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

NCT02350309 | Completed Phase 1 Results FDA Drug

• 1 other identifier: E2006-A001-107
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Insomnia Disorder

Keywords

Insomnia Disorder; E2006; Multiple Sleep Latency Test; Lemborexant

Outcome Measures

Primary Outcomes (1)

• 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)

Secondary Outcomes (10)

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

  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

  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

  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

  Baseline, Day 2 of Treatment Period 4 (Week 6)

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

  Days 2, 16 and 30 within 20 minutes after the end of 4th SLT (up to 155 minutes after wake time)

Study Arms (4)

Lemborexant 5 mg

EXPERIMENTAL

Participants will receive a single, oral tablet formulation dose of lemborexant 5 mg within 5 minutes before bedtime.

Drug: Lemborexant 5 mg

Lemborexant 10 mg

EXPERIMENTAL

Participants will receive a single, oral tablet formulation dose of lemborexant 10 mg within 5 minutes before bedtime.

Drug: Lemborexant 10 mg

Lemborexant-matched Placebo

PLACEBO COMPARATOR

Participants will receive a single, oral tablet formulation dose of lemborexant-matched placebo within 5 minutes before bedtime.

Drug: Lemborexant-matched placebo.

Flurazepam 30 mg

ACTIVE COMPARATOR

Participants will receive a single, oral capsule formulation dose of flurazepam 30 mg within 5 minutes before bedtime.

Drug: Flurazepam 30 mg

Interventions

Lemborexant 5 mg DRUG

Lemborexant 5 mg tablet.

Also known as: E2006

Lemborexant 5 mg

Lemborexant 10 mg DRUG

Lemborexant 10 mg tablet.

Also known as: E2006

Lemborexant 10 mg

Lemborexant-matched placebo. DRUG

Lemborexant-matched placebo tablet.

Also known as: E2006

Lemborexant-matched Placebo

Flurazepam 30 mg DRUG

Flurazepam 30 mg capsule.

Flurazepam 30 mg

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.
• Frequency of complaint greater than or equal to 3 times per week.
• Duration of complaint greater than or equal to 3 months.
• 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.

You may not qualify if:

• 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:
• 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.
• 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.
• 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).
• 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.

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (2)

Unknown Facility

Atlanta, Georgia, 30342, United States

Location

Unknown Facility

Crestview Hills, Kentucky, 41017, United States

Location

Related Publications (1)

• 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.

  PMID: 37193566 DERIVED

MeSH Terms

Conditions

Sleep Initiation and Maintenance Disorders

Interventions

lemborexant; Flurazepam

Condition Hierarchy (Ancestors)

Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Intervention Hierarchy (Ancestors)

Benzodiazepinones; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Eisai Medical Information
• Organization: Eisai Inc.

esi_medinfo@eisai.com

+1-888-274-2378

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2015
• First Posted: January 29, 2015
• Study Start: December 13, 2014
• Primary Completion: April 21, 2015
• Study Completion: April 21, 2015
• Last Updated: January 18, 2020
• Results First Posted: January 18, 2020

Record last verified: 2016-12

Locations

US (2)