Clinical trial NCT02350309: Study to Evaluate the Effect of 2 Dosage Strengths of Lemborexant (E2006) on a Multiple Sleep Latency Test in Participants With Insomnia Disorder
Official title: A Randomized, Double-Blind, Placebo-Controlled, 3-Way Crossover Study to Evaluate the Effect of 2 Dosage Strengths of E2006 on a Multiple Sleep Latency Test in Subjects With Insomnia Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Insomnia Disorder
Keywords: Insomnia Disorder
E2006
Multiple Sleep Latency Test
Lemborexant
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2015-01-29
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: Inclusion Criteria:

1. Male or female, age 18 or older, at the time of informed consent.
2. 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.
3. Insomnia Severity Index score greater than or equal to 15 at Screening.
4. Regular time in bed between 7 and 9 hours as reported at Screening.
5. 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.
6. 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:

1. Excessive morning sleepiness at Baseline as determined by average SOL at Baseline less than 10 minutes.
2. 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).
3. 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).
4. 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.
5. 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.
6. Habitually naps more than 3 times per week.
7. History of drug or alcohol dependency or abuse within approximately the last 2 years.
8. Has a positive drug screen at Screening.
9. 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).
10. Any suicidal ideation with intent with or without a plan at Screening or within 6 months of Screening or any lifetime suicidal behavior.
11. 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.
12. Used any prohibited prescription or over-the-counter concomitant medications within 2 weeks prior to Screening, or between Screening and Randomization.
13. Used any modality of treatment for insomnia, including cognitive behavioral therapy or marijuana within 2 weeks prior to Screening, or between Screening and Randomization.
14. Scheduled for surgery during the study.
15. 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.
16. Hypersensitivity to flurazepam, the study drug, or any of the excipients.
17. 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.

Primary outcomes:
measure: 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
timeFrame: 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:
measure: Number of Participants With an Average SOL of Less Than (<) 8.0 Minutes for Each Treatment
timeFrame: Day 2 of each of three treatment periods that were separated by approximately 2 weeks (for a total of up to 6 weeks)
measure: Number of Participants Whose Treatment Difference (Under Either Dose of Lemborexant) Average SOL Score is More Than (>) 6.0 Minutes Shorter Than Placebo
timeFrame: Day 2 of each of three treatment periods that are separated by approximately 2 weeks (for a total of up to 6 weeks)
measure: Number of Participants Whose Average SOL is <8.0 Minutes and >6.0 Minutes Shorter Than Placebo
timeFrame: Day 2 of each of three treatment periods that are separated by approximately 2 weeks (for a total of up to 6 weeks)
measure: Mean Change From Baseline in the Average SOL From the M-MSLT in Treatment Period 4
timeFrame: Baseline, Day 2 of Treatment Period 4 (Week 6)
measure: Mean Plasma Concentrations of Lemborexant and Metabolite M10 in the Morning Following M-MSLT
timeFrame: Days 2, 16 and 30 within 20 minutes after the end of 4th SLT (up to 155 minutes after wake time)
measure: 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
timeFrame: From first dose of study drug up to Day 54
measure: Number of Participants With Clinically Significant Abnormal Laboratory Values
timeFrame: From first dose of study drug up to Day 54
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Signs Values
timeFrame: From first dose of study drug up to Day 54
measure: Number of Participants With Clinically Significant Shifts From Baseline in Electrocardiogram (ECG) Parameters
timeFrame: From first dose of study drug up to Day 54
measure: Relationship Between PK Concentrations of Lemborexant and Sleepiness as Measured by M-MSLT
timeFrame: Baseline up to Day 44 (Week 6)
Other outcomes:
Locations:
city: Atlanta
country: United States
state: Georgia
city: Crestview Hills
country: United States
state: Kentucky
Study officials:
References: