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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lemborexant 5 mg | Experimental | Participants will receive a single, oral tablet formulation dose of lemborexant 5 mg within 5 minutes before bedtime. |
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| Lemborexant 10 mg | Experimental | Participants will receive a single, oral tablet formulation dose of lemborexant 10 mg within 5 minutes before bedtime. |
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| Lemborexant-matched Placebo | Placebo Comparator | Participants will receive a single, oral tablet formulation dose of lemborexant-matched placebo within 5 minutes before bedtime. |
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| Flurazepam 30 mg | Active Comparator | Participants will receive a single, oral capsule formulation dose of flurazepam 30 mg within 5 minutes before bedtime. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lemborexant 5 mg | Drug | Lemborexant 5 mg tablet. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline, Day 2 of each of three treatment periods that were separated by approximately 2 weeks (for a total of up to 4 weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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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:
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:
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:
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.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Atlanta | Georgia | 30342 | United States | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37193566 | Derived | Mayleben D, Rosenberg R, Pinner K, Hussein Z, Moline M. Assessment of morning sleep propensity with lemborexant in adults with insomnia disorder in a randomized, placebo-controlled crossover study. Sleep Adv. 2021 Jul 2;2(1):zpab011. doi: 10.1093/sleepadvances/zpab011. eCollection 2021. |
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A total of 123 participants were screened, of which 54 participants were screen failures and 69 participants were randomized to receive study treatment.
Participants took part in the study at 2 investigative sites in the United Sates from 13 December 2014 to 21 April 2015.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo, Lemborexant 5 mg, Lemborexant 10 mg, Flurazepam 30 mg | Participants received a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Period 1, followed by a single oral dose of lemborexant 5 milligrams (mg) tablet, on Day 1 of Treatment Period 2, followed by a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Period 3, followed by a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4. All doses were administered within 5 minutes before bedtime. A washout period of 12 to 16 days was maintained between the 2 treatment periods. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Treatment Period 1 (2 Days) |
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| Lemborexant 10 mg | Drug | Lemborexant 10 mg tablet. |
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| Lemborexant-matched placebo. | Drug | Lemborexant-matched placebo tablet. |
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| Flurazepam 30 mg | Drug | Flurazepam 30 mg capsule. |
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| 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. | 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. | 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. | 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. | 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 | From first dose of study drug up to Day 54 |
| Number of Participants With Clinically Significant Abnormal Laboratory Values | From first dose of study drug up to Day 54 |
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs Values | From first dose of study drug up to Day 54 |
| Number of Participants With Clinically Significant Shifts From Baseline in Electrocardiogram (ECG) Parameters | 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. | Baseline up to Day 44 (Week 6) |
| Crestview Hills |
| Kentucky |
| 41017 |
| United States |
| FG001 | Lemborexant 10 mg, Placebo, Lemborexant 5 mg, Flurazepam 30 mg | Participants received a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Period 1, followed by a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Period 2, followed by a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Period 3, followed by a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4. All doses were administered within 5 minutes before bedtime. A washout period of 12 to 16 days was maintained between the 2 treatment periods. |
| FG002 | Lemborexant 5 mg, Lemborexant 10 mg, Placebo, Flurazepam 30 mg | Participants received a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Period 1, followed by a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Period 2, followed by a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Period 3, followed by a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4. All doses were administered within 5 minutes before bedtime. A washout period of 12 to 16 days was maintained between the 2 treatment periods. |
| FG003 | Lemborexant 10 mg, Lemborexant 5 mg, Placebo, Flurazepam 30 mg | Participants received a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Period 1, followed by a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Period 2, followed by a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Period 3, followed by a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4. All doses were administered within 5 minutes before bedtime. A washout period of 12 to 16 days was maintained between the 2 treatment periods. |
| FG004 | Lemborexant 5 mg, Placebo, Lemborexant 10 mg, Flurazepam 30 mg | Participants received a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Period 1, followed by a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Period 2, followed by a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Period 3, followed by a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4. All doses were administered within 5 minutes before bedtime. A washout period of 12 to 16 days was maintained between the 2 treatment periods. |
| FG005 | Placebo, Lemborexant 10 mg, Lemborexant 5 mg, Flurazepam 30 mg | Participants received a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Period 1, followed by a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Period 2, followed by a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Period 3, followed by a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4. All doses were administered within 5 minutes before bedtime. A washout period of 12 to 16 days was maintained between the 2 treatment periods. |
| COMPLETED |
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| NOT COMPLETED |
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| Washout Period 1 (12-16 Days) |
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| Treatment Period 2 (2 Days) |
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| Washout Period 2 (12-16 Days) |
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| Treatment Period 3 (2 Days) |
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| Washout Period 3 (12-16 Days) |
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| Treatment Period 4 (2 Days) |
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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.
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo, Lemborexant 5 mg, Lemborexant 10 mg, Flurazepam 30 mg | Participants received a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Period 1, followed by a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Period 2, followed by a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Period 3, followed by a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4. All doses were administered within 5 minutes before bedtime. A washout period of 12 to 16 days was maintained between the 2 treatment periods. |
| BG001 | Lemborexant 10 mg, Placebo, Lemborexant 5 mg, Flurazepam 30 mg | Participants received a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Period 1, followed by a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Period 2, followed by a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Period 3, followed by a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4. All doses were administered within 5 minutes before bedtime. A washout period of 12 to 16 days was maintained between the 2 treatment periods. |
| BG002 | Lemborexant 5 mg, Lemborexant 10 mg, Placebo, Flurazepam 30 mg | Participants received a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Period 1, followed by a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Period 2, followed by a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Period 3, followed by a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4. All doses were administered within 5 minutes before bedtime. A washout period of 12 to 16 days was maintained between the 2 treatment periods. |
| BG003 | Lemborexant 10 mg, Lemborexant 5 mg, Placebo, Flurazepam 30 mg | Participants received a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Period 1, followed by a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Period 2, followed by a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Period 3, followed by a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4. All doses were administered within 5 minutes before bedtime. A washout period of 12 to 16 days was maintained between the 2 treatment periods. |
| BG004 | Lemborexant 5 mg, Placebo, Lemborexant 10 mg, Flurazepam 30 mg | Participants received a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Period 1, followed by a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Period 2, followed by a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Period 3, followed by a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4. All doses were administered within 5 minutes before bedtime. A washout period of 12 to 16 days was maintained between the 2 treatment periods. |
| BG005 | Placebo, Lemborexant 10 mg, Lemborexant 5 mg, Flurazepam 30 mg | Participants received a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Period 1, followed by a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Period 2, followed by a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Period 3, followed by a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4. All doses were administered within 5 minutes before bedtime. A washout period of 12 to 16 days was maintained between the 2 treatment periods. |
| BG006 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants | No |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants | No |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The full analysis set (FAS) was the group of randomized participants who received at least 1 dose of study drug and had at least 1 postdose pharmacodynamics (PD) measurement. | Posted | Mean | Standard Deviation | minutes | Baseline, Day 2 of each of three treatment periods that were separated by approximately 2 weeks (for a total of up to 4 weeks) |
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| Secondary | 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. | The FAS was the group of randomized participants who received at least 1 dose of study drug and had at least 1 postdose PD measurement. | Posted | Count of Participants | Participants | Day 2 of each of three treatment periods that were separated by approximately 2 weeks (for a total of up to 6 weeks) |
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| Secondary | 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. | The FAS was the group of randomized participants who received at least 1 dose of study drug and had at least 1 postdose PD measurement. Participants who were evaluable for this given measure at a given time point were included for this assessment. | Posted | Count of Participants | Participants | Day 2 of each of three treatment periods that are separated by approximately 2 weeks (for a total of up to 6 weeks) |
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| Secondary | 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. | The FAS was the group of randomized participants who received at least 1 dose of study drug and had at least 1 postdose PD measurement. Participants who were evaluable for this given measure at a given time point were included for this assessment. | Posted | Count of Participants | Participants | Day 2 of each of three treatment periods that are separated by approximately 2 weeks (for a total of up to 6 weeks) |
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| Secondary | 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. | The FAS was the group of randomized participants who received at least 1 dose of study drug and had at least 1 postdose PD measurement. | Posted | Mean | Standard Deviation | minutes | Baseline, Day 2 of Treatment Period 4 (Week 6) |
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| Secondary | 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. | The pharmacokinetic (PK) analysis set was the group of participants who received at least one dose of lemborexant and had at least one quantifiable postdose drug concentration. The PK analysis set where data at specified time points was available. | Posted | Mean | Standard Deviation | nanogram per milliliter (ng/mL) | Days 2, 16 and 30 within 20 minutes after the end of 4th SLT (up to 155 minutes after wake time) |
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| Secondary | 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 | 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. | Posted | Count of Participants | Participants | From first dose of study drug up to Day 54 |
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| Secondary | Number of Participants With Clinically Significant Abnormal Laboratory Values | 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. | Posted | Count of Participants | Participants | From first dose of study drug up to Day 54 |
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| Secondary | Number of Participants With Clinically Significant Change From Baseline in Vital Signs Values | 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. | Posted | Count of Participants | Participants | From first dose of study drug up to Day 54 |
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| Secondary | Number of Participants With Clinically Significant Shifts From Baseline in Electrocardiogram (ECG) Parameters | 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. | Posted | Count of Participants | Participants | From first dose of study drug up to Day 54 |
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| Secondary | 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. | The PK analysis set was the group of participants who received at least one dose of E2006 and had at least one quantifiable postdose drug concentration. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure. | Posted | Number | correlation coefficient | Baseline up to Day 44 (Week 6) |
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From date of first dose of study drug up to Day 54
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Lemborexant-matched Placebo | Participants received a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Periods 1, 2, or 3. | 0 | 68 | 0 | 68 | 2 | 68 |
| EG001 | Lemborexant 5 mg | Participants received a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Periods 1, 2, or 3. | 0 | 69 | 0 | 69 | 5 | 69 |
| EG002 | Lemborexant 10 mg | Participants received a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Periods 1, 2, or 3. | 0 | 68 | 0 | 68 | 8 | 68 |
| EG003 | Flurazepam 30 mg | Participants received a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4. | 0 | 68 | 0 | 68 | 5 | 68 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
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| Dry mouth | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA (17.1) | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA (17.1) | Systematic Assessment |
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| Dysgeusia | Nervous system disorders | MedDRA (17.1) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (17.1) | Systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA (17.1) | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA (17.1) | Systematic Assessment |
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| Hypnopompic hallucination | Psychiatric disorders | MedDRA (17.1) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Eisai Medical Information | Eisai Inc. | +1-888-274-2378 | esi_medinfo@eisai.com |
| ID | Term |
|---|---|
| D007319 | Sleep Initiation and Maintenance Disorders |
| ID | Term |
|---|---|
| D020919 | Sleep Disorders, Intrinsic |
| D020920 | Dyssomnias |
| D012893 | Sleep Wake Disorders |
| D009422 | Nervous System Diseases |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| C000634104 | lemborexant |
| D005479 | Flurazepam |
| ID | Term |
|---|---|
| D001570 | Benzodiazepinones |
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Mixed Models Analysis |
| <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 |
| 1-Sided |
| 95 |
| -4.46 |
| Superiority or Other (legacy) |
| OG002 | Lemborexant 10 mg | Participants received a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Periods 1, 2, or 3. |
| OG003 | Flurazepam 30 mg | Participants received a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4. |
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|
|
Participants received a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Periods 1, 2, or 3. |
| OG002 | Flurazepam 30 mg | Participants received a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4. |
|
|
Participants received a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Periods 1, 2, or 3.
| OG002 | Flurazepam 30 mg | Participants received a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4. |
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