Clinical trial NCT01463098: A 2-Part Single Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of E2006
Official title: A 2-Part, Randomized, Double-Blind, Placebo- and Active- Controlled, Single Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of E2006 in Healthy Subjects and Otherwise Healthy Subjects With Primary Insomnia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Insomnia
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2011-11-01
Enrollment: 122
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


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 \</= 30 minutes
* With typical total sleep time (TST) \>/= 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 \< 15 minutes
* With mean wake after sleep onset (WASO) \>/= 20 minutes on both baseline nights, with neither night \< 15 minutes or mean TST \> 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

Primary outcomes:
measure: Part A: Number of Participants With Treatment Emergent Adverse Events (AEs) and Treatment Emergent Serious Adverse Events (SAEs)
timeFrame: Baseline up to Day 11
measure: Part A: Number of Participants With Markedly Abnormal Laboratory Parameter Values
timeFrame: Baseline up to Day 6
measure: Part A: Number of Participants With Significant Change From Baseline in Vital Sign Values
timeFrame: Baseline up to Day 11
measure: Part A: Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Parameter Values
timeFrame: Baseline up to Day 11
measure: Part A: Number of Participants With Any Suicidality Assessed Using Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline, Day 11
measure: Part B: Change From Baseline in Latency to Persistent Sleep (LPS) Assessed Using Polysomnography (PSG) Measurement at Day 1
timeFrame: Baseline, Day 1
measure: Part B: Change From Baseline in Total Sleep Time (TST) Assessed Using PSG at Day 1
timeFrame: Baseline, Day 1
measure: Part B: Change From Baseline in Sleep Efficiency Assessed Using PSG at Day 1
timeFrame: Baseline, Day 1
measure: Part B: Change From Baseline in Wake After Sleep Onset (WASO) Assessed Using PSG at Day 1
timeFrame: Baseline, Day 1
measure: Part B: Change From Baseline in Number of Awakenings After Persistent Sleep (NAW) Assessed Using PSG at Day 1
timeFrame: Baseline, Day 1
measure: Part B: Change From Baseline in Percentage of Each Sleep Stage Duration Assessed Using PSG at Day 1
timeFrame: Baseline, Day 1
measure: Part B: Change From Baseline in Duration (in Minutes) of Each Sleep Stage Assessed Using PSG at Day 1
timeFrame: Baseline, Day 1
measure: Part B: Change From Baseline in Mean Total Number of Shift in Sleep Stages Assessed Using PSG at Day 1
timeFrame: Baseline, Day 1
measure: Part B: Change From Day 1 in Waketime Questionnaire Parameters: How Long Did You Sleep Last Night at Day 6
timeFrame: Day 1, Day 6
measure: Part B: Change From Day 1 in Waketime Questionnaire Parameters: Time to Fall Asleep Last Night at Day 6
timeFrame: Day 1, Day 6
measure: Part B: Change From Day 1 in Waketime Questionnaire Parameters: Number of Awakening After Falling Asleep at Day 6
timeFrame: Day 1, Day 6
measure: Part B: Change From Day 1 in Waketime Questionnaire Parameters: Time Spent Awake After Falling Asleep at Day 6
timeFrame: Day 1, Day 6
measure: Part B: Change From Day 1 in Waketime Questionnaire Parameters: Rate Quality of Your Sleep at Day 6
timeFrame: Day 1, Day 6
measure: Part B: Change From Day 1 (Pre-dose) in Digit Symbol Substitution Test (DSST) Score at Day 6
timeFrame: Day 1 (Pre-dose), Day 6
measure: 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
timeFrame: Day 1 (Pre-dose), Day 6
measure: Part B: Change From Day 1 (Pre-dose) in Score on Karolinska Sleepiness Scale (KSS) at Day 6
timeFrame: Day 1 (Pre-dose), Day 6
Secondary outcomes:
measure: Part A: Maximum Plasma Concentration (Cmax) of E2006
timeFrame: Day 1: Pre-dose, up to 240 hours post-dose
measure: Part A: Time to Reach Maximum Plasma Concentration (Tmax) of E2006
timeFrame: Day 1: Pre-dose, up to 240 hours post-dose
measure: Part A: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC0-24) of E2006
timeFrame: Day 1: Pre-dose, up to 240 hours post-dose
measure: Part A: Area Under the Plasma Concentration-time Curve From Time Zero to t Hours (AUC0-t) of E2006
timeFrame: Day 1: Pre-dose, up to 240 hours post-dose
measure: Part A: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of E2006
timeFrame: Day 1: Pre-dose, up to 240 hours post-dose
measure: Part A: Terminal Half-life (t1/2) of E2006 in Plasma
timeFrame: Day 1: Pre-dose, up to 240 hours post-dose
measure: Part A: Apparent Total Clearance of E2006 From Plasma (CL/F)
timeFrame: Day 1: Pre-dose, up to 240 hours post-dose
measure: Part A: Apparent Volume of Distribution of E2006 in Plasma (Vz/F)
timeFrame: Day 1: Pre-dose, up to 240 hours post-dose
measure: Part A: Cumulative Amount of Unchanged Drug E2006 Excreted Into the Urine (Ae)
timeFrame: Day 1: Pre-dose, up to 120 hours post-dose
measure: Part A: Renal Clearance (CLR) of Drug E2006
timeFrame: Day 1: Pre-dose, up to 120 hours post-dose
measure: Part A: Maximum Change From Day 1 (Pre-dose) in Digit Symbol Substitution Test (DSST) Score at Day 6
timeFrame: Day 1 (Pre-dose), up to Day 6
measure: 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
timeFrame: Day 1 (Pre-dose), Day 6
measure: Part A: Maximum Change From Day 1 (Pre-dose) in Karolinska Sleepiness Scale (KSS) Score at Day 6
timeFrame: Day 1 (Pre-dose), Day 6
measure: Part A: Change From Day 1 in Waketime Questionnaire Parameters: How Long Did You Sleep Last Night at Day 6
timeFrame: Day 1, Day 6
measure: Part A: Change From Day 1 in Waketime Questionnaire Parameters: Time to Fall Asleep Last Night at Day 6
timeFrame: Day 1, Day 6
measure: Part A: Change From Day 1 in Waketime Questionnaire Parameters: Number of Awakening After Falling Asleep at Day 6
timeFrame: Day 1, Day 6
measure: Part A: Change From Day 1 in Waketime Questionnaire Parameters: Time Spent Awake After Falling Asleep at Day 6
timeFrame: Day 1, Day 6
measure: Part A: Change From Day 1 in Waketime Questionnaire Parameters: Rate Quality of Your Sleep at Day 6
timeFrame: Day 1, Day 6
measure: Part B: Number of Participants With Treatment Emergent Adverse Events (AEs) and Treatment Emergent Serious Adverse Events (SAEs)
timeFrame: Baseline up to Day 11
measure: Part B: Number of Participants With Markedly Abnormal Laboratory Parameter Values
timeFrame: Baseline up to Day 6
measure: Part B: Number of Participants With Significant Change From Baseline in Vital Sign Values
timeFrame: Baseline up to Day 11
measure: Part B: Number of Participants With Clinically Significant Change From Baseline in ECG Parameter Values
timeFrame: Baseline up to Day 11
measure: Part B: Number of Participants With Any Suicidality Assessed Using Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline, Day 11
Other outcomes:
Locations:
city: New York
country: United States
facility: Clinilabs, Inc.
state: New York
city: Cincinnati
country: United States
facility: Community Research
state: Ohio
Study officials:
References: