also known as: E2006
DrugFlurazepam 30 mg
Flurazepam 30 mg capsule.

What researchers measure

Primary outcomes

Mean Change From Baseline in the Average Sleep Onset Latency (SOL) From Modified-Multiple Sleep Latency Test (M-MSLT) for Each Treatment in Treatment Periods 1 to 3
SOL is defined as the length of time that it takes to accomplish the transition from full wakefulness to sleep. The multiple sleep latency test (MSLT) is a widely used method for objectively quantifying excessive, pathological, or pharmacologically induced residual sleepiness by measuring the number of minutes that it takes a participant to fall asleep. The MSLT was modified to include four Sleep Latency Tests (SLTs), with the first starting at 45 minutes after morning wake time, and the subsequent three occurring at 30-minute intervals for a total of 4 SLT's per M-MSLT. Each SLT was scored to determine the latency in minutes (with precision to 0.5 minute) from lights off to sleep onset; trials during which sleep onset did not occur were assigned a latency of 20 minutes. The four SLTs for each participant were averaged to obtain the mean SOL.
Time frame: Baseline, Day 2 of each of three treatment periods that were separated by approximately 2 weeks (for a total of up to 4 weeks)

Secondary outcomes

Number of Participants With an Average SOL of Less Than (<) 8.0 Minutes for Each Treatment
SOL is defined as the length of time that it takes to accomplish the transition from full wakefulness to sleep. The MSLT is a widely used method for objectively quantifying excessive, pathological, or pharmacologically induced residual sleepiness by measuring the number of minutes that it takes a participant to fall asleep. The MSLT was modified to include four SLTs, with the first starting at 45 minutes after morning wake time, and the subsequent three occurring at 30-minute intervals for a total of 4 SLT's per M-MSLT. Each SLT was scored to determine the latency in minutes (with precision to 0.5 minute) from lights off to sleep onset; trials during which sleep onset did not occur were assigned a latency of 20 minutes. The four SLTs for each participant were averaged to obtain the mean SOL.
Time frame: Day 2 of each of three treatment periods that were separated by approximately 2 weeks (for a total of up to 6 weeks)
Number of Participants Whose Treatment Difference (Under Either Dose of Lemborexant) Average SOL Score is More Than (>) 6.0 Minutes Shorter Than Placebo
SOL is defined as the length of time that it takes to accomplish the transition from full wakefulness to sleep. The MSLT is a widely used method for objectively quantifying excessive, pathological, or pharmacologically induced residual sleepiness by measuring the number of minutes that it takes a participant to fall asleep. The MSLT was modified to include four SLTs, with the first starting at 45 minutes after morning wake time, and the subsequent three occurring at 30-minute intervals for a total of 4 SLT's per M-MSLT. Each SLT was scored to determine the latency in minutes (with precision to 0.5 minute) from lights off to sleep onset; trials during which sleep onset did not occur were assigned a latency of 20 minutes. The four SLTs for each participant were averaged to obtain the mean SOL.
Time frame: Day 2 of each of three treatment periods that are separated by approximately 2 weeks (for a total of up to 6 weeks)
Number of Participants Whose Average SOL is <8.0 Minutes and >6.0 Minutes Shorter Than Placebo
SOL is defined as the length of time that it takes to accomplish the transition from full wakefulness to sleep. The MSLT is a widely used method for objectively quantifying excessive, pathological, or pharmacologically induced residual sleepiness by measuring the number of minutes that it takes a participant to fall asleep. The MSLT was modified to include four SLTs, with the first starting at 45 minutes after morning wake time, and the subsequent three occurring at 30-minute intervals for a total of 4 SLT's per M-MSLT. Each SLT was scored to determine the latency in minutes (with precision to 0.5 minute) from lights off to sleep onset; trials during which sleep onset did not occur were assigned a latency of 20 minutes. The four SLTs for each participant were averaged to obtain the mean SOL.
Time frame: Day 2 of each of three treatment periods that are separated by approximately 2 weeks (for a total of up to 6 weeks)
Mean Change From Baseline in the Average SOL From the M-MSLT in Treatment Period 4
SOL is defined as the length of time that it takes to accomplish the transition from full wakefulness to sleep. The MSLT is a widely used method for objectively quantifying excessive, pathological, or pharmacologically induced residual sleepiness by measuring the number of minutes that it takes a participant to fall asleep. The MSLT was modified to include four SLTs, with the first starting at 45 minutes after morning wake time, and the subsequent three occurring at 30-minute intervals for a total of 4 SLT's per M-MSLT. Each SLT was scored to determine the latency in minutes (with precision to 0.5 minute) from lights off to sleep onset; trials during which sleep onset did not occur were assigned a latency of 20 minutes. The four SLTs for each participant were averaged to obtain the mean SOL.
Time frame: Baseline, Day 2 of Treatment Period 4 (Week 6)
Mean Plasma Concentrations of Lemborexant and Metabolite M10 in the Morning Following M-MSLT
The MSLT is a widely used method for objectively quantifying excessive, pathological, or pharmacologically induced residual sleepiness by measuring the number of minutes that it takes a participant to fall asleep. The MSLT was modified to include four SLTs, with the first starting at 45 minutes after morning wake time, and the subsequent three occurring at 30-minute intervals for a total of 4 SLT's per M-MSLT.
Time frame: Days 2, 16 and 30 within 20 minutes after the end of 4th SLT (up to 155 minutes after wake time)
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) That Led to Death and Study Drug Discontinuation
Time frame: From first dose of study drug up to Day 54
Number of Participants With Clinically Significant Abnormal Laboratory Values
Time frame: From first dose of study drug up to Day 54
Number of Participants With Clinically Significant Change From Baseline in Vital Signs Values
Time frame: From first dose of study drug up to Day 54
Number of Participants With Clinically Significant Shifts From Baseline in Electrocardiogram (ECG) Parameters
Time frame: From first dose of study drug up to Day 54
Relationship Between PK Concentrations of Lemborexant and Sleepiness as Measured by M-MSLT
Pearson correlation was used to calculate the relationship between PK concentration of lemborexant and sleepiness. The M-MSLT is a widely used method for objectively quantifying excessive, pathological, or pharmacologically induced residual sleepiness by measuring the number of minutes that it takes a participant to fall asleep. The MSLT was modified to include four SLTs, with the first starting at 45 minutes after morning wake time, and the subsequent three occurring at 30-minute intervals for a total of 4 SLT's per M-MSLT. Each SLT was scored to determine the latency in minutes (with precision to 0.5 minute) from lights off to sleep onset; trials during which sleep onset did not occur were assigned a latency of 20 minutes.
Time frame: Baseline up to Day 44 (Week 6)

Results

Posted Jan 18, 2020

Participant flow

Participants took part in the study at 2 investigative sites in the United Sates from 13 December 2014 to 21 April 2015.

Treatment Period 1 (2 Days)

Participant flow — Treatment Period 1 (2 Days)
Milestone	Placebo, Lemborexant 5 mg, Lemborexant 10 mg, Flurazepam 30 mg	Lemborexant 10 mg, Placebo, Lemborexant 5 mg, Flurazepam 30 mg	Lemborexant 5 mg, Lemborexant 10 mg, Placebo, Flurazepam 30 mg	Lemborexant 10 mg, Lemborexant 5 mg, Placebo, Flurazepam 30 mg	Lemborexant 5 mg, Placebo, Lemborexant 10 mg, Flurazepam 30 mg	Placebo, Lemborexant 10 mg, Lemborexant 5 mg, Flurazepam 30 mg
Started	12	11	11	11	12	12
Completed	12	11	10	11	12	12
Not completed	0	0	1	0	0	0
Withdrew: Physician decision	0	0	1	0	0	0

Washout Period 1 (12-16 Days)

Participant flow — Washout Period 1 (12-16 Days)
Milestone	Placebo, Lemborexant 5 mg, Lemborexant 10 mg, Flurazepam 30 mg	Lemborexant 10 mg, Placebo, Lemborexant 5 mg, Flurazepam 30 mg	Lemborexant 5 mg, Lemborexant 10 mg, Placebo, Flurazepam 30 mg	Lemborexant 10 mg, Lemborexant 5 mg, Placebo, Flurazepam 30 mg	Lemborexant 5 mg, Placebo, Lemborexant 10 mg, Flurazepam 30 mg	Placebo, Lemborexant 10 mg, Lemborexant 5 mg, Flurazepam 30 mg
Started	12	11	10	11	12	12
Completed	12	11	10	11	12	12
Not completed	0	0	0	0	0	0

Treatment Period 2 (2 Days)

Participant flow — Treatment Period 2 (2 Days)
Milestone	Placebo, Lemborexant 5 mg, Lemborexant 10 mg, Flurazepam 30 mg	Lemborexant 10 mg, Placebo, Lemborexant 5 mg, Flurazepam 30 mg	Lemborexant 5 mg, Lemborexant 10 mg, Placebo, Flurazepam 30 mg	Lemborexant 10 mg, Lemborexant 5 mg, Placebo, Flurazepam 30 mg	Lemborexant 5 mg, Placebo, Lemborexant 10 mg, Flurazepam 30 mg	Placebo, Lemborexant 10 mg, Lemborexant 5 mg, Flurazepam 30 mg
Started	12	11	10	11	12	12
Completed	12	11	10	11	12	12
Not completed	0	0	0	0	0	0

Washout Period 2 (12-16 Days)

Participant flow — Washout Period 2 (12-16 Days)
Milestone	Placebo, Lemborexant 5 mg, Lemborexant 10 mg, Flurazepam 30 mg	Lemborexant 10 mg, Placebo, Lemborexant 5 mg, Flurazepam 30 mg	Lemborexant 5 mg, Lemborexant 10 mg, Placebo, Flurazepam 30 mg	Lemborexant 10 mg, Lemborexant 5 mg, Placebo, Flurazepam 30 mg	Lemborexant 5 mg, Placebo, Lemborexant 10 mg, Flurazepam 30 mg	Placebo, Lemborexant 10 mg, Lemborexant 5 mg, Flurazepam 30 mg
Started	12	11	10	11	12	12
Completed	12	11	10	11	12	12
Not completed	0	0	0	0	0	0

Treatment Period 3 (2 Days)

Participant flow — Treatment Period 3 (2 Days)
Milestone	Placebo, Lemborexant 5 mg, Lemborexant 10 mg, Flurazepam 30 mg	Lemborexant 10 mg, Placebo, Lemborexant 5 mg, Flurazepam 30 mg	Lemborexant 5 mg, Lemborexant 10 mg, Placebo, Flurazepam 30 mg	Lemborexant 10 mg, Lemborexant 5 mg, Placebo, Flurazepam 30 mg	Lemborexant 5 mg, Placebo, Lemborexant 10 mg, Flurazepam 30 mg	Placebo, Lemborexant 10 mg, Lemborexant 5 mg, Flurazepam 30 mg
Started	12	11	10	11	12	12
Completed	12	11	10	11	12	12
Not completed	0	0	0	0	0	0

Washout Period 3 (12-16 Days)

Participant flow — Washout Period 3 (12-16 Days)
Milestone	Placebo, Lemborexant 5 mg, Lemborexant 10 mg, Flurazepam 30 mg	Lemborexant 10 mg, Placebo, Lemborexant 5 mg, Flurazepam 30 mg	Lemborexant 5 mg, Lemborexant 10 mg, Placebo, Flurazepam 30 mg	Lemborexant 10 mg, Lemborexant 5 mg, Placebo, Flurazepam 30 mg	Lemborexant 5 mg, Placebo, Lemborexant 10 mg, Flurazepam 30 mg	Placebo, Lemborexant 10 mg, Lemborexant 5 mg, Flurazepam 30 mg
Started	12	11	10	11	12	12
Completed	12	11	10	11	12	12
Not completed	0	0	0	0	0	0

Treatment Period 4 (2 Days)

Participant flow — Treatment Period 4 (2 Days)
Milestone	Placebo, Lemborexant 5 mg, Lemborexant 10 mg, Flurazepam 30 mg	Lemborexant 10 mg, Placebo, Lemborexant 5 mg, Flurazepam 30 mg	Lemborexant 5 mg, Lemborexant 10 mg, Placebo, Flurazepam 30 mg	Lemborexant 10 mg, Lemborexant 5 mg, Placebo, Flurazepam 30 mg	Lemborexant 5 mg, Placebo, Lemborexant 10 mg, Flurazepam 30 mg	Placebo, Lemborexant 10 mg, Lemborexant 5 mg, Flurazepam 30 mg
Started	12	11	10	11	12	12
Completed	12	11	10	11	12	11
Not completed	0	0	0	0	0	1
Withdrew: Death in the family	0	0	0	0	0	1

Outcome measures

PrimaryMean Change From Baseline in the Average Sleep Onset Latency (SOL) From Modified-Multiple Sleep Latency Test (M-MSLT) for Each Treatment in Treatment Periods 1 to 3

SOL is defined as the length of time that it takes to accomplish the transition from full wakefulness to sleep. The multiple sleep latency test (MSLT) is a widely used method for objectively quantifying excessive, pathological, or pharmacologically induced residual sleepiness by measuring the number of minutes that it takes a participant to fall asleep. The MSLT was modified to include four Sleep Latency Tests (SLTs), with the first starting at 45 minutes after morning wake time, and the subsequent three occurring at 30-minute intervals for a total of 4 SLT's per M-MSLT. Each SLT was scored to determine the latency in minutes (with precision to 0.5 minute) from lights off to sleep onset; trials during which sleep onset did not occur were assigned a latency of 20 minutes. The four SLTs for each participant were averaged to obtain the mean SOL.

Time frame:: Baseline, Day 2 of each of three treatment periods that were separated by approximately 2 weeks (for a total of up to 4 weeks)
Reported as:: Mean · minutes

Mean Change From Baseline in the Average Sleep Onset Latency (SOL) From Modified-Multiple Sleep Latency Test (M-MSLT) for Each Treatment in Treatment Periods 1 to 3
minutes	Lemborexant-matched Placebo	Lemborexant 5 mg	Lemborexant 10 mg
Baseline	18.25 ± 2.621	18.28 ± 2.61	18.25 ± 2.621
Change at Day 2 After Each Treatment	-3.43 ± 4.424	-4.56 ± 4.693	-6.95 ± 4.967

Statistical analysis

Lemborexant-matched Placebo vs Lemborexant 5 mg · Mixed Models Analysis · p = 0.0262 (The mixed model included treatment, period and sequence as fixed effects, baseline (predose) measurement as a covariate, and participant nested within treatment sequence as a random effect.) · Mean difference (final values): -1.15
Lemborexant-matched Placebo vs Lemborexant 10 mg · Mixed Models Analysis · p = <0.0001 (The mixed model included treatment, period and sequence as fixed effects, baseline (predose) measurement as a covariate, and participant nested within treatment sequence as a random effect.) · Mean difference (final values): -3.48

SecondaryNumber of Participants With an Average SOL of Less Than (<) 8.0 Minutes for Each Treatment

SOL is defined as the length of time that it takes to accomplish the transition from full wakefulness to sleep. The MSLT is a widely used method for objectively quantifying excessive, pathological, or pharmacologically induced residual sleepiness by measuring the number of minutes that it takes a participant to fall asleep. The MSLT was modified to include four SLTs, with the first starting at 45 minutes after morning wake time, and the subsequent three occurring at 30-minute intervals for a total of 4 SLT's per M-MSLT. Each SLT was scored to determine the latency in minutes (with precision to 0.5 minute) from lights off to sleep onset; trials during which sleep onset did not occur were assigned a latency of 20 minutes. The four SLTs for each participant were averaged to obtain the mean SOL.

Time frame:: Day 2 of each of three treatment periods that were separated by approximately 2 weeks (for a total of up to 6 weeks)
Reported as:: Count of participants · Participants

Number of Participants With an Average SOL of Less Than (<) 8.0 Minutes for Each Treatment
Participants	Lemborexant-matched Placebo	Lemborexant 5 mg	Lemborexant 10 mg	Flurazepam 30 mg
Number of Participants With an Average SOL of Less Than (<) 8.0 Minutes for Each Treatment	3	11	20	36

Statistical analysis

Lemborexant-matched Placebo vs Lemborexant 5 mg · McNemar · p = 0.0215 (P-value was calculated based on non-missing two-way contingency table between placebo and study treatment.)
Lemborexant-matched Placebo vs Lemborexant 10 mg · McNemar · p = <0.0001 (P-value was calculated based on non-missing two-way contingency table between placebo and study treatment.)
Lemborexant-matched Placebo vs Flurazepam 30 mg · McNemar · p = <0.0001 (P-value was calculated based on non-missing two-way contingency table between placebo and study treatment.)

SecondaryNumber of Participants Whose Treatment Difference (Under Either Dose of Lemborexant) Average SOL Score is More Than (>) 6.0 Minutes Shorter Than Placebo

Time frame:: Day 2 of each of three treatment periods that are separated by approximately 2 weeks (for a total of up to 6 weeks)
Reported as:: Count of participants · Participants

Number of Participants Whose Treatment Difference (Under Either Dose of Lemborexant) Average SOL Score is More Than (>) 6.0 Minutes Shorter Than Placebo
Participants	Lemborexant 5 mg	Lemborexant 10 mg	Flurazepam 30 mg
Number of Participants Whose Treatment Difference (Under Either Dose of Lemborexant) Average SOL Score is More Than (>) 6.0 Minutes Shorter Than Placebo	9	20	35

SecondaryNumber of Participants Whose Average SOL is <8.0 Minutes and >6.0 Minutes Shorter Than Placebo

Time frame:: Day 2 of each of three treatment periods that are separated by approximately 2 weeks (for a total of up to 6 weeks)
Reported as:: Count of participants · Participants

Number of Participants Whose Average SOL is <8.0 Minutes and >6.0 Minutes Shorter Than Placebo
Participants	Lemborexant 5 mg	Lemborexant 10 mg	Flurazepam 30 mg
Number of Participants Whose Average SOL is <8.0 Minutes and >6.0 Minutes Shorter Than Placebo	4	13	25

SecondaryMean Change From Baseline in the Average SOL From the M-MSLT in Treatment Period 4

Time frame:: Baseline, Day 2 of Treatment Period 4 (Week 6)
Reported as:: Mean · minutes

Mean Change From Baseline in the Average SOL From the M-MSLT in Treatment Period 4
minutes	Flurazepam 30 mg
Baseline	18.25 ± 2.621
Change at Day 2 of Treatment Period 4	-9.49 ± 5.413

SecondaryMean Plasma Concentrations of Lemborexant and Metabolite M10 in the Morning Following M-MSLT

The MSLT is a widely used method for objectively quantifying excessive, pathological, or pharmacologically induced residual sleepiness by measuring the number of minutes that it takes a participant to fall asleep. The MSLT was modified to include four SLTs, with the first starting at 45 minutes after morning wake time, and the subsequent three occurring at 30-minute intervals for a total of 4 SLT's per M-MSLT.

Time frame:: Days 2, 16 and 30 within 20 minutes after the end of 4th SLT (up to 155 minutes after wake time)
Reported as:: Mean · nanogram per milliliter (ng/mL)

Mean Plasma Concentrations of Lemborexant and Metabolite M10 in the Morning Following M-MSLT
nanogram per milliliter (ng/mL)	Lemborexant 5 mg	Lemborexant 10 mg
Lemborexant: Day 2	2.285 ± 1.426	6.423 ± 3.262
Metabolite M10: Day 2	1.246 ± 0.792	2.582 ± 0.959
Lemborexant: Day 16	3.236 ± 1.895	5.306 ± 3.175
Metabolite M10: Day 16	1.361 ± 0.634	2.689 ± 1.592
Lemborexant: Day 30	2.020 ± 1.446	5.293 ± 4.293
Metabolite M10: Day 30	0.994 ± 0.639	2.304 ± 1.534

SecondaryNumber of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) That Led to Death and Study Drug Discontinuation

Time frame:: From first dose of study drug up to Day 54
Reported as:: Count of participants · Participants

Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) That Led to Death and Study Drug Discontinuation
Participants	Lemborexant-matched Placebo	Lemborexant 5 mg	Lemborexant 10 mg	Flurazepam 30 mg
TEAEs	2	5	8	5
SAEs	0	0	0	0
AEs Leading to Death	0	0	0	0
AEs Leading to Discontinuation	0	0	0	0

SecondaryNumber of Participants With Clinically Significant Abnormal Laboratory Values

Time frame:: From first dose of study drug up to Day 54
Reported as:: Count of participants · Participants

Number of Participants With Clinically Significant Abnormal Laboratory Values
Participants	Lemborexant-matched Placebo	Lemborexant 5 mg	Lemborexant 10 mg	Flurazepam 30 mg
Number of Participants With Clinically Significant Abnormal Laboratory Values	0	0	0	0

SecondaryNumber of Participants With Clinically Significant Change From Baseline in Vital Signs Values

Time frame:: From first dose of study drug up to Day 54
Reported as:: Count of participants · Participants

Number of Participants With Clinically Significant Change From Baseline in Vital Signs Values
Participants	Lemborexant-matched Placebo	Lemborexant 5 mg	Lemborexant 10 mg	Flurazepam 30 mg
Number of Participants With Clinically Significant Change From Baseline in Vital Signs Values	0	0	0	0

SecondaryNumber of Participants With Clinically Significant Shifts From Baseline in Electrocardiogram (ECG) Parameters

Time frame:: From first dose of study drug up to Day 54
Reported as:: Count of participants · Participants

Number of Participants With Clinically Significant Shifts From Baseline in Electrocardiogram (ECG) Parameters
Participants	Lemborexant-matched Placebo	Lemborexant 5 mg	Lemborexant 10 mg	Flurazepam 30 mg
Number of Participants With Clinically Significant Shifts From Baseline in Electrocardiogram (ECG) Parameters	0	0	0	0

SecondaryRelationship Between PK Concentrations of Lemborexant and Sleepiness as Measured by M-MSLT

Pearson correlation was used to calculate the relationship between PK concentration of lemborexant and sleepiness. The M-MSLT is a widely used method for objectively quantifying excessive, pathological, or pharmacologically induced residual sleepiness by measuring the number of minutes that it takes a participant to fall asleep. The MSLT was modified to include four SLTs, with the first starting at 45 minutes after morning wake time, and the subsequent three occurring at 30-minute intervals for a total of 4 SLT's per M-MSLT. Each SLT was scored to determine the latency in minutes (with precision to 0.5 minute) from lights off to sleep onset; trials during which sleep onset did not occur were assigned a latency of 20 minutes.

Time frame:: Baseline up to Day 44 (Week 6)
Reported as:: Number · correlation coefficient

Relationship Between PK Concentrations of Lemborexant and Sleepiness as Measured by M-MSLT
correlation coefficient	Lemborexant 5 or 10 mg: All Participants
Relationship Between PK Concentrations of Lemborexant and Sleepiness as Measured by M-MSLT	-0.2746

Adverse events

Collected over From date of first dose of study drug up to Day 54. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Lemborexant-matched Placebo	0/68 (0%)	0/68 (0%)	2/68 (2.9%)
Lemborexant 5 mg	0/69 (0%)	0/69 (0%)	5/69 (7.2%)
Lemborexant 10 mg	0/68 (0%)	0/68 (0%)	8/68 (11.8%)
Flurazepam 30 mg	0/68 (0%)	0/68 (0%)	5/68 (7.4%)

Most frequent other events

Showing 10 of 11

Most frequent other events
Event	Lemborexant-matched Placebo	Lemborexant 5 mg	Lemborexant 10 mg	Flurazepam 30 mg
SomnolenceNervous system disorders	0/68	1/69	3/68	2/68
GastroenteritisInfections and infestations	2/68	0/69	1/68	0/68
Dry mouthGastrointestinal disorders	0/68	0/69	1/68	0/68
DyspepsiaGastrointestinal disorders	0/68	0/69	1/68	0/68
NauseaGastrointestinal disorders	0/68	0/69	1/68	0/68
Upper respiratory tract infectionInfections and infestations	0/68	0/69	1/68	1/68
DysgeusiaNervous system disorders	0/68	0/69	0/68	1/68
HeadacheNervous system disorders	0/68	1/69	0/68	1/68
DiarrhoeaGastrointestinal disorders	0/68	1/69	0/68	0/68
AnxietyPsychiatric disorders	0/68	1/69	0/68	0/68

Baseline characteristics

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

Age, Continuous
Age, Continuous(years)	Placebo, Lemborexant 5 mg, Lemborexant 10 mg, Flurazepam 30 mg	Lemborexant 10 mg, Placebo, Lemborexant 5 mg, Flurazepam 30 mg	Lemborexant 5 mg, Lemborexant 10 mg, Placebo, Flurazepam 30 mg	Lemborexant 10 mg, Lemborexant 5 mg, Placebo, Flurazepam 30 mg	Lemborexant 5 mg, Placebo, Lemborexant 10 mg, Flurazepam 30 mg	Placebo, Lemborexant 10 mg, Lemborexant 5 mg, Flurazepam 30 mg	Total
Mean	49.5 ± 15.73	50.2 ± 12.54	49.0 ± 12.32	52.5 ± 15.91	48.1 ± 13.90	52.2 ± 7.86	50.2 ± 12.91

Sex: Female, Male
Sex: Female, Male(Participants)	Placebo, Lemborexant 5 mg, Lemborexant 10 mg, Flurazepam 30 mg	Lemborexant 10 mg, Placebo, Lemborexant 5 mg, Flurazepam 30 mg	Lemborexant 5 mg, Lemborexant 10 mg, Placebo, Flurazepam 30 mg	Lemborexant 10 mg, Lemborexant 5 mg, Placebo, Flurazepam 30 mg	Lemborexant 5 mg, Placebo, Lemborexant 10 mg, Flurazepam 30 mg	Placebo, Lemborexant 10 mg, Lemborexant 5 mg, Flurazepam 30 mg	Total
Female	9	8	10	9	7	8	51
Male	3	3	1	2	5	4	18

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Placebo, Lemborexant 5 mg, Lemborexant 10 mg, Flurazepam 30 mg	Lemborexant 10 mg, Placebo, Lemborexant 5 mg, Flurazepam 30 mg	Lemborexant 5 mg, Lemborexant 10 mg, Placebo, Flurazepam 30 mg	Lemborexant 10 mg, Lemborexant 5 mg, Placebo, Flurazepam 30 mg	Lemborexant 5 mg, Placebo, Lemborexant 10 mg, Flurazepam 30 mg	Placebo, Lemborexant 10 mg, Lemborexant 5 mg, Flurazepam 30 mg	Total
Hispanic or Latino	0	0	0	0	0	0	0
Not Hispanic or Latino	12	11	11	11	12	12	69
Unknown or Not Reported	0	0	0	0	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Placebo, Lemborexant 5 mg, Lemborexant 10 mg, Flurazepam 30 mg	Lemborexant 10 mg, Placebo, Lemborexant 5 mg, Flurazepam 30 mg	Lemborexant 5 mg, Lemborexant 10 mg, Placebo, Flurazepam 30 mg	Lemborexant 10 mg, Lemborexant 5 mg, Placebo, Flurazepam 30 mg	Lemborexant 5 mg, Placebo, Lemborexant 10 mg, Flurazepam 30 mg	Placebo, Lemborexant 10 mg, Lemborexant 5 mg, Flurazepam 30 mg	Total
American Indian or Alaska Native	0	0	0	0	0	0	0
Asian	0	0	0	0	1	0	1
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0
Black or African American	5	7	7	3	6	5	33
White	7	4	4	8	5	7	35
More than one race	0	0	0	0	0	0	0
Unknown or Not Reported	0	0	0	0	0	0	0

Study locations

2 sites

Atlanta, Georgia 30342, United States
Crestview Hills, Kentucky 41017, United States

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jan 18, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02350309
Lead sponsor: Eisai Inc.
Responsible party: Sponsor
First posted: Jan 29, 2015
Start date: Dec 13, 2014
Primary completion: Apr 21, 2015
Completion: Apr 21, 2015
Results posted: Jan 18, 2020
Last update: Jan 18, 2020

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes

View the source record on ClinicalTrials.gov ↗

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