InsomniaPhase 1NCT01463098
A 2-Part Single Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of E2006
A Phase 1 study testing E2006 1.0 mg, E2006 2.5 mg and E2006 5.0 mg in people with Insomnia, run by Eisai Inc. at 2 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 64 yearsHealthy volunteers can take part
- Conditions the study is for
- Insomnia
- What is being tested?
- E2006 1.0 mg, E2006 2.5 mg and E2006 5.0 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 122 participants
- Where
- 2 sitesUnited States
- Study dates
- 5 Oct 2011to 11 Aug 2012
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 64 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Show all 11Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Community Research
Cincinnati, Ohio
Clinilabs, Inc.
New York, New York, 10019
About this study
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
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.
- Conditions
- Insomnia
- Being tested
- E2006 1.0 mg, E2006 2.5 mg, E2006 5.0 mg, E2006 10.0 mg, E2006 25.0 mg
- Medical subject headings
- Sleep Initiation and Maintenance Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
E2006 1.0 mgDrug
Also called Lemborexant
E2006 1.0 mg capsule.
E2006 2.5 mgDrug
Also called Lemborexant
E2006 2.5 mg capsule.
E2006 5.0 mgDrug
Also called Lemborexant
E2006 5.0 mg (2 capsules of 2.5 mg each).
E2006 10.0 mgDrug
Also called Lemborexant
E2006 10.0 mg capsule.
E2006 25.0 mgDrug
Also called Lemborexant
E2006 25.0 mg (2 capsules of 10 mg each and 2 capsules of 2.5 mg each).
E2006 50.0 mgDrug
Also called Lemborexant
E2006 50.0 mg capsule.
E2006 100 mgDrug
Also called Lemborexant
E2006 100 mg (2 capsules of 50 mg each).
E2006 200 mgDrug
Also called Lemborexant
E2006 200 mg (4 capsules of 50 mg each).
Zolpidem 10 mgDrug
Zolpidem 10 mg immediate release tablet.
E2006 Matched Placebo or Zolpidem Matched PlaceboDrug
E2006-matched placebo capsules or zolpidem-matched placebo tablets.
E2006 Matched PlaceboDrug
E2006-matched placebo capsule.
| Study group | Role | What they receive |
|---|---|---|
| Part A: E2006 1.0 mg | Experimental | Not described Receives: Drug: E2006 1.0 mg |
| Part A: E2006 2.5 mg | Experimental | Not described Receives: Drug: E2006 2.5 mg |
| Part A: E2006 5.0 mg | Experimental | Not described Receives: Drug: E2006 5.0 mg |
| Part A: E2006 10.0 mg | Experimental | Not described Receives: Drug: E2006 10.0 mg |
| Part A: E2006 25.0 mg | Experimental | Not described Receives: Drug: E2006 25.0 mg |
| Part A: E2006 50.0 mg | Experimental | Not described Receives: Drug: E2006 50.0 mg |
| Part A: E2006 100 mg | Experimental | Not described Receives: Drug: E2006 100 mg |
| Part A: E2006 200 mg | Experimental | Not described Receives: Drug: E2006 200 mg |
| Part B: Zolpidem 10 mg | Experimental | Not described Receives: Drug: Zolpidem 10 mg |
| Part B: E2006 Matched Placebo or Zolpidem Matched Placebo | Experimental | Not described Receives: Drug: E2006 Matched Placebo or Zolpidem Matched Placebo |
| Part A: E2006 Matched Placebo | Experimental | Not described Receives: Drug: E2006 Matched Placebo |
| Part B: E2006 2.5 mg | Experimental | Not described Receives: Drug: E2006 2.5 mg |
| Part B: E2006 10 mg | Experimental | Not described Receives: Drug: E2006 10.0 mg |
| Part B: E2006 25 mg | Experimental | Not described Receives: Drug: E2006 25.0 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A: Number of Participants With Treatment Emergent Adverse Events (AEs) and Treatment Emergent Serious Adverse Events (SAEs)
Measured: Baseline up to Day 11
Part A: Number of Participants With Markedly Abnormal Laboratory Parameter Values
Measured: Baseline up to Day 6
Part A: Number of Participants With Significant Change From Baseline in Vital Sign Values
Measured: Baseline up to Day 11
Part A: Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Parameter Values
Measured: 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.
Measured: 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.
Measured: Baseline, Day 1
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Day 1 (Pre-dose), Day 6
Secondary outcomes (23)
Part A: Maximum Plasma Concentration (Cmax) of E2006
Measured: Day 1: Pre-dose, up to 240 hours post-dose
Part A: Time to Reach Maximum Plasma Concentration (Tmax) of E2006
Measured: 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
Measured: 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
Measured: 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
Measured: Day 1: Pre-dose, up to 240 hours post-dose
Part A: Terminal Half-life (t1/2) of E2006 in Plasma
Measured: Day 1: Pre-dose, up to 240 hours post-dose
Part A: Apparent Total Clearance of E2006 From Plasma (CL/F)
Measured: Day 1: Pre-dose, up to 240 hours post-dose
Part A: Apparent Volume of Distribution of E2006 in Plasma (Vz/F)
Measured: Day 1: Pre-dose, up to 240 hours post-dose
Part A: Cumulative Amount of Unchanged Drug E2006 Excreted Into the Urine (Ae)
Measured: Day 1: Pre-dose, up to 120 hours post-dose
Part A: Renal Clearance (CLR) of Drug E2006
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Day 1, Day 6
Part B: Number of Participants With Treatment Emergent Adverse Events (AEs) and Treatment Emergent Serious Adverse Events (SAEs)
Measured: Baseline up to Day 11
Part B: Number of Participants With Markedly Abnormal Laboratory Parameter Values
Measured: Baseline up to Day 6
Part B: Number of Participants With Significant Change From Baseline in Vital Sign Values
Measured: Baseline up to Day 11
Part B: Number of Participants With Clinically Significant Change From Baseline in ECG Parameter Values
Measured: 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.
Measured: Baseline, Day 11
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2011 (estimated)
- Study start5 Oct 2011
- Primary completion11 Aug 2012
- Study completion11 Aug 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for InsomniaStudies of the same condition, open and under way.
- More trials run by Eisai Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 122 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eisai Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01463098
- Sponsor's protocol ID
- E2006-A001-001
- Status last verified
- Mar 2013
- First submitted
- 26 Oct 2011
- Last updated
- 18 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01463098
- Acronym / sponsor ID
- E2006-A001-001
- Conditions
- Insomnia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 122 participants (actual)
- Lead sponsor
- Eisai Inc.Industry (pharma, biotech, devices)
- Study start
- 5 Oct 2011 (actual)
- Primary completion
- 11 Aug 2012 (actual)
- Study completion
- 11 Aug 2012 (actual)
- First posted
- 1 Nov 2011 (estimated)
- Results
- Posted 18 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 14
| Arm | Type | Receives |
|---|---|---|
| Part A: E2006 1.0 mg | Experimental | Drug: E2006 1.0 mg |
| Part A: E2006 2.5 mg | Experimental | Drug: E2006 2.5 mg |
| Part A: E2006 5.0 mg | Experimental | Drug: E2006 5.0 mg |
| Part A: E2006 10.0 mg | Experimental | Drug: E2006 10.0 mg |
| Part A: E2006 25.0 mg | Experimental | Drug: E2006 25.0 mg |
| Part A: E2006 50.0 mg | Experimental | Drug: E2006 50.0 mg |
| Part A: E2006 100 mg | Experimental | Drug: E2006 100 mg |
| Part A: E2006 200 mg | Experimental | Drug: E2006 200 mg |
| Part B: Zolpidem 10 mg | Experimental | Drug: Zolpidem 10 mg |
| Part B: E2006 Matched Placebo or Zolpidem Matched Placebo | Experimental | Drug: E2006 Matched Placebo or Zolpidem Matched Placebo |
| Part A: E2006 Matched Placebo | Experimental | Drug: E2006 Matched Placebo |
| Part B: E2006 2.5 mg | Experimental | Drug: E2006 2.5 mg |
| Part B: E2006 10 mg | Experimental | Drug: E2006 10.0 mg |
| Part B: E2006 25 mg | Experimental | Drug: E2006 25.0 mg |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- 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
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| E2006 1.0 mgAlso: LemborexantE2006 1.0 mg capsule. | Drug | Part A: E2006 1.0 mg |
| E2006 2.5 mgAlso: LemborexantE2006 2.5 mg capsule. | Drug | Part A: E2006 2.5 mg, Part B: E2006 2.5 mg |
| E2006 5.0 mgAlso: LemborexantE2006 5.0 mg (2 capsules of 2.5 mg each). | Drug | Part A: E2006 5.0 mg |
| E2006 10.0 mgAlso: LemborexantE2006 10.0 mg capsule. | Drug | Part A: E2006 10.0 mg, Part B: E2006 10 mg |
| E2006 25.0 mgAlso: LemborexantE2006 25.0 mg (2 capsules of 10 mg each and 2 capsules of 2.5 mg each). | Drug | Part A: E2006 25.0 mg, Part B: E2006 25 mg |
| E2006 50.0 mgAlso: LemborexantE2006 50.0 mg capsule. | Drug | Part A: E2006 50.0 mg |
| E2006 100 mgAlso: LemborexantE2006 100 mg (2 capsules of 50 mg each). | Drug | Part A: E2006 100 mg |
| E2006 200 mgAlso: LemborexantE2006 200 mg (4 capsules of 50 mg each). | Drug | Part A: E2006 200 mg |
| Zolpidem 10 mgZolpidem 10 mg immediate release tablet. | Drug | Part B: Zolpidem 10 mg |
| E2006 Matched Placebo or Zolpidem Matched PlaceboE2006-matched placebo capsules or zolpidem-matched placebo tablets. | Drug | Part B: E2006 Matched Placebo or Zolpidem Matched Placebo |
| E2006 Matched PlaceboE2006-matched placebo capsule. | Drug | Part A: E2006 Matched Placebo |
Primary outcome
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)
Time frame: Baseline, Day 11
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.
Part B: Change From Baseline in Latency to Persistent Sleep (LPS) Assessed Using Polysomnography (PSG) Measurement at Day 1
Time frame: Baseline, 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.
Part B: Change From Baseline in Total Sleep Time (TST) Assessed Using PSG at Day 1
Time frame: Baseline, 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.
Part B: Change From Baseline in Sleep Efficiency Assessed Using PSG at Day 1
Time frame: Baseline, 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.
Part B: Change From Baseline in Wake After Sleep Onset (WASO) Assessed Using PSG at Day 1
Time frame: Baseline, Day 1
WASO was defined as the duration (in minutes) of wakefulness from onset of persistent sleep to lights-on.
Part B: Change From Baseline in Number of Awakenings After Persistent Sleep (NAW) Assessed Using PSG at Day 1
Time frame: Baseline, 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.
Part B: Change From Baseline in Percentage of Each Sleep Stage Duration Assessed Using PSG at Day 1
Time frame: Baseline, 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.
Part B: Change From Baseline in Duration (in Minutes) of Each Sleep Stage Assessed Using PSG at Day 1
Time frame: Baseline, 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.
Part B: Change From Baseline in Mean Total Number of Shift in Sleep Stages Assessed Using PSG at Day 1
Time frame: Baseline, 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.
Part B: Change From Day 1 in Waketime Questionnaire Parameters: How Long Did You Sleep Last Night at Day 6
Time frame: Day 1, 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.
Part B: Change From Day 1 in Waketime Questionnaire Parameters: Time to Fall Asleep Last Night at Day 6
Time frame: Day 1, 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.
Part B: Change From Day 1 in Waketime Questionnaire Parameters: Number of Awakening After Falling Asleep at Day 6
Time frame: Day 1, 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.
Part B: Change From Day 1 in Waketime Questionnaire Parameters: Time Spent Awake After Falling Asleep at Day 6
Time frame: Day 1, 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.
Part B: Change From Day 1 in Waketime Questionnaire Parameters: Rate Quality of Your Sleep at Day 6
Time frame: Day 1, 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.
Part B: Change From Day 1 (Pre-dose) in Digit Symbol Substitution Test (DSST) Score at Day 6
Time frame: Day 1 (Pre-dose), 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.
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
Time frame: Day 1 (Pre-dose), 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.
Part B: Change From Day 1 (Pre-dose) in Score on Karolinska Sleepiness Scale (KSS) at Day 6
Time frame: Day 1 (Pre-dose), 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.
23 secondary outcomes
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
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
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
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
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
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
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
Time frame: Day 1, Day 6
Part A: Change From Day 1 in Waketime Questionnaire Parameters: Rate Quality of Your Sleep at Day 6
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)
Time frame: Baseline, Day 11
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing E2006 1.0 mg, E2006 2.5 mg and E2006 5.0 mg in people with Insomnia, run by Eisai Inc. at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 21 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2020.