Phase 2
Completed N=291
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
Insomnia · Adults · Elderly
Source: ClinicalTrials.gov NCT01995838 ↗
Enrolled (actual)
291
Serious AEs
0.7%
Results posted
Jan 2020
Primary outcomePrimary: Probability of Having Utility Function Greater Than (>) 1 Based on Bayesian Analysis — 0.8789; 0.8920; 0.9032; 0.9406 probability
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Probability of Having Utility Function Greater Than (>) 1 Based on Bayesian Analysis |
0.8789; 0.8920; 0.9032; 0.9406; 0.9866; 0.9675 | — |
| PRIMARY Mean Change From Baseline in Karolinska Sleepiness Scale (KSS) Score at End of Treatment |
0.29; -0.10; 0.20; -0.22; 0.16; 0.45 | 0.0651 |
| SECONDARY Mean Change From Baseline in Sleep Efficiency (SE) After Dosing on Days 1-2 and Days 14-15 |
18.72; 18.59; 19.89; 22.25; 24.22; 24.28 | 0.0083 sig |
| SECONDARY Mean Change From Baseline in Latency to Persistent Sleep (LPS) After Dosing on Days 1-2 and Days 14-15 |
-42.92; -52.74; -47.72; -46.80; -51.59; -50.16 | 0.1407 |
| SECONDARY Mean Change From Baseline in Wakefulness After Sleep Onset (WASO) After Dosing on Days 1-2 and Days 14-15 |
-52.11; -43.33; -52.29; -60.84; -70.38; -66.87 | 0.1050 |
| SECONDARY 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 |
-4.04; -0.54; 0.06; -0.68; -2.33; -2.15 | — |
| SECONDARY 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 |
2.71; -1.50; -4.60; -7.93; -1.11; 1.38 | — |
| SECONDARY 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 |
17.98; 2.16; 2.68; 9.30; 11.76; 9.28 | — |
| SECONDARY Rebound Insomnia: Mean Change From Baseline in Sleep Efficiency (SE) After Dosing on Days 16-17 |
13.12; 15.53; 17.67; 13.78; 18.58; 17.12 | 0.1483 |
| SECONDARY Percentage of Participants With Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) |
34.4; 40.7; 42.1; 59.4; 55.4; 60.0 | — |
| SECONDARY Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Parameters |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Clinically Significant Change From Baseline in Vital Signs |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECGs) |
0; 0; 0; 0; 0; 0 | — |
Eligibility Criteria
Inclusion Criteria
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
- 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
Exclusion Criteria
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
Data sourced from ClinicalTrials.gov (NCT01995838). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.