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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
122
E2006 1.0 mg capsule.
E2006 2.5 mg capsule.
E2006 5.0 mg (2 capsules of 2.5 mg each).
Clinilabs, Inc.
New York, New York, United States
Community Research
Cincinnati, Ohio, United States
Part A: Number of Participants With Treatment Emergent Adverse Events (AEs) and Treatment Emergent Serious Adverse Events (SAEs)
Time frame: Baseline up to Day 11
Part A: Number of Participants With Markedly Abnormal Laboratory Parameter Values
Time frame: Baseline up to Day 6
Part A: Number of Participants With Significant Change From Baseline in Vital Sign Values
Time frame: Baseline up to Day 11
Part A: Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Parameter Values
Time frame: Baseline up to Day 11
Part A: Number of Participants With Any Suicidality Assessed Using Columbia-Suicide Severity Rating Scale (C-SSRS)
The C-SSRS (mapped to Columbia Classification Algorithm of Suicide Assessment \[C-CASA\]) is an interview-based rating scale to systematically assess any suicidality, any suicidal behavior, any suicidal ideation. Any suicidality: emergence of any suicidal ideation or suicidal behavior. Any suicidal behavior: when response is "yes" for any these questions- actual attempt to suicide, engaged in non-suicidal self-injurious behavior, interrupted attempt, aborted attempt, preparatory acts. Any suicidal ideation: when response is "yes" for any of these questions- wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent to suicide. Number of Participants with any suicidality has been reported for this outcome measure.
Time frame: Baseline, Day 11
Part B: Change From Baseline in Latency to Persistent Sleep (LPS) Assessed Using Polysomnography (PSG) Measurement at Day 1
LPS was the duration of time in minutes from lights off to the first 30 seconds of recording (epoch) of 20 consecutive epochs of non-wakefulness as measured by PSG.
Time frame: Baseline, Day 1
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E2006 10.0 mg capsule.
E2006 25.0 mg (2 capsules of 10 mg each and 2 capsules of 2.5 mg each).
E2006 50.0 mg capsule.
E2006 100 mg (2 capsules of 50 mg each).
E2006 200 mg (4 capsules of 50 mg each).
Zolpidem 10 mg immediate release tablet.
E2006-matched placebo capsules or zolpidem-matched placebo tablets.
E2006-matched placebo capsule.
Part B: Change From Baseline in Total Sleep Time (TST) Assessed Using PSG at Day 1
TST was the duration in minutes including rapid eye movement (REM) sleep plus non-rapid eye movement (NREM) sleep during the time spent in bed.
Time frame: Baseline, Day 1
Part B: Change From Baseline in Sleep Efficiency Assessed Using PSG at Day 1
Sleep efficiency was defined as the TST divided by the time in bed (minutes) multiplied by 100. TST was the duration in minutes including REM sleep plus NREM sleep during the time spent in bed.
Time frame: Baseline, Day 1
Part B: Change From Baseline in Wake After Sleep Onset (WASO) Assessed Using PSG at Day 1
WASO was defined as the duration (in minutes) of wakefulness from onset of persistent sleep to lights-on.
Time frame: Baseline, Day 1
Part B: Change From Baseline in Number of Awakenings After Persistent Sleep (NAW) Assessed Using PSG at Day 1
Number of awakenings was determined from LPS to lights-on. LPS was the duration of time measured from lights off to the first 30 seconds of PSG measurement recording (epoch) of 20 consecutive epochs of non-wake. An awakening was defined as a PSG recording of at least two consecutive wake epochs.
Time frame: Baseline, Day 1
Part B: Change From Baseline in Percentage of Each Sleep Stage Duration Assessed Using PSG at Day 1
Sleep stages included NREM sleep and REM (dreaming) sleep. Non-REM sleep is comprised of the sum of Stage N1 (light sleep), N2 (also fairly light, with sudden increases in brain wave frequency known as sleep spindles) and N3 or slow wave sleep (deep sleep). Sleep was staged in sequential 30-second epochs.
Time frame: Baseline, Day 1
Part B: Change From Baseline in Duration (in Minutes) of Each Sleep Stage Assessed Using PSG at Day 1
Sleep stages included NREM sleep and REM (dreaming) sleep. Non-REM sleep is comprised of the sum of Stage N1 (light sleep), N2 (also fairly light, with sudden increases in brain wave frequency known as sleep spindles) and N3 or slow wave sleep (deep sleep). Sleep was staged in sequential 30-second epochs.
Time frame: Baseline, Day 1
Part B: Change From Baseline in Mean Total Number of Shift in Sleep Stages Assessed Using PSG at Day 1
Sleep stages included NREM sleep and REM (dreaming) sleep. Non-REM sleep is comprised of the sum of Stage N1 (light sleep), N2 (also fairly light, with sudden increases in brain wave frequency known as sleep spindles) and N3 or slow wave sleep (deep sleep). Sleep was staged in sequential 30-second epochs.
Time frame: Baseline, Day 1
Part B: Change From Day 1 in Waketime Questionnaire Parameters: How Long Did You Sleep Last Night at Day 6
Participants were asked to answer the following question using Waketime Questionnaire: How long did you sleep last night, number of awakening after falling asleep, time to fall asleep last night, time spent awake after falling asleep, rate quality of your sleep (using Likert scale, ranged from 0 = very sound or restful, to 4 = very restless where lower score indicates better outcome). The primary purpose of the Waketime Questionnaire was to confirm anticipated reports of poor sleep. In this outcome measure, data for question "How long did you sleep last night" has been reported.
Time frame: Day 1, Day 6
Part B: Change From Day 1 in Waketime Questionnaire Parameters: Time to Fall Asleep Last Night at Day 6
Participants were asked to answer the following question using Waketime Questionnaire: How long did you sleep last night, number of awakening after falling asleep, time to fall asleep last night, time spent awake after falling asleep, rate quality of your sleep (using Likert scale, ranged from 0 = very sound or restful, to 4 = very restless where lower score indicates better outcome). The primary purpose of the Waketime Questionnaire was to confirm anticipated reports of poor sleep. In this outcome measure, data for question "Time to fall asleep last night" has been reported.
Time frame: Day 1, Day 6
Part B: Change From Day 1 in Waketime Questionnaire Parameters: Number of Awakening After Falling Asleep at Day 6
Participants were asked to answer the following question using Waketime Questionnaire: How long did you sleep last night, number of awakening after falling asleep, time to fall asleep last night, time spent awake after falling asleep, rate quality of your sleep (using Likert scale, ranged from 0 = very sound or restful, to 4 = very restless where lower score indicates better outcome). The primary purpose of the Waketime Questionnaire was to confirm anticipated reports of poor sleep. In this outcome measure, data for question "Number of awakening after falling asleep" has been reported.
Time frame: Day 1, Day 6
Part B: Change From Day 1 in Waketime Questionnaire Parameters: Time Spent Awake After Falling Asleep at Day 6
Participants were asked to answer the following question using Waketime Questionnaire: How long did you sleep last night, number of awakening after falling asleep, time to fall asleep last night, time spent awake after falling asleep, rate quality of your sleep (using Likert scale, ranged from 0 = very sound or restful, to 4 = very restless where lower score indicates better outcome). The primary purpose of the Waketime Questionnaire was to confirm anticipated reports of poor sleep. In this outcome measure, data for question "Time spent awake after falling asleep" has been reported.
Time frame: Day 1, Day 6
Part B: Change From Day 1 in Waketime Questionnaire Parameters: Rate Quality of Your Sleep at Day 6
Participants were asked to answer the following question using Waketime Questionnaire: How long did you sleep last night, number of awakening after falling asleep, time to fall asleep last night, time spent awake after falling asleep, rate quality of your sleep (using Likert scale, ranged from 0 = very sound or restful, to 4 = very restless where lower score indicates better outcome). The primary purpose of the Waketime Questionnaire was to confirm anticipated reports of poor sleep. In this outcome measure, data for question "Rate quality of your sleep" has been reported.
Time frame: Day 1, Day 6
Part B: Change From Day 1 (Pre-dose) in Digit Symbol Substitution Test (DSST) Score at Day 6
DSST is a cognitive test designed to assess psychomotor speed of performance requiring visual perception, spatial decision-making, and motor skills. It consists of 133 digits and requires the participant to substitute each digit with a simple symbol in a 90-second period. Each correct symbol is counted, and the total score ranges from 0 (less than cognitive functioning) to 133 (greater than cognitive functioning) as a description of DSST. An increase in score represents an improvement in an integrated measure of cognitive function.
Time frame: Day 1 (Pre-dose), Day 6
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
PVT, a computer-based test, is a chronometric measure of an individual's reaction to specified small changes in a labile environment. Participants were instructed to respond to a digital signal on a computer terminal by pressing a key. Errors of omission and commission are recorded. When a participant did not respond to the PVT signal within 500 msec, it was termed a lapse. The higher the number of lapses the greater the impairment.
Time frame: Day 1 (Pre-dose), Day 6
Part B: Change From Day 1 (Pre-dose) in Score on Karolinska Sleepiness Scale (KSS) at Day 6
KSS is a 9-point scale, on which the participant has to mark his or her sleepiness during the previous 10 minutes. The scale ranges from 1, which indicates "extremely alert", to 9, which indicates "extremely sleepy, can't stay awake". Higher numbers indicating sleepier and lower numbers more alert.
Time frame: Day 1 (Pre-dose), Day 6
Part A: Maximum Plasma Concentration (Cmax) of E2006
Time frame: Day 1: Pre-dose, up to 240 hours post-dose
Part A: Time to Reach Maximum Plasma Concentration (Tmax) of E2006
Time frame: Day 1: Pre-dose, up to 240 hours post-dose
Part A: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC0-24) of E2006
Time frame: Day 1: Pre-dose, up to 240 hours post-dose
Part A: Area Under the Plasma Concentration-time Curve From Time Zero to t Hours (AUC0-t) of E2006
Time frame: Day 1: Pre-dose, up to 240 hours post-dose
Part A: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of E2006
Time frame: Day 1: Pre-dose, up to 240 hours post-dose
Part A: Terminal Half-life (t1/2) of E2006 in Plasma
Time frame: Day 1: Pre-dose, up to 240 hours post-dose
Part A: Apparent Total Clearance of E2006 From Plasma (CL/F)
Time frame: Day 1: Pre-dose, up to 240 hours post-dose
Part A: Apparent Volume of Distribution of E2006 in Plasma (Vz/F)
Time frame: Day 1: Pre-dose, up to 240 hours post-dose
Part A: Cumulative Amount of Unchanged Drug E2006 Excreted Into the Urine (Ae)
Time frame: Day 1: Pre-dose, up to 120 hours post-dose
Part A: Renal Clearance (CLR) of Drug E2006
Time frame: Day 1: Pre-dose, up to 120 hours post-dose
Part A: Maximum Change From Day 1 (Pre-dose) in Digit Symbol Substitution Test (DSST) Score at Day 6
DSST is a cognitive test designed to assess psychomotor speed of performance requiring visual perception, spatial decision-making, and motor skills. It consists of 133 digits and requires the participant to substitute each digit with a simple symbol in a 90-second period. Each correct symbol is counted, and the total score ranges from 0 (less than cognitive functioning) to 133 (greater than cognitive functioning) as a description of DSST. An increase in score represents an improvement in an integrated measure of cognitive function. In this outcome measure, data for participants who received placebo matched to "1 mg, 2.5 mg, 5 mg E2006" and matched to "10 mg, 25 mg, 50 mg, 100 mg, and 200 mg E2006", has been presented separately.
Time frame: Day 1 (Pre-dose), up to Day 6
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
PVT, a computer-based test, is a chronometric measure of an individual's reaction to specified small changes in a labile environment. Participants were instructed to respond to a digital signal on a computer terminal by pressing a key. Errors of omission and commission are recorded. When a participant did not respond to the PVT signal within 500 msec, it was termed a lapse. The higher the number of lapses the greater the impairment. In this outcome measure, data for participants who received placebo matched to "1 mg, 2.5 mg, 5 mg E2006" and matched to "10 mg, 25 mg, 50 mg, 100 mg, and 200 mg E2006", has been presented separately.
Time frame: Day 1 (Pre-dose), Day 6
Part A: Maximum Change From Day 1 (Pre-dose) in Karolinska Sleepiness Scale (KSS) Score at Day 6
KSS is a 9-point scale, on which the participant has to mark his or her sleepiness during the previous 10 minutes. The scale ranges from 1, which indicates "extremely alert", to 9, which indicates "extremely sleepy, can't stay awake". Higher numbers indicating sleepier and lower numbers more alert. In this outcome measure, data for participants who received placebo matched to "1 mg, 2.5 mg, 5 mg E2006" and matched to "10 mg, 25 mg, 50 mg, 100 mg, and 200 mg E2006", has been presented separately.
Time frame: Day 1 (Pre-dose), Day 6
Part A: Change From Day 1 in Waketime Questionnaire Parameters: How Long Did You Sleep Last Night at Day 6
Participants were asked to answer the following question using Waketime Questionnaire: How long did you sleep last night, number of awakening after falling asleep, time to fall asleep last night, time spent awake after falling asleep, rate quality of your sleep (using Likert scale, ranged from 0 = very sound or restful, to 4 = very restless where lower score indicates better outcome). The primary purpose of the Waketime Questionnaire was to confirm a lack of sleep disturbance. In this outcome measure, data for question "How long did you sleep last night" has been reported.
Time frame: Day 1, Day 6
Part A: Change From Day 1 in Waketime Questionnaire Parameters: Time to Fall Asleep Last Night at Day 6
Participants were asked to answer the following question using Waketime Questionnaire: How long did you sleep last night, number of awakening after falling asleep, time to fall asleep last night, time spent awake after falling asleep, rate quality of your sleep (using Likert scale, ranged from 0 = very sound or restful, to 4 = very restless where lower score indicates better outcome). The primary purpose of the Waketime Questionnaire was to confirm a lack of sleep disturbance. In this outcome measure, data for question "Time to fall asleep last night" has been reported.
Time frame: Day 1, Day 6
Part A: Change From Day 1 in Waketime Questionnaire Parameters: Number of Awakening After Falling Asleep at Day 6
Participants were asked to answer the following question using Waketime Questionnaire: How long did you sleep last night, number of awakening after falling asleep, time to fall asleep last night, time spent awake after falling asleep, rate quality of your sleep (using Likert scale, ranged from 0 = very sound or restful, to 4 = very restless where lower score indicates better outcome). The primary purpose of the Waketime Questionnaire was to confirm a lack of sleep disturbance. In this outcome measure, data for question "Number of awakening after falling asleep" has been reported.
Time frame: Day 1, Day 6
Part A: Change From Day 1 in Waketime Questionnaire Parameters: Time Spent Awake After Falling Asleep at Day 6
Participants were asked to answer the following question using Waketime Questionnaire: How long did you sleep last night, number of awakening after falling asleep, time to fall asleep last night, time spent awake after falling asleep, rate quality of your sleep (using Likert scale, ranged from 0 = very sound or restful, to 4 = very restless where lower score indicates better outcome). The primary purpose of the Waketime Questionnaire was to confirm a lack of sleep disturbance. In this outcome measure, data for question "Time spent awake after falling asleep" has been reported.
Time frame: Day 1, Day 6
Part A: Change From Day 1 in Waketime Questionnaire Parameters: Rate Quality of Your Sleep at Day 6
Participants were asked to answer the following question using Waketime Questionnaire: How long did you sleep last night, number of awakening after falling asleep, time to fall asleep last night, time spent awake after falling asleep, rate quality of your sleep (using Likert scale, ranged from 0 = very sound or restful, to 4 = very restless where lower score indicates better outcome). The primary purpose of the Waketime Questionnaire was to confirm a lack of sleep disturbance. In this outcome measure, data for question "Rate quality of your sleep" has been reported.
Time frame: Day 1, Day 6
Part B: Number of Participants With Treatment Emergent Adverse Events (AEs) and Treatment Emergent Serious Adverse Events (SAEs)
Time frame: Baseline up to Day 11
Part B: Number of Participants With Markedly Abnormal Laboratory Parameter Values
Time frame: Baseline up to Day 6
Part B: Number of Participants With Significant Change From Baseline in Vital Sign Values
Time frame: Baseline up to Day 11
Part B: Number of Participants With Clinically Significant Change From Baseline in ECG Parameter Values
Time frame: Baseline up to Day 11
Part B: Number of Participants With Any Suicidality Assessed Using Columbia-Suicide Severity Rating Scale (C-SSRS)
The C-SSRS (mapped to Columbia Classification Algorithm of Suicide Assessment \[C-CASA\]) is an interview-based rating scale to systematically assess any suicidality, any suicidal Behavior, any suicidal ideation. Any suicidality: emergence of any suicidal ideation or suicidal behavior. Any suicidal behavior: when response is "yes" for any these questions- actual attempt to suicide, engaged in non-suicidal self-injurious, behavior, interrupted attempt, aborted attempt, preparatory acts. Any suicidal ideation: when response is "yes" for any of these questions-wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent to suicide. Number of participants with any suicidality has been reported for this outcome measure.
Time frame: Baseline, Day 11