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

NCT01995838 | Completed Phase 2 Results FDA Drug

• 1 other identifier: E2006-G000-201
• Study Type: interventional
• Target: 291
• Locations: 1 country
• Sites: 29

Brief 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.

Conditions

Chronic Insomnia; Adults; Elderly

Keywords

Chronic Insomnia; Adults; Elderly

Outcome Measures

Primary Outcomes (2)

• 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.

  Baseline up to Day 3

• 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.

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

Secondary Outcomes (11)

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

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

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

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

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

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

• 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

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

• 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

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

Study Arms (2)

E2006

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

E2006 DRUG

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

E2006

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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 \[C-SSRS\])

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (29)

Unknown Facility

Glendale, Arizona, 85306, United States

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Phoenix, Arizona, 85006, United States

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Fountain Valley, California, 92708, United States

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Oceanside, California, 92054, United States

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San Diego, California, 92103, United States

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San Diego, California, 92123, United States

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Thousand Oaks, California, 91360, United States

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Colorado Springs, Colorado, 80907, United States

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Colorado Springs, Colorado, 80909, United States

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Brandon, Florida, 33511, United States

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Hallandale, Florida, 33009, United States

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Hollywood, Florida, 33024, United States

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South Miami, Florida, 33143, United States

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Atlanta, Georgia, 30342, United States

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Chicago, Illinois, 60634, United States

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Chicago, Illinois, 60637, United States

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Overland Park, Kansas, 66212, United States

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Glen Burnie, Maryland, 21061, United States

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Las Vegas, Nevada, 89104, United States

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New York, New York, 10019, United States

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Raleigh, North Carolina, 27612, United States

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Cincinnati, Ohio, 45212, United States

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Cincinnati, Ohio, 45255, United States

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Philadelphia, Pennsylvania, 19118, United States

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Columbia, South Carolina, 29201-2953, United States

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Austin, Texas, 78731, United States

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Austin, Texas, 78744, United States

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Dallas, Texas, 75230, United States

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Vienna, Virginia, 22182, United States

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Related Publications (1)

• 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.

  PMID: 29065953 DERIVED

MeSH Terms

Conditions

Sleep Initiation and Maintenance Disorders

Condition Hierarchy (Ancestors)

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

Results Point of Contact

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

esi_medinfo@eisai.com

1-888-422-4743

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2013
• First Posted: November 27, 2013
• Study Start: November 13, 2013
• Primary Completion: April 29, 2014
• Study Completion: April 29, 2014
• Last Updated: January 31, 2020
• Results First Posted: January 31, 2020

Record last verified: 2015-11

Locations

US (29)