We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01995838
First Posted: November 27, 2013
Last Update Posted: July 20, 2015
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Eisai Inc.
  Purpose
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.

Condition Intervention Phase
Chronic Insomnia Adults Elderly Drug: E2006 Drug: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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

Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • A utility function combining the change from baseline in mean sleep efficiency and change from baseline in mean subjective sleepiness ratings at the beginning of treatment. [ Time Frame: Baseline, Day 1 and Day 2 for sleep efficiency; Baseline, Day 2 and Day 3 for subjective sleepiness ratings ]
    A utility is a numerical rating assigned to possible primary efficacy and primary next-day residual sleepiness outcomes according to the clinical preference. A greater utility corresponds to a better preference. A utility function is a mathematical function that relates utility to the preference of primary efficacy and primary residual sleepiness outcomes.

  • Change from baseline in mean subjective sleepiness ratings at the end of treatment [ Time Frame: Baseline, Day 15 and Day 16 ]
    Change from baseline to Day 15 and Day 16 in subjective sleepiness ratings.


Secondary Outcome Measures:
  • Efficacy of E2006 at beginning of treatment in terms of sleep efficiency (SE), latency to persistent sleep (LPS), and wakefulness after sleep onset (WASO) [ Time Frame: Baseline, Day 1 and Day 2 ]
    Efficacy will be measured by change from baseline in mean SE, LPS, and WASO on Day 1 and Day 2

  • Efficacy of E2006 at end of treatment in terms of SE, LPS, and WASO [ Time Frame: Baseline, Day 14 and Day 15 ]
    Efficacy will be measured by change from baseline in mean SE, LPS, and WASO on Day 14 and Day 15

  • Potential habituation of efficacy of E2006 from beginning to end of treatment in terms of SE, LPS, and WASO [ Time Frame: Baseline, Day 1, Day 2, Day 14 and Day 15 ]
    Efficacy will be measured by change from baseline in mean SE, LPS, and WASO on Day 1, Day 2, Day 14 and Day 15

  • Change from baseline in mean SE after dosing with placebo [ Time Frame: Baseline, Day 16 and Day 17 ]
    Measuring the rebound insomnia of E2006 after being administered placebo for two days after 15 consecutive days of treatment.


Enrollment: 616
Study Start Date: November 2013
Study Completion Date: May 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: E2006
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
Drug: E2006
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
Placebo Comparator: Placebo
E2006-matched placebo in tablet form, taken orally, 30 minutes prior to bedtime, each night for 15 consecutive nights
Drug: Placebo
E2006-matched placebo in tablet form, taken orally, 30 minutes prior to bedtime, each night for 15 consecutive nights

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.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Subjects must meet all of the following criteria to be included in this study:

  1. Male or female subjects age 18 to 80 years 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
  3. 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
  4. Regular time in bed between 6.5 and 9.0 hours
  5. Regular bedtime between 21:00 and 24:00 and regular waketime between 05:00 and 09:00
  6. Insomnia Severity Index (ISI) score greater than or equal to 15 at Screening
  7. Confirmation of current insomnia symptoms as determined from responses on the Sleep Diary completed for 7 nights prior to the first screening/baseline PSG
  8. Objective (PSG) evidence of insomnia at the screening/baseline PSGs as follows:

    1. 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
    2. WASO average greater than or equal to 30 minutes on the 2 consecutive screening/baseline PSGs, with neither night lesser than 20 minutes
    3. SE average lesser than or equal to 85% on the 2 consecutive screening/baseline PSGs, with neither night greater than 87.5%
  9. 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
  10. 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.
  11. Provide written informed consent
  12. Willing to stay in bed for at least 8 hours each night spent in the clinic
  13. Willing and able to comply with all aspects of the protocol

Exclusion Criteria

Subjects who meet any of the following criteria will be excluded from this study:

  1. Females who are pregnant (positive beta-human chorionic gonadotropin [B-hCG] test) or breastfeeding
  2. 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
  3. 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
  4. Beck Depression Inventory (BDI) - II score greater than 19 at Screening
  5. Beck Anxiety Inventory (BAI) score greater than 15 at Screening
  6. 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
  7. Used any medication or sleep aid with known effects on sleep, within 2 weeks prior to screening/baseline PSG, or between Screening and Baseline
  8. Used any prohibited prescription or over-the-counter concomitant medications within the week prior to the first screening/baseline PSG.
  9. 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
  10. 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
  11. 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.
  12. 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.
  13. 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.
  14. 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])
  15. Any lifetime suicidal behavior (per the Suicidal Behavior Section of the C-SSRS)
  16. 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
  17. Hypersensitivity to the study drug or any of the excipients
  18. 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
  19. Scheduled for surgery during the study
  20. Known to be human immunodeficiency virus (HIV) positive
  21. Active viral hepatitis (B or C) as demonstrated by positive serology
  22. 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
  23. History of drug or alcohol dependency or abuse within approximately the last 2 years
  24. 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
  25. 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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01995838


  Show 23 Study Locations
Sponsors and Collaborators
Eisai Inc.
  More Information

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT01995838     History of Changes
Other Study ID Numbers: E2006-G000-201
First Submitted: November 13, 2013
First Posted: November 27, 2013
Last Update Posted: July 20, 2015
Last Verified: March 2015

Keywords provided by Eisai Inc.:
Chronic Insomnia
Adults
Elderly

Additional relevant MeSH terms:
Sleep Initiation and Maintenance Disorders
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases
Mental Disorders