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Chronic InsomniaPhase 2NCT01995838

A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Bayesian Adaptive Randomization Design, Dose Response Study of the Efficacy of E2006 in Adults and Elderly Subjects With Chronic Insomnia

A Phase 2 study testing E2006 in people with Chronic Insomnia and Adults, run by Eisai Inc. at 29 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a multicenter, multiple dose, randomized, double-blind, placebo-controlled, parallel-group, Bayesian adaptive, dose response study in subjects with chronic insomnia. Subjects will be randomized to 1 of 6 doses of E2006 (1 mg, 2.5 mg, 5 mg, 10 mg, 15 mg, or 25 mg) or placebo. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Chronic Insomnia, Adults, Elderly
What is being tested?
E2006
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
291 participants
Where
29 sitesUnited States
Study dates
13 Nov 2013to 29 Apr 2014
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subjects must meet all of the following criteria to be included in this study:
  • Male or female subjects age 18 to 80 years 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
  • Subjective Sleep Onset Latency (sSOL) typically greater than or equal to 30 minutes in the last 4 weeks and/or subjective WASO (sWASO) typically greater than or equal to 60 minutes in the last 4 weeks
  • Regular time in bed between 6.5 and 9.0 hours
  • Regular bedtime between 21:00 and 24:00 and regular waketime between 05:00 and 09:00
Show all 17Show fewer
  • Insomnia Severity Index (ISI) score greater than or equal to 15 at Screening
  • Confirmation of current insomnia symptoms as determined from responses on the Sleep Diary completed for 7 nights prior to the first screening/baseline PSG
  • Objective (PSG) evidence of insomnia at the screening/baseline PSGs as follows:
  • LPS average greater than or equal to 30 minutes on the 2 consecutive screening/baseline PSGs, with neither night lesser than 15 minutes and/or
  • WASO average greater than or equal to 30 minutes on the 2 consecutive screening/baseline PSGs, with neither night lesser than 20 minutes
  • SE average lesser than or equal to 85% on the 2 consecutive screening/baseline PSGs, with neither night greater than 87.5%
  • Females of childbearing potential must not have had unprotected sexual intercourse within 30 days before study entry and must agree to use two highly effective method of contraception
  • Male subjects must have had a successful vasectomy (confirmed azoospermia) or they and their female partners must meet the criteria above (i.e., not of childbearing potential or practicing highly effective contraception throughout the study period and for 30 days after study drug discontinuation). No sperm donation is allowed during the study period and for 30 days after study drug discontinuation.
  • Provide written informed consent
  • Willing to stay in bed for at least 8 hours each night spent in the clinic
  • Willing and able to comply with all aspects of the protocol

Who cannot join

  • Subjects who meet any of the following criteria will be excluded from this study:
  • Females who are pregnant (positive beta-human chorionic gonadotropin [B-hCG] test) or breastfeeding
  • Any lifetime diagnosis of sleep-related breathing disorder, periodic limb movement disorder, restless legs syndrome, nightmare disorder, sleep terror disorder, sleepwalking disorder, rapid eye movement (REM) behavior disorder, or narcolepsy
  • Aged 18 to 64 years: Apnea-Hypopnea Index greater than or equal to 10, or Periodic Limb Movements with Arousal Index greater than or equal to 10 on first (diagnostic) PSG night at Screening. Aged 65 to 80 years: Apnea-Hypopnea Index greater than 15, or Periodic Limb Movements with Arousal Index greater than 15 on first (diagnostic) PSG night at Screening
  • Beck Depression Inventory (BDI) - II score greater than 19 at Screening
  • Beck Anxiety Inventory (BAI) score greater than 15 at Screening
Show all 26Show fewer
  • Used a prescription for any modality of treatment for insomnia, including cognitive behavioral therapy, within 2 weeks prior to screening/baseline PSG, or between Screening and Baseline
  • Used any medication or sleep aid with known effects on sleep, within 2 weeks prior to screening/baseline PSG, or between Screening and Baseline
  • Used any prohibited prescription or over-the-counter concomitant medications within the week prior to the first screening/baseline PSG.
  • Transmeridian travel across 3 or more time zones in the 2 weeks prior to Screening, or plans to travel across 3 or more time zones during study
  • Unwilling to limit caffeine consumption to lesser than or equal to 600 mg caffeine (approximately four 6-oz cups of caffeinated coffee, or three 12-oz caffeinated sodas, or three 8-oz caffeinated tea beverages), avoid caffeine after 18:00 throughout the study, and avoid caffeine after 13:00 on PSG visits
  • Unwilling to limit alcohol intake to two or fewer drinks per day throughout the study, or to refrain from any alcohol for 3 hours prior to bedtime while at home throughout the study, or any alcohol on days and nights spent in the clinic. A drink is defined as approximately 12 oz (360 mL) of beer, 4 oz (120 mL) of wine, or 1 oz (30 mL) of liquor.
  • Any subject that has a known history of malaria or has traveled to a country with known malarial risk (i.e., are designated as 'high' or 'moderate' risk country according to the list available at http://www.cdc.gov/malaria) within the last year.
  • A prolonged QT/QT interval corrected for heart rate (QTc) interval (QTc greater than 450 ms) as demonstrated by a repeated electrocardiogram (ECG) at Screening (repeated only if initial ECG indicates a QTc interval greater than 450 ms). A history of risk factors for torsade de pointes (e.g., heart failure, hypokalemia, family history of long QT Syndrome) or the use of concomitant medications that prolong the QT/QTc interval.
  • Any suicidal ideation with intent with or without a plan at Screening, Baseline, or within 6 months before Screening (i.e., answering "Yes" to questions 4 or 5 on the Suicidal Ideation section of the Columbia-Suicide Severity Rating Scale [C-SSRS])
  • Any lifetime suicidal behavior (per the Suicidal Behavior Section of the C-SSRS)
  • Evidence of clinically significant disease (e.g., cardiac, respiratory, gastrointestinal, renal disease) that in the opinion of the investigator(s) could affect the subject's safety or interfere with the study assessments
  • Hypersensitivity to the study drug or any of the excipients
  • Any history of a medical condition or a concomitant medical condition that in the opinion of the investigator(s) would compromise the subject's ability to safely complete the study
  • Scheduled for surgery during the study
  • Known to be human immunodeficiency virus (HIV) positive
  • Active viral hepatitis (B or C) as demonstrated by positive serology
  • Psychotic disorder(s) or unstable recurrent affective disorder(s) evident by use of antipsychotics or prior suicide attempt(s) within approximately the last 2 years
  • History of drug or alcohol dependency or abuse within approximately the last 2 years
  • Unwilling to refrain from use of illegal (or legalized) recreational drugs during the study or test positive for illegal (or legalized) drugs at Screening, Baseline, or Day 14
  • Currently enrolled in another clinical trial or used any investigational drug or device within 30 days or 5x the half-life, whichever is longer preceding informed consent

Trial locations and contacts

29 sites in 1 country.

29 sites in 1 country

United States29 sites

  • Study site

    Atlanta, Georgia, 30342

  • Study site

    Austin, Texas, 78731

  • Study site

    Austin, Texas, 78744

  • Study site

    Brandon, Florida, 33511

  • Study site

    Chicago, Illinois, 60634

  • Study site

    Chicago, Illinois, 60637

  • Study site

    Cincinnati, Ohio, 45212

  • Study site

    Cincinnati, Ohio, 45255

  • Study site

    Colorado Springs, Colorado, 80907

  • Study site

    Colorado Springs, Colorado, 80909

  • Study site

    Columbia, South Carolina, 29201-2953

  • Study site

    Dallas, Texas, 75230

  • Study site

    Fountain Valley, California, 92708

  • Study site

    Glen Burnie, Maryland, 21061

  • Study site

    Glendale, Arizona, 85306

  • Study site

    Hallandale, Florida, 33009

  • Study site

    Hollywood, Florida, 33024

  • Study site

    Las Vegas, Nevada, 89104

  • Study site

    New York, New York, 10019

  • Study site

    Oceanside, California, 92054

  • Study site

    Overland Park, Kansas, 66212

  • Study site

    Philadelphia, Pennsylvania, 19118

  • Study site

    Phoenix, Arizona, 85006

  • Study site

    Raleigh, North Carolina, 27612

  • Study site

    San Diego, California, 92103

  • Study site

    San Diego, California, 92123

  • Study site

    South Miami, Florida, 33143

  • Study site

    Thousand Oaks, California, 91360

  • Study site

    Vienna, Virginia, 22182

Other trials in United States

About this study

This is a multicenter, multiple dose, randomized, double-blind, placebo-controlled, parallel-group, Bayesian adaptive, dose response study in subjects with chronic insomnia. Subjects will be randomized to 1 of 6 doses of E2006 (1 mg, 2.5 mg, 5 mg, 10 mg, 15 mg, or 25 mg) or placebo.

Read the detailed description

The study will have 2 phases, Prerandomization and Randomization. The Prerandomization Phase will last up to 21 days and will consist of a Screening Period (Days -21 to -2) and a Baseline Period (Day -1). Following the Baseline Period, all eligible subjects will be randomized, in a double-blind manner, to receive E2006 or placebo for 15 nights during the Treatment Period (Days 1 to 15), then all subjects will receive placebo, in a single-blind manner, for 2 nights (Days 16 to 17) during the Rebound Insomnia Assessment Period (Days 16 to 18). Subjects will not receive any treatment during the Follow-up Period (Days 19 to 29). All subjects will come to the clinic for screening procedures. During the Screening Period, subjects will complete the Sleep Diary each day. Polysomnographic sleep will be measured during the Screening Period on 2 consecutive nights between Day -9 and Day -3. These 8-hour polysomnograms (PSGs) will start at the median habitual bedtime calculated from responses on the Sleep Diary completed 7 days immediately prior to the first PSG night. Subjects may leave the clinic between the screening/baseline PSG nights.

Being tested
E2006, Placebo
Keywords
Chronic Insomnia, Adults, Elderly
Medical subject headings
Sleep Initiation and Maintenance Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • E2006Drug

    E2006 1 mg, 2.5 mg, 5 mg, 10 mg, 15 mg, or 25 mg, in tablet form, taken orally, 30 minutes prior to bedtime, each night for 15 consecutive nights

  • PlaceboDrug

    E2006-matched placebo in tablet form, taken orally, 30 minutes prior to bedtime, each night for 15 consecutive nights

Study groups in NCT01995838
Study groupRoleWhat they receive
E2006ExperimentalE2006 1 mg, 2.5 mg, 5 mg, 10 mg, 15 mg, or 25 mg, in tablet form, taken orally, 30 minutes prior to bedtime, each night for 15 consecutive nights
Receives: Drug: E2006
PlaceboPlacebo comparatorE2006-matched placebo in tablet form, taken orally, 30 minutes prior to bedtime, each night for 15 consecutive nights
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Probability of Having Utility Function Greater Than (>) 1 Based on Bayesian Analysis

    The utility of a dose was a function of both Sleep Efficiency (SE) and Karolinska Sleepiness Scale (KSS), constructed by specifying the 1-dimensional component for each outcome measure and then combining them multiplicatively. Sufficient utility was defined as a probability of having utility function >1. Probability of having utility function >1 at the end of study visit (full analysis) was reported.

    Measured: Baseline up to Day 3

  2. Mean Change From Baseline in Karolinska Sleepiness Scale (KSS) Score at End of Treatment

    The KSS was used to measure next-day residual effects at prespecified time points. The KSS was a 9-point scale on which the participant rated their sleepiness from 1 (extremely alert) to 9 (extremely sleepy/fighting sleep), where higher scores indicated an increase in sleepiness. The end of treatment score was calculated by the mean scores at the timepoint at 1 hour after morning wake time of Day 15 and 16.

    Measured: 1 hour after morning wake time at Baseline and Days 15-16

Secondary outcomes (11)

  1. Mean Change From Baseline in Sleep Efficiency (SE) After Dosing on Days 1-2 and Days 14-15

    Sleep efficiency was calculated as total sleep time divided by time spent in bed multiplied by 100. An increase in SE indicated improvement in sleeping, such that, the participant spends more time in bed asleep. Mean scores of Days 1-2 and Days 14-15 were used to evaluate change from baseline.

    Measured: Baseline, Days 1-2, and Days 14-15

  2. Mean Change From Baseline in Latency to Persistent Sleep (LPS) After Dosing on Days 1-2 and Days 14-15

    LPS was calculated as minutes from lights off to the first 30-second epoch of 20 consecutive epochs of non-wakefulness. A decrease in LPS indicated improvement in time needed to fall asleep. Mean scores of Days 1-2 and Days 14-15 were used to evaluate change from baseline.

    Measured: Baseline, Days 1-2, and Days 14-15

  3. Mean Change From Baseline in Wakefulness After Sleep Onset (WASO) After Dosing on Days 1-2 and Days 14-15

    WASO was calculated as minutes of wakefulness from the onset of persistent sleep until lights on. A decrease in WASO indicated improvement in sleep maintenance. Mean scores of Days 1-2 and Days 14-15 were used to evaluate change from baseline.

    Measured: Baseline, Days 1-2, and Days 14-15

  4. Potential Habituation Effect: Comparison Between Mean Change From Baseline in SE on Days 1-2 and Mean Change From Baseline in SE on Days 14-15

    Potential habituation effect evaluated the possibility of participants being habituated to changes in sleep during the 15 days of treatment with lemborexant. Data reported here was calculated as change from baseline of mean SE of Days 14-15 minus change from baseline of mean SE of Days 1-2. An increase in SE indicated improvement in sleeping, such that, the participant spends more time in bed asleep.

    Measured: Baseline, Days 1-2, and Days 14-15

  5. Potential Habituation Effect: Comparison Between Mean Change From Baseline in Latency to Persistent Sleep (LPS) on Days 1-2 and Mean Change From Baseline in LPS on Days 14-15

    Potential habituation effect evaluated the possibility of participants being habituated to changes in sleep during the 15 days of treatment with lemborexant. Data reported here was calculated as change from baseline of mean LPS of Days 14-15 minus change from baseline of mean LPS of Days 1-2. LPS was calculated as minutes from lights off to the first 30-second epoch of 20 consecutive epochs of non-wakefulness. A decrease in LPS indicated improvement in time needed to fall asleep.

    Measured: Baseline and Days 1-2, and Days 14-15

  6. Potential Habituation Effect: Comparison Between Mean Change From Baseline in Wakefulness After Sleep Onset (WASO) on Days 1-2 and Mean Change From Baseline in WASO on Days 14-15

    Potential habituation effect evaluated the possibility of participants being habituated to changes in sleep during the 15 days of treatment with lemborexant. Data reported here was calculated as change from baseline of mean WASO of Days 14-15 minus change from baseline of mean WASO of Days 1-2. WASO was calculated as minutes of wakefulness from the onset of persistent sleep until lights on. A decrease in WASO indicated improvement in sleep maintenance.

    Measured: Baseline, Days 1-2, and Days 14-15

  7. Rebound Insomnia: Mean Change From Baseline in Sleep Efficiency (SE) After Dosing on Days 16-17

    Rebound insomnia was assessed by comparing the change from baseline of the mean SE on Days 16-17. Sleep efficiency was calculated as total sleep time divided by time spent in bed multiplied by 100. An increase in SE indicated improvement in sleeping, such that, the participant spends more time in bed asleep. A negative change from baseline in SE indicated that SE was worse on Days 16 and 17 than at Baseline, which was considered as evidence for rebound insomnia.

    Measured: Baseline and Days 16-17

  8. Percentage of Participants With Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)

    Measured: TEAEs: Baseline up to Day 30, SAEs: Baseline up to 30 days after last dose of study drug (up to 47 days)

  9. Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Parameters

    Measured: Baseline up to Day 30

  10. Number of Participants With Clinically Significant Change From Baseline in Vital Signs

    Measured: Baseline up to Day 30

  11. Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECGs)

    Measured: Baseline up to Day 30

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Nov 2013 (estimated)
  2. Study start13 Nov 2013
  3. Primary completion29 Apr 2014
  4. Study completion29 Apr 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
291 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01995838
Sponsor's protocol ID
E2006-G000-201
Status last verified
Nov 2015
First submitted
13 Nov 2013
Last updated
31 Jan 2020
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Murphy P, Moline M, Mayleben D, Rosenberg R, Zammit G, Pinner K, Dhadda S, Hong Q, Giorgi L, Satlin A. Lemborexant, A Dual Orexin Receptor Antagonist (DORA) for the Treatment of Insomnia Disorder: Results From a Bayesian, Adaptive, Randomized, Double-Blind, Placebo-Controlled Study. J Clin Sleep Med. 2017 Nov 15;13(11):1289-1299. doi: 10.5664/jcsm.6800.

    PubMed 29065953

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing E2006 in people with Chronic Insomnia and Adults, run by Eisai Inc. at 29 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 29 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Probability of Having Utility Function Greater Than (>) 1 Based on Bayesian Analysis (time frame: Baseline up to Day 3). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01995838, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jan 2020; AzTrials last refreshed its copy on 27 Oct 2026.

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