Phase 1
Completed N=64
A 2-Part Single Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of E2006
Source: ClinicalTrials.gov NCT01463098 ↗Enrolled (actual)
64
Serious AEs
0.0%
Results posted
Jan 2020
Primary outcomePrimary: Part A: Number of Participants With Treatment Emergent Adverse Events (AEs) and Treatment Emergent Serious Adverse Events (SAEs) — 7; 1; 0; 1 Participants
Summary
Part A: The purpose of this study is to evaluate the safety and tolerability of single oral doses of E2006 administered in the morning to healthy male and female subjects.
Part B: The purpose of this study is to evaluate selected pharmacodynamic (PD) parameters (e.g., polysomnographically defined sleep measures) with regard to dose response in subjects with primary insomnia following single oral dosing of E2006 in the evening approximately 30 minutes prior to the sleep period, compared with 10 mg zolpidem and placebo.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part A: Number of Participants With Treatment Emergent Adverse Events (AEs) and Treatment Emergent Serious Adverse Events (SAEs) |
7; 1; 0; 1; 4; 2 | — |
| PRIMARY Part A: Number of Participants With Markedly Abnormal Laboratory Parameter Values |
6; 1; 3; 1; 2; 2 | — |
| PRIMARY Part A: Number of Participants With Significant Change From Baseline in Vital Sign Values |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part A: Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Parameter Values |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part A: Number of Participants With Any Suicidality Assessed Using Columbia-Suicide Severity Rating Scale (C-SSRS) |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part B: Change From Baseline in Latency to Persistent Sleep (LPS) Assessed Using Polysomnography (PSG) Measurement at Day 1 |
56.3; 51.8; 50.1; 55.9; 62.8; -7.17 | — |
| PRIMARY Part B: Change From Baseline in Total Sleep Time (TST) Assessed Using PSG at Day 1 |
335; 349; 341; 345; 342; 14.0 | — |
| PRIMARY Part B: Change From Baseline in Sleep Efficiency Assessed Using PSG at Day 1 |
69.8; 72.7; 71.1; 71.9; 71.3; 2.90 | — |
| PRIMARY Part B: Change From Baseline in Wake After Sleep Onset (WASO) Assessed Using PSG at Day 1 |
95.7; 85.7; 95.6; 84.7; 85.4; -7.52 | — |
| PRIMARY Part B: Change From Baseline in Number of Awakenings After Persistent Sleep (NAW) Assessed Using PSG at Day 1 |
10.5; 12.4; 11.9; 12.3; 10.9; 0.125 | — |
| PRIMARY Part B: Change From Baseline in Percentage of Each Sleep Stage Duration Assessed Using PSG at Day 1 |
11.8; 10.3; 15.2; 11.9; 11.5; 0.00429 | — |
| PRIMARY Part B: Change From Baseline in Duration (in Minutes) of Each Sleep Stage Assessed Using PSG at Day 1 |
37.8; 35.1; 50.1; 40.7; 38.9; 2.38 | — |
| PRIMARY Part B: Change From Baseline in Mean Total Number of Shift in Sleep Stages Assessed Using PSG at Day 1 |
167; 168; 174; 188; 153; 0.250 | — |
| PRIMARY Part B: Change From Day 1 in Waketime Questionnaire Parameters: How Long Did You Sleep Last Night at Day 6 |
302.1; 292.3; 298.8; 302.5; 276.3; -3.3 | — |
| PRIMARY Part B: Change From Day 1 in Waketime Questionnaire Parameters: Time to Fall Asleep Last Night at Day 6 |
70.8; 67.3; 72.2; 82.5; 108.1; 8.3 | — |
| PRIMARY Part B: Change From Day 1 in Waketime Questionnaire Parameters: Number of Awakening After Falling Asleep at Day 6 |
2.7; 2.7; 2.8; 2.7; 3.6; -0.1 | — |
| PRIMARY Part B: Change From Day 1 in Waketime Questionnaire Parameters: Time Spent Awake After Falling Asleep at Day 6 |
133.8; 101.8; 82.3; 102.0; 128.8; -27.9 | — |
| PRIMARY Part B: Change From Day 1 in Waketime Questionnaire Parameters: Rate Quality of Your Sleep at Day 6 |
2.8; 3.1; 2.6; 2.6; 2.8; -0.6 | — |
| PRIMARY Part B: Change From Day 1 (Pre-dose) in Digit Symbol Substitution Test (DSST) Score at Day 6 |
53.0; 50.7; 48.2; 51.0; 49.5; 9.8 | — |
| PRIMARY Part B: Change From Day 1 (Pre-dose) in Number of Lapses of Greater Than (>) 500- Milliseconds (Msec) Assessed by Psychomotor Vigilance Test (PVT) at Day 6 |
2.3; 3.0; 4.1; 4.4; 5.2; 0.3 | — |
| PRIMARY Part B: Change From Day 1 (Pre-dose) in Score on Karolinska Sleepiness Scale (KSS) at Day 6 |
4.4; 3.8; 4.0; 4.8; 5.5; -0.4 | — |
| SECONDARY Part A: Maximum Plasma Concentration (Cmax) of E2006 |
5.15; 14.9; 22.3; 32.0; 107; 161 | — |
| SECONDARY Part A: Time to Reach Maximum Plasma Concentration (Tmax) of E2006 |
1.000; 1.010; 1.550; 1.000; 2.010; 2.525 | — |
| SECONDARY Part A: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC0-24) of E2006 |
17.0; 53.8; 93.2; 150; 648; 1060 | — |
| SECONDARY Part A: Area Under the Plasma Concentration-time Curve From Time Zero to t Hours (AUC0-t) of E2006 |
18.4; 74.4; 126; 274; 1390; 1960 | — |
| SECONDARY Part A: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of E2006 |
19.5; 72.3; 146; 299; 1470; 2020 | — |
| SECONDARY Part A: Terminal Half-life (t1/2) of E2006 in Plasma |
12.700; 30.100; 31.350; 56.150; 65.500; 51.850 | — |
| SECONDARY Part A: Apparent Total Clearance of E2006 From Plasma (CL/F) |
44.8; 28.2; 33.9; 33.4; 17.0; 24.8 | — |
| SECONDARY Part A: Apparent Volume of Distribution of E2006 in Plasma (Vz/F) |
1170; 1200; 1610; 2670; 1580; 1810 | — |
| SECONDARY Part A: Cumulative Amount of Unchanged Drug E2006 Excreted Into the Urine (Ae) |
0.000108; 0.0000777; 0.000667; 0.00141; 0.00788; 0.0113 | — |
| SECONDARY Part A: Renal Clearance (CLR) of Drug E2006 |
0.0877; 0.0157; 0.0881; 0.0938; 0.111; 0.107 | — |
| SECONDARY Part A: Maximum Change From Day 1 (Pre-dose) in Digit Symbol Substitution Test (DSST) Score at Day 6 |
53.7; 59.1; 52.3; 63.7; 61.2; 60.5 | — |
| SECONDARY Part A: Maximum Change From Day 1 (Pre-dose) in Number of Lapses of > 500 Msec Assessed by Psychomotor Vigilance Test (PVT) at Day 6 |
1.0; 1.8; 1.3; 2.5; 1.3; 1.5 | — |
| SECONDARY Part A: Maximum Change From Day 1 (Pre-dose) in Karolinska Sleepiness Scale (KSS) Score at Day 6 |
5.2; 2.8; 3.2; 3.8; 3.5; 3.0 | — |
| SECONDARY Part A: Change From Day 1 in Waketime Questionnaire Parameters: How Long Did You Sleep Last Night at Day 6 |
457.7; 475.0; 443.3; 436.7; 473.3; 469.2 | — |
| SECONDARY Part A: Change From Day 1 in Waketime Questionnaire Parameters: Time to Fall Asleep Last Night at Day 6 |
13.2; 15.7; 17.2; 14.5; 15.0; 16.7 | — |
| SECONDARY Part A: Change From Day 1 in Waketime Questionnaire Parameters: Number of Awakening After Falling Asleep at Day 6 |
1.1; 1.8; 1.3; 0.8; 0.5; 1.2 | — |
| SECONDARY Part A: Change From Day 1 in Waketime Questionnaire Parameters: Time Spent Awake After Falling Asleep at Day 6 |
4.6; 6.2; 16.8; 5.3; 1.7; 5.0 | — |
| SECONDARY Part A: Change From Day 1 in Waketime Questionnaire Parameters: Rate Quality of Your Sleep at Day 6 |
1.1; 0.3; 1.5; 0.7; 1.0; 0.5 | — |
| SECONDARY Part B: Number of Participants With Treatment Emergent Adverse Events (AEs) and Treatment Emergent Serious Adverse Events (SAEs) |
1; 6; 2; 6; 6; 0 | — |
| SECONDARY Part B: Number of Participants With Markedly Abnormal Laboratory Parameter Values |
3; 6; 4; 3; 7 | — |
| SECONDARY Part B: Number of Participants With Significant Change From Baseline in Vital Sign Values |
0; 0; 0; 0; 0 | — |
| SECONDARY Part B: Number of Participants With Clinically Significant Change From Baseline in ECG Parameter Values |
0; 0; 0; 0; 0 | — |
| SECONDARY Part B: Number of Participants With Any Suicidality Assessed Using Columbia-Suicide Severity Rating Scale (C-SSRS) |
2; 0; 0; 0; 0; 0 | — |
Eligibility Criteria
Key Inclusion Criteria
Healthy Subjects:
- With habitual time in bed > 7 hours, with lights out 2200 to 2400 and lights on 0600 to 0800
- Who report typical sleep latency of /= 420 minutes
Primary Insomnia Subjects:
- Otherwise healthy adult male and female subjects with a diagnosis of primary insomnia (as defined by the Diagnostic and Statistical Manual of Mental Disorders-IV-Text Revision [DSM-IV-TR]) present at the time of Screening for at least 3 months
- With a score of > 15 on the Insomnia Severity Index (ISI) at Screening
- Who report taking >/= 30 minutes to fall asleep on at least 3 nights per week for the past month
- Who report 6.5 hours sleep or less on at least 3 nights per week for the past month
- With mean latency to persistent sleep (LPS) on both baseline nights of >/= 20 minutes with neither night /= 20 minutes on both baseline nights, with neither night 420 minutes
Key Exclusion Criteria
- With a current history of sleep disorders (e.g., obstructive sleep apnea, restless leg syndrome [RLS], narcolepsy, or circadian rhythm disorder) other than primary insomnia (for Part B)
- Subjects with any clinically abnormal symptom or organ impairment found in medical history, symptoms/signs, vital signs, ECG finding, or laboratory test results which require medical treatment
- All females must be of non-childbearing potential
- With a known history of significant neurological or serious psychiatric illness
Data sourced from ClinicalTrials.gov (NCT01463098). 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.