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Study of Lemborexant for Irregular Sleep-Wake Rhythm Disorder and Mild to Moderate Alzheimer's Disease Dementia

Primary Purpose

Irregular Sleep-Wake Rhythm Disorder

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Lemborexant 2.5 mg

Lemborexant 5 mg

Lemborexant 10 mg

Lemborexant 15 mg

Lemborexant-matched placebo

About this trial

This is an interventional treatment trial for Irregular Sleep-Wake Rhythm Disorder focused on measuring Mild to Moderate Alzheimer's Disease Dementia, sleep, circadian rhythms

Eligibility Criteria

60 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria (Core Study):

Male or female, age 60 to 90 years at the time of informed consent
Able to provide informed consent. If a participant lacks capacity to consent in the investigator's opinion, the participant's assent should be obtained, if required in accordance with local laws, regulations and customs, and the written informed consent of a legal representative should be obtained (capacity to consent and definition of legal representative should be determined in accordance with applicable local laws and regulations).
Documentation of diagnosis with Alzheimer's disease dementia (AD-D) on the basis of the National Institute on Aging/Alzheimer's Association Diagnostic Guidelines
Mini Mental State Examination 10 to 26 at Screening
Meets criteria for Circadian Rhythm Sleep Disorder, Irregular Sleep-Wake Type (Diagnostic and Statistical Manual of Mental Disorders - 5th edition) and the 10th revision of the International Classification of Diseases, as follows: Complaint by the participant or caregiver of difficulty sleeping during the night and/or excessive daytime sleepiness associated with multiple irregular sleep bouts during a 24-hour period
Frequency of complaint of sleep and wake fragmentation ≥3 days per week
Duration of complaint of sleep and wake fragmentation ≥3 months
During the Screening Period, mean actigraphy-derived sleep efficiency (aSE) <87.5% within the defined nocturnal sleep period and mean actigraphy-derived wake efficiency (aWE) <87.5% during the defined wake period
Confirmation by actigraphy of a combination of sleep bouts of >10 minutes during the wake period plus wake bouts of >10 minutes during the sleep period, totaling at least 4 bouts per 24 hours period, ≥ 3 days per week
Ambulatory and living in the community or in a residence not classified as a skilled nursing facility (an assisted living facility with separate living quarters where participants and their caregivers reside is acceptable)
Willing not to start a behavioral or other treatment program for sleep or wake difficulties and not to start a new treatment for other symptoms of AD-D during participation in the study
Has a reliable and competent caregiver (or caregiver and informants) who can accompany the participant to study visits, administer study medication on a nightly basis and provide information on the status of the participant
For participants taking a cholinesterase inhibitor and/or memantine, dosing regimen must have been stable for at least 3 months

Inclusion Criteria (Extension Phase):

Completed the Core Study (End of Study [EOS] Visit). Participants who participated in the Core Study and completed the EOS Visit within 30 days may return to participate in the Extension Phase as long as there are no contraindications due to ongoing adverse events or prohibited medications.

Inclusion Criteria for Caregivers:

Able to provide informed consent
Spends at least 10 hours per week with the participant
Able to meet caregiver requirements
Willing to provide information on himself/herself regarding sleep quality and caregiver Burden

Exclusion Criteria:

A diagnosis of vascular dementia, dementia following multiple strokes, or any synucleinopathy / Lewy body disorder. This includes Dementia with Lewy Bodies and Parkinson's disease with or without dementia.
A current diagnosis of moderate to severe obstructive sleep apnea (OSA) or central sleep apnea, or current use of continuous positive airways pressure even if mild severity of OSA, restless legs syndrome, periodic limb movement disorder (with awakenings), or narcolepsy
An Apnea-Hypopnea Index or equivalent ≥15 events/hour on diagnostic sleep study conducted prior to Baseline or within 6 months of Screening
A clinically significant movement disorder that would affect the differentiation of sleep and wake by the actigraphy analytic algorithm
Current symptoms or history during the past year of Rapid Eye Movement Behavior Disorder or sleep-related violent behavior
Probable Major Depression, as evidenced by score >10 on the Cornell Scale for Depression in Dementia at Screening
Unable to tolerate wearing the actigraph. At a minimum, participants must be able to wear the actigraph for 5 complete days out of 7 days' data. A day will be considered complete as long as data from 90% of the 24-hour period are able to be scored.
Excessive caffeine use that in the opinion of the investigator contributes to the participant's Irregular Sleep-Wake Rhythm Disorder (ISWRD)
History of drug or alcohol dependency or abuse within approximately the previous 2 years
Reports habitually consuming more than 14 drinks containing alcohol per week or habitually consumes alcohol within 3 hours before bedtime and unwilling to limit alcohol intake to 2 or fewer drinks per day or forego having alcohol within 3 hours before bedtime for the duration of his/her participation in the study
Known to be human immunodeficiency virus positive
Active viral hepatitis (B or C) as demonstrated by positive serology at Screening
A prolonged QTcF interval (QTcF >450 milliseconds[ms]) as demonstrated by a repeated electrocardiogram (ECG) at Screening (repeated only if initial ECG indicates a QTcF interval >450 ms) (participants with evidence of bundle branch block are not excluded if the block is not clinically significant, as documented by the investigator in the source document)
Current evidence of clinically significant disease that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments
Any history of a medical or psychiatric condition other than Alzheimer's Disease dementia that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments
History of malignancy within the previous 5 years except for adequately treated basal cell or squamous cell skin cancer or cervical carcinoma in situ
Any suicidal ideation with intent with or without a plan, at the time of or within 6 months of Screening, as indicated by answering "Yes" to questions 4 and 5 on the Suicidal Ideation section of the electronic version of the Columbia Suicide Severity Rating Scale (eC-SSRS)
Any suicidal behavior within the past 10 years based on the eC-SSRS
History of violence toward the caregiver or others
Scheduled for surgery using general anesthesia during the study
Used any prohibited prescription or over-the-counter concomitant medications within 1 week or 5 half-lives, whichever is longer, before starting actigraphy during Screening
Used any modality of treatment for ISWRD between Screening and Randomization based on approaches related to circadian rhythms, including phototherapy (light therapy), melatonin and melatonin agonists
Failed treatment with Belsomra (efficacy and/or safety) following treatment with an appropriate dose and of adequate duration in the opinion of the investigator
Transmeridian travel across more than 3 time zones between Screening and Randomization, or plans to travel across more than 3 time zones during the study
Hypersensitivity to lemborexant or to its excipients
Currently enrolled in another clinical trial, except for observational studies with no treatment component
Used any investigational drug or device before informed consent (ie, within 30 days or 5× the investigational drug half-life whichever is longer or 6 months for potential disease-modifying drugs)
Previously participated in any clinical trial of lemborexant

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Placebo Comparator

Arm Label

Lemborexant 2.5 milligrams (mg)

Lemborexant 5 mg

Lemborexant 10 mg

Lemborexant 15 mg

Lemborexant-matched placebo

Arm Description

Participants will take one lemborexant 2.5 mg tablet and one lemborexant-matched placebo tablet orally each night for 28 consecutive nights immediately (i.e., within 5 minutes) before the time the participant intends to try to sleep.

Participants will take one lemborexant 5 mg tablet and one lemborexant-matched placebo tablet orally each night for 28 consecutive nights immediately (i.e., within 5 minutes) before the time the participant intends to try to sleep.

Participants will take one lemborexant 10 mg tablet and one lemborexant-matched placebo tablet orally each night for 28 consecutive nights immediately (i.e., within 5 minutes) before the time the participant intends to try to sleep.

Participants will take one lemborexant 5 mg tablet and one lemborexant 10 mg tablet orally each night for 28 consecutive nights immediately (i.e., within 5 minutes) before the time the participant intends to try to sleep.

Participants will take two lemborexant-matched placebo tablets orally each night for 28 consecutive nights immediately (i.e., within 5 minutes) before the time the participant intends to try to sleep.

Outcomes

Primary Outcome Measures

Core Phase: Change From Baseline in Mean Actigraphy Sleep Efficiency (aSE) With Lemborexant Compared to Placebo During Week 1 of Treatment

aSE was defined as the percentage of time spent in bed nocturnal sleeping, as measured by actigraphy. Sleep efficiency was calculated as the total duration of sleep epochs during the predefined 8-hour nocturnal sleep period divided by 8 hours and multiplied by 100. Higher values were better. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average first 7 nights of treatment was reported.

Core Phase: Change From Baseline in Mean aSE With Lemborexant Compared to Placebo During Week 2 of Treatment

Core Phase: Change From Baseline in Mean aSE With Lemborexant Compared to Placebo During Week 3 of Treatment

Core Phase: Change From Baseline in Mean aSE With Lemborexant Compared to Placebo During Week 4 of Treatment

Core Phase: Change From Baseline in Mean Sleep Fragmentation Index (SFI) During Week 1 of Treatment

The SFI was defined as the sum of a movement index (MI) and a fragmentation index (FI) during the logged sleep period. The MI was equal to the epochs of wake per time in bed (TBI) multiplied by 100. The FI was equal to the number of less than or equal to (<=) 1-minute periods of immobility/total number of periods of immobility of all durations during the defined nocturnal sleep period multiplied by 100. Value ranges from 0-100 percent (%) (lower values were better). SFI was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average first 7 nights of treatment was reported.

Core Phase: Change From Baseline in Mean SFI During Week 2 of Treatment

The SFI was defined as the sum of a MI and a FI during the logged sleep period. The MI was equal to the epochs of wake per TBI multiplied by 100. The FI was equal to the number <=1-minute periods of immobility/total number of periods of immobility of all durations during the defined nocturnal sleep period multiplied by 100. Value ranges from 0-100% (lower values were better). SFI was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average second 7 nights of treatment was reported.

Core Phase: Change From Baseline in Mean SFI During Week 3 of Treatment

Core Phase: Change From Baseline in Mean SFI During Week 4 of Treatment

Core Phase: Change From Baseline in the Mean Duration of Wake Bouts (aMeanDurWB) During Week 1 of Treatment

aMeanDurWB was defined as an average duration of all wake bouts that occurred during the defined nocturnal predefined sleep period. The wake bout was defined as continuous wake of 10 minutes or longer. Lower values were better. aMeanDurWB was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average first 7 nights of treatment was reported.

Core Phase: Change From Baseline in the aMeanDurWB During Week 2 of Treatment

Core Phase: Change From Baseline in the aMeanDurWB During Week 3 of Treatment

Core Phase: Change From Baseline in the aMeanDurWB During Week 4 of Treatment

Core Phase: Change From Baseline in Mean Actigraphy Wake Efficiency (aWE) During Week 1 of Treatment

aWE was defined as the percentage of time spent awake in bed during defined wake period, as measured by actigraphy. Wake efficiency was calculated as the total duration of wake epochs during 16 hours outside of the predefined sleep period divided by 16 hours and multiplied by 100. Higher values were better. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average first 7 nights of treatment was reported.

Core Phase: Change From Baseline in Mean aWE During Week 2 of Treatment

Core Phase: Change From Baseline in Mean aWE During Week 3 of Treatment

Core Phase: Change From Baseline in Mean aWE During Week 4 of Treatment

Core Phase: Change From Baseline in Mean Wake Fragmentation Index (WFI) During Week 1 of Treatment

The WFI were calculated as the sum of an immobility index (II) and a FI during the logged wake period. The II was equal to the epochs of immobility per the 16 hours outside of the defined sleep period multiplied by 100. The FI was equal to the number of <=1-minute periods of mobility/total number of periods of mobility the 16 hours outside of the defined sleep period multiplied by 100. Value ranges from 0-100 percent (lower values were better). The WFI was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average first 7 nights of treatment was reported.

Core Phase: Change From Baseline in Mean WFI During Week 2 of Treatment

The WFI were calculated as the sum of an II and a FI during the logged wake period. The II was equal to the epochs of immobility per the 16 hours outside of the defined sleep period multiplied by 100. The FI was equal to the number of <=1-minute periods of mobility/total number of periods of mobility the 16 hours outside of the defined sleep period multiplied by 100. Value ranges from 0-100% (lower values were better). The WFI was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average second 7 nights of treatment was reported.

Core Phase: Change From Baseline in Mean WFI During Week 3 of Treatment

Core Phase: Change From Baseline in Mean WFI During Week 4 of Treatment

Core Phase: Change From Baseline in the Mean Duration of Sleep Bouts (aMeanDurSB) During Week 1 of Treatment

aMeanDurSB was defined as an average duration of all sleep bouts that occurred during the 16 hours outside of the predefined nocturnal sleep period. The sleep bout was defined as the continuous sleep of 10 minutes or longer. Lower values were better. aMeanDurSB was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average first 7 nights of treatment was reported.

Core Phase: Change From Baseline in the aMeanDurSB During Week 2 of Treatment

Core Phase: Change From Baseline in the aMeanDurSB During Week 3 of Treatment

Core Phase: Change From Baseline in the aMeanDurSB During Week 4 of Treatment

Core Phase: Change From Baseline in Mean Intradaily Variability Over Week 1 of Treatment

Intradaily variability gives an indication of irregular sleep-wake rhythm disorder (ISWRD) by quantifying the number and strength of transitions between rest and activity bouts, derived by the ratio of the mean squares of the difference between all successive hours (first derivative) and the mean squares around the grand mean (overall variance). The variable has a theoretical range of 0 to 2, with higher values indicating higher fragmentation. Intradaily variability was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average first 7 nights of treatment was reported.

Core Phase: Change From Baseline in Mean Intradaily Variability Over Week 2 of Treatment

Intradaily variability gives an indication of ISWRD by quantifying the number and strength of transitions between rest and activity bouts, derived by the ratio of the mean squares of the difference between all successive hours (first derivative) and the mean squares around the grand mean (overall variance). The variable has a theoretical range of 0 to 2, with higher values indicating higher fragmentation. Intradaily variability was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average second 7 nights of treatment was reported.

Core Phase: Change From Baseline in Mean Intradaily Variability Over Week 3 of Treatment

Core Phase: Change From Baseline in Mean Intradaily Variability Over Week 4 of Treatment

Core Phase: Change From Baseline in Mean Interdaily Stability (IS) Over Week 1 of Treatment

IS gives an indication of the stability of the sleep-wake rhythm across days, and varies from zero (low stability) to 1 (high stability). IS was derived by the ratio between the variance of the average 24-hour pattern around the mean and the overall variance. Higher values indicated stable rhythm. IS was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average first 7 nights of treatment was reported.

Core Phase: Change From Baseline in Mean IS Over Week 2 of Treatment

Core Phase: Change From Baseline in Mean IS Over Week 3 of Treatment

Core Phase: Change From Baseline in Mean IS Over Week 4 of Treatment

Core Phase: Change From Baseline in Average Activity Counts Across Least Active 5-hour Period (L5) Per 24-Hour Period Over Week 1 of Treatment

L5 was defined as the average activity across the least active 5-hour period per 24-hour period, with high values indicating restlessness. This value provides an indication of how restful (inactive) and regular the sleep periods are. L5 was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average first 7 nights of treatment was reported.

Core Phase: Change From Baseline in Average Activity Counts Across L5 Per 24-Hour Period Over Week 2 of Treatment

Core Phase: Change From Baseline in Average Activity Counts Across L5 Per 24-Hour Period Over Week 3 of Treatment

Core Phase: Change From Baseline in Average Activity Counts Across L5 Per 24-Hour Period Over Week 4 of Treatment

Core Phase: Change From Baseline in the Average Activity Count During the Most Active 10-hour Period (M10) Per 24-Hour Period Over Week 1 of Treatment

M10 was defined as the average activity during the most active 10-hour period per 24-hour period with low levels indicating inactivity. M10 was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average first 7 nights of treatment was reported.

Core Phase: Change From Baseline in the Average Activity Count During the M10 Per 24-Hour Period Over Week 2 of Treatment

Core Phase: Change From Baseline in the Average Activity Count During the M10 Per 24-Hour Period Over Week 3 of Treatment

Core Phase: Change From Baseline in the Average Activity Count During the M10 Per 24-Hour Period Over Week 4 of Treatment

Core Phase: Change From Baseline in Amplitude of the Rest-activity Rhythm (AMP) Over Week 1 of Treatment

AMP was amplitude of rest-activity rhythm calculated as the difference between M10 and L5. L5 was defined as the average activity across the least active 5-hour period per 24-hour period, with high values indicating restlessness. M10 was defined as the average activity during the most active 10-hour period per 24-hour period with low levels indicating inactivity. AMP was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average first 7 nights of treatment was reported.

Core Phase: Change From Baseline in AMP Over Week 2 of Treatment

Core Phase: Change From Baseline in AMP Over Week 3 of Treatment

Core Phase: Change From Baseline in AMP Over Week 4 of Treatment

Core Phase: Change From Baseline in Relative Amplitude in the Rest-activity Rhythm (RA) Over Week 1 of Treatment

RA was relative amplitude of the rest-activity rhythm calculated as the difference between M10 and L5 divided by M10 plus L5. L5 was defined as the average activity across the least active 5-hour period per 24-hour period, with high values indicating restlessness. M10 was defined as the average activity during the most active 10-hour period per 24-hour period with low levels indicating inactivity. RA was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average first 7 nights of treatment was reported.

Core Phase: Change From Baseline in RA Over Week 2 of Treatment

Core Phase: Change From Baseline in RA Over Week 3 of Treatment

Core Phase: Change From Baseline in RA Over Week 4 of Treatment

Secondary Outcome Measures

Full Information

NCT ID

NCT03001557

First Posted

November 16, 2016

Last Updated

April 14, 2021

Sponsor

Eisai Inc.

Collaborators

Purdue Pharma LP

1. Study Identification

Unique Protocol Identification Number

NCT03001557

Brief Title

Study of Lemborexant for Irregular Sleep-Wake Rhythm Disorder and Mild to Moderate Alzheimer's Disease Dementia

Official Title

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study With Open-Label Extension Phase of the Efficacy and Safety of Lemborexant in Subjects With Irregular Sleep-Wake Rhythm Disorder and Mild to Moderate Alzheimer's Disease Dementia

Study Type

Interventional

2. Study Status

Record Verification Date

April 2021

Overall Recruitment Status

Completed

Study Start Date

December 20, 2016 (Actual)

Primary Completion Date

July 26, 2018 (Actual)

Study Completion Date

April 17, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eisai Inc.

Collaborators

Purdue Pharma LP

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This study will be conducted to determine the dose response of lemborexant (LEM) on the change from baseline in actigraphy-derived sleep-related parameters, wake-related parameters, and circadian-rhythm related parameters. Following the eligibility screening period, eligible participants will be assigned at random to 1 of 4 doses of LEM or to placebo for 4 weeks. After a 2-week follow-up period, eligible participants may enter an open-label extension period for up to 30 months or until the program discontinuation.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Irregular Sleep-Wake Rhythm Disorder

Keywords

Mild to Moderate Alzheimer's Disease Dementia, sleep, circadian rhythms

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

63 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Lemborexant 2.5 milligrams (mg)

Arm Type

Experimental

Arm Description

Arm Title

Lemborexant 5 mg

Arm Type

Experimental

Arm Description

Arm Title

Lemborexant 10 mg

Arm Type

Experimental

Arm Description

Arm Title

Lemborexant 15 mg

Arm Type

Experimental

Arm Description

Arm Title

Lemborexant-matched placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Lemborexant 2.5 mg

Intervention Description

Lemborexant 2.5 mg tablets

Intervention Type

Drug

Intervention Name(s)

Lemborexant 5 mg

Intervention Description

Lemborexant 5 mg tablets

Intervention Type

Drug

Intervention Name(s)

Lemborexant 10 mg

Intervention Description

Lemborexant 10 mg tablets

Intervention Type

Drug

Intervention Name(s)

Lemborexant 15 mg

Intervention Description

Lemborexant 5 mg and 10 mg tablets

Intervention Type

Drug

Intervention Name(s)

Lemborexant-matched placebo

Intervention Description

Lemborexant-matched placebo tablets

Primary Outcome Measure Information:

Title

Core Phase: Change From Baseline in Mean Actigraphy Sleep Efficiency (aSE) With Lemborexant Compared to Placebo During Week 1 of Treatment

Description

Time Frame

Baseline, Week 1

Title

Core Phase: Change From Baseline in Mean aSE With Lemborexant Compared to Placebo During Week 2 of Treatment

Description

Time Frame

Baseline, Week 2

Title

Core Phase: Change From Baseline in Mean aSE With Lemborexant Compared to Placebo During Week 3 of Treatment

Description

Time Frame

Baseline, Week 3

Title

Core Phase: Change From Baseline in Mean aSE With Lemborexant Compared to Placebo During Week 4 of Treatment

Description

Time Frame

Baseline, Week 4

Title

Core Phase: Change From Baseline in Mean Sleep Fragmentation Index (SFI) During Week 1 of Treatment

Description

Time Frame

Baseline, Week 1

Title

Core Phase: Change From Baseline in Mean SFI During Week 2 of Treatment

Description

Time Frame

Baseline, Week 2

Title

Core Phase: Change From Baseline in Mean SFI During Week 3 of Treatment

Description

Time Frame

Baseline, Week 3

Title

Core Phase: Change From Baseline in Mean SFI During Week 4 of Treatment

Description

Time Frame

Baseline, Week 4

Title

Core Phase: Change From Baseline in the Mean Duration of Wake Bouts (aMeanDurWB) During Week 1 of Treatment

Description

Time Frame

Baseline, Week 1

Title

Core Phase: Change From Baseline in the aMeanDurWB During Week 2 of Treatment

Description

Time Frame

Baseline, Week 2

Title

Core Phase: Change From Baseline in the aMeanDurWB During Week 3 of Treatment

Description

Time Frame

Baseline, Week 3

Title

Core Phase: Change From Baseline in the aMeanDurWB During Week 4 of Treatment

Description

Time Frame

Baseline, Week 4

Title

Core Phase: Change From Baseline in Mean Actigraphy Wake Efficiency (aWE) During Week 1 of Treatment

Description

Time Frame

Baseline, Week 1

Title

Core Phase: Change From Baseline in Mean aWE During Week 2 of Treatment

Description

Time Frame

Baseline, Week 2

Title

Core Phase: Change From Baseline in Mean aWE During Week 3 of Treatment

Description

Time Frame

Baseline, Week 3

Title

Core Phase: Change From Baseline in Mean aWE During Week 4 of Treatment

Description

Time Frame

Baseline, Week 4

Title

Core Phase: Change From Baseline in Mean Wake Fragmentation Index (WFI) During Week 1 of Treatment

Description

Time Frame

Baseline, Week 1

Title

Core Phase: Change From Baseline in Mean WFI During Week 2 of Treatment

Description

Time Frame

Baseline, Week 2

Title

Core Phase: Change From Baseline in Mean WFI During Week 3 of Treatment

Description

Time Frame

Baseline, Week 3

Title

Core Phase: Change From Baseline in Mean WFI During Week 4 of Treatment

Description

Time Frame

Baseline, Week 4

Title

Core Phase: Change From Baseline in the Mean Duration of Sleep Bouts (aMeanDurSB) During Week 1 of Treatment

Description

Time Frame

Baseline, Week 1

Title

Core Phase: Change From Baseline in the aMeanDurSB During Week 2 of Treatment

Description

Time Frame

Baseline, Week 2

Title

Core Phase: Change From Baseline in the aMeanDurSB During Week 3 of Treatment

Description

Time Frame

Baseline, Week 3

Title

Core Phase: Change From Baseline in the aMeanDurSB During Week 4 of Treatment

Description

Time Frame

Baseline, Week 4

Title

Core Phase: Change From Baseline in Mean Intradaily Variability Over Week 1 of Treatment

Description

Time Frame

Baseline, Week 1

Title

Core Phase: Change From Baseline in Mean Intradaily Variability Over Week 2 of Treatment

Description

Time Frame

Baseline, Week 2

Title

Core Phase: Change From Baseline in Mean Intradaily Variability Over Week 3 of Treatment

Description

Time Frame

Baseline, Week 3

Title

Core Phase: Change From Baseline in Mean Intradaily Variability Over Week 4 of Treatment

Description

Time Frame

Baseline, Week 4

Title

Core Phase: Change From Baseline in Mean Interdaily Stability (IS) Over Week 1 of Treatment

Description

Time Frame

Baseline, Week 1

Title

Core Phase: Change From Baseline in Mean IS Over Week 2 of Treatment

Description

Time Frame

Baseline, Week 2

Title

Core Phase: Change From Baseline in Mean IS Over Week 3 of Treatment

Description

Time Frame

Baseline, Week 3

Title

Core Phase: Change From Baseline in Mean IS Over Week 4 of Treatment

Description

Time Frame

Baseline, Week 4

Title

Core Phase: Change From Baseline in Average Activity Counts Across Least Active 5-hour Period (L5) Per 24-Hour Period Over Week 1 of Treatment

Description

Time Frame

Baseline, Week 1

Title

Core Phase: Change From Baseline in Average Activity Counts Across L5 Per 24-Hour Period Over Week 2 of Treatment

Description

Time Frame

Baseline, Week 2

Title

Core Phase: Change From Baseline in Average Activity Counts Across L5 Per 24-Hour Period Over Week 3 of Treatment

Description

Time Frame

Baseline, Week 3

Title

Core Phase: Change From Baseline in Average Activity Counts Across L5 Per 24-Hour Period Over Week 4 of Treatment

Description

Time Frame

Baseline, Week 4

Title

Core Phase: Change From Baseline in the Average Activity Count During the Most Active 10-hour Period (M10) Per 24-Hour Period Over Week 1 of Treatment

Description

Time Frame

Baseline, Week 1

Title

Core Phase: Change From Baseline in the Average Activity Count During the M10 Per 24-Hour Period Over Week 2 of Treatment

Description

Time Frame

Baseline, Week 2

Title

Core Phase: Change From Baseline in the Average Activity Count During the M10 Per 24-Hour Period Over Week 3 of Treatment

Description

Time Frame

Baseline, Week 3

Title

Core Phase: Change From Baseline in the Average Activity Count During the M10 Per 24-Hour Period Over Week 4 of Treatment

Description

Time Frame

Baseline, Week 4

Title

Core Phase: Change From Baseline in Amplitude of the Rest-activity Rhythm (AMP) Over Week 1 of Treatment

Description

Time Frame

Baseline, Week 1

Title

Core Phase: Change From Baseline in AMP Over Week 2 of Treatment

Description

Time Frame

Baseline, Week 2

Title

Core Phase: Change From Baseline in AMP Over Week 3 of Treatment

Description

Time Frame

Baseline, Week 3

Title

Core Phase: Change From Baseline in AMP Over Week 4 of Treatment

Description

Time Frame

Baseline, Week 4

Title

Core Phase: Change From Baseline in Relative Amplitude in the Rest-activity Rhythm (RA) Over Week 1 of Treatment

Description

Time Frame

Baseline, Week 1

Title

Core Phase: Change From Baseline in RA Over Week 2 of Treatment

Description

Time Frame

Baseline, Week 2

Title

Core Phase: Change From Baseline in RA Over Week 3 of Treatment

Description

Time Frame

Baseline, Week 3

Title

Core Phase: Change From Baseline in RA Over Week 4 of Treatment

Description

Time Frame

Baseline, Week 4

Other Pre-specified Outcome Measures:

Title

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Time Frame

First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)

Title

Core Phase: Number of Participants in Each Category With Clinician's Global Impression of Change-Irregular Sleep-Wake Rhythm Disorder (CGIC-ISWRD) Global Score at Day 29

Description

The CGIC-ISWRD scale is a validated categorical measure of change in the participant's clinical condition between baseline and follow-up visits. It relies on both direct examination of the participant and an interview of the informant. The instrument consisted of 3 parts: a guided baseline interview administered to the participant and an informant, a follow-up interview administered to the participant and an informant, and a clinician's rating review. The baseline interview served as a reference for future ratings. During the baseline interview, the rater evaluated participant regarding domains of (1) sleep and wake symptoms; (2) mood and behavioral symptoms; (3) attention/arousal; and (4) social functioning. In the follow-up interview, a 7-pointscale was used, from 1 = marked improvement, 4 = no change, to 7 = marked worsening, to score each of the 4 domains and to provide a global score (1 [marked improvement] to 7 [marked worsening]).

Time Frame

Day 29

Title

Core Phase: Change From Baseline in the Neuropsychiatric Inventory (NPI-10) Total Score at Day 29

Description

The NPI-10 assessed a wide range of behaviors seen in dementia for both frequency and severity. It is a 10 item questionnaire with the following domains: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/liability and aberrant motor behavior. The total score was summarized and analyzed. This scale was administered with the caregiver as proxy for the participant. The total score was a sum of the 10 domains, where the score of each domain was calculated as frequency (scale: 1=occasionally to 4=very frequently) * Severity (scale: 1=Mild to 3=Severe). Each domain has a maximum score of 12 and all domains were equally weighted for total score, thus the range for the total score is 0 to 120 with 0 being completely healthy to 120 which is the worse score participant could get.

Time Frame

Baseline, Day 29

Title

Core Phase: Change From Baseline in the Sleep Disorders Inventory (SDI) Score at Day 29

Description

The SDI is an expanded version of one item of the NPI. It described the frequency, severity, and caregiver burden of sleep-disturbed behaviors during a period prior to its administration. The SDI consists of the 7 sub questions relating to sleep from the NPI sleep disturbance item. Each of the sub questions is a separate question with frequency, severity, and caregiver distress rated by the caregiver with respect to the patient-participant for the 2 weeks prior to the visit. The SDI score is derived as the product of the average of the frequency ratings and the average of the severity ratings (range: 0-12 [worst]).

Time Frame

Baseline, Day 29

Title

Extension Phase: Change From Baseline in SDI Total Score.

Description

Time Frame

Baseline, Day 133, 223, 313, 343, 373, 403, 493, 583, 673, and 763

10. Eligibility

Sex

All

Minimum Age & Unit of Time

60 Years

Maximum Age & Unit of Time

90 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria (Core Study): Male or female, age 60 to 90 years at the time of informed consent Able to provide informed consent. If a participant lacks capacity to consent in the investigator's opinion, the participant's assent should be obtained, if required in accordance with local laws, regulations and customs, and the written informed consent of a legal representative should be obtained (capacity to consent and definition of legal representative should be determined in accordance with applicable local laws and regulations). Documentation of diagnosis with Alzheimer's disease dementia (AD-D) on the basis of the National Institute on Aging/Alzheimer's Association Diagnostic Guidelines Mini Mental State Examination 10 to 26 at Screening Meets criteria for Circadian Rhythm Sleep Disorder, Irregular Sleep-Wake Type (Diagnostic and Statistical Manual of Mental Disorders - 5th edition) and the 10th revision of the International Classification of Diseases, as follows: Complaint by the participant or caregiver of difficulty sleeping during the night and/or excessive daytime sleepiness associated with multiple irregular sleep bouts during a 24-hour period Frequency of complaint of sleep and wake fragmentation ≥3 days per week Duration of complaint of sleep and wake fragmentation ≥3 months During the Screening Period, mean actigraphy-derived sleep efficiency (aSE) <87.5% within the defined nocturnal sleep period and mean actigraphy-derived wake efficiency (aWE) <87.5% during the defined wake period Confirmation by actigraphy of a combination of sleep bouts of >10 minutes during the wake period plus wake bouts of >10 minutes during the sleep period, totaling at least 4 bouts per 24 hours period, ≥ 3 days per week Ambulatory and living in the community or in a residence not classified as a skilled nursing facility (an assisted living facility with separate living quarters where participants and their caregivers reside is acceptable) Willing not to start a behavioral or other treatment program for sleep or wake difficulties and not to start a new treatment for other symptoms of AD-D during participation in the study Has a reliable and competent caregiver (or caregiver and informants) who can accompany the participant to study visits, administer study medication on a nightly basis and provide information on the status of the participant For participants taking a cholinesterase inhibitor and/or memantine, dosing regimen must have been stable for at least 3 months Inclusion Criteria (Extension Phase): Completed the Core Study (End of Study [EOS] Visit). Participants who participated in the Core Study and completed the EOS Visit within 30 days may return to participate in the Extension Phase as long as there are no contraindications due to ongoing adverse events or prohibited medications. Inclusion Criteria for Caregivers: Able to provide informed consent Spends at least 10 hours per week with the participant Able to meet caregiver requirements Willing to provide information on himself/herself regarding sleep quality and caregiver Burden Exclusion Criteria: A diagnosis of vascular dementia, dementia following multiple strokes, or any synucleinopathy / Lewy body disorder. This includes Dementia with Lewy Bodies and Parkinson's disease with or without dementia. A current diagnosis of moderate to severe obstructive sleep apnea (OSA) or central sleep apnea, or current use of continuous positive airways pressure even if mild severity of OSA, restless legs syndrome, periodic limb movement disorder (with awakenings), or narcolepsy An Apnea-Hypopnea Index or equivalent ≥15 events/hour on diagnostic sleep study conducted prior to Baseline or within 6 months of Screening A clinically significant movement disorder that would affect the differentiation of sleep and wake by the actigraphy analytic algorithm Current symptoms or history during the past year of Rapid Eye Movement Behavior Disorder or sleep-related violent behavior Probable Major Depression, as evidenced by score >10 on the Cornell Scale for Depression in Dementia at Screening Unable to tolerate wearing the actigraph. At a minimum, participants must be able to wear the actigraph for 5 complete days out of 7 days' data. A day will be considered complete as long as data from 90% of the 24-hour period are able to be scored. Excessive caffeine use that in the opinion of the investigator contributes to the participant's Irregular Sleep-Wake Rhythm Disorder (ISWRD) History of drug or alcohol dependency or abuse within approximately the previous 2 years Reports habitually consuming more than 14 drinks containing alcohol per week or habitually consumes alcohol within 3 hours before bedtime and unwilling to limit alcohol intake to 2 or fewer drinks per day or forego having alcohol within 3 hours before bedtime for the duration of his/her participation in the study Known to be human immunodeficiency virus positive Active viral hepatitis (B or C) as demonstrated by positive serology at Screening A prolonged QTcF interval (QTcF >450 milliseconds[ms]) as demonstrated by a repeated electrocardiogram (ECG) at Screening (repeated only if initial ECG indicates a QTcF interval >450 ms) (participants with evidence of bundle branch block are not excluded if the block is not clinically significant, as documented by the investigator in the source document) Current evidence of clinically significant disease that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments Any history of a medical or psychiatric condition other than Alzheimer's Disease dementia that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments History of malignancy within the previous 5 years except for adequately treated basal cell or squamous cell skin cancer or cervical carcinoma in situ Any suicidal ideation with intent with or without a plan, at the time of or within 6 months of Screening, as indicated by answering "Yes" to questions 4 and 5 on the Suicidal Ideation section of the electronic version of the Columbia Suicide Severity Rating Scale (eC-SSRS) Any suicidal behavior within the past 10 years based on the eC-SSRS History of violence toward the caregiver or others Scheduled for surgery using general anesthesia during the study Used any prohibited prescription or over-the-counter concomitant medications within 1 week or 5 half-lives, whichever is longer, before starting actigraphy during Screening Used any modality of treatment for ISWRD between Screening and Randomization based on approaches related to circadian rhythms, including phototherapy (light therapy), melatonin and melatonin agonists Failed treatment with Belsomra (efficacy and/or safety) following treatment with an appropriate dose and of adequate duration in the opinion of the investigator Transmeridian travel across more than 3 time zones between Screening and Randomization, or plans to travel across more than 3 time zones during the study Hypersensitivity to lemborexant or to its excipients Currently enrolled in another clinical trial, except for observational studies with no treatment component Used any investigational drug or device before informed consent (ie, within 30 days or 5× the investigational drug half-life whichever is longer or 6 months for potential disease-modifying drugs) Previously participated in any clinical trial of lemborexant

Facility Information:

Facility Name

Facility #1

City

Little Rock

State/Province

Arkansas

ZIP/Postal Code

72205

Country

United States

Facility Name

Facility #1

City

Rogers

State/Province

Arkansas

ZIP/Postal Code

72758

Country

United States

Facility Name

Facility #1

City

Costa Mesa

State/Province

California

ZIP/Postal Code

92626

Country

United States

Facility Name

Facility #1

City

Fullerton

State/Province

California

ZIP/Postal Code

92835

Country

United States

Facility Name

Facility #1

City

Glendale

State/Province

California

ZIP/Postal Code

91206

Country

United States

Facility Name

Facility #1

City

Irvine

State/Province

California

ZIP/Postal Code

92614

Country

United States

Facility Name

Facility #1

City

Irvine

State/Province

California

ZIP/Postal Code

92618

Country

United States

Facility Name

Facility #1

City

La Jolla

State/Province

California

ZIP/Postal Code

92037-0949

Country

United States

Facility Name

Facility #1

City

San Diego

State/Province

California

ZIP/Postal Code

92103

Country

United States

Facility Name

Facility #1

City

Santa Monica

State/Province

California

ZIP/Postal Code

90404

Country

United States

Facility Name

Facility #1

City

Bradenton

State/Province

Florida

ZIP/Postal Code

34205

Country

United States

Facility Name

Facility #1

City

Brandon

State/Province

Florida

ZIP/Postal Code

33511

Country

United States

Facility Name

Facility #1

City

Brooksville

State/Province

Florida

ZIP/Postal Code

34601

Country

United States

Facility Name

Facility #1

City

Hallandale Beach

State/Province

Florida

ZIP/Postal Code

33009

Country

United States

Facility Name

Facility #1

City

Miami Lakes

State/Province

Florida

ZIP/Postal Code

33014

Country

United States

Facility Name

Facility #1

City

Miami Springs

State/Province

Florida

ZIP/Postal Code

33016

Country

United States

Facility Name

Facility #1

City

Miami

State/Province

Florida

ZIP/Postal Code

33137

Country

United States

Facility Name

Facility #1

City

Miami

State/Province

Florida

ZIP/Postal Code

33165

Country

United States

Facility Name

Facility #1

City

Orlando

State/Province

Florida

ZIP/Postal Code

32806

Country

United States

Facility Name

Facility #2

City

Orlando

State/Province

Florida

ZIP/Postal Code

32806

Country

United States

Facility Name

Facility #1

City

Sunrise

State/Province

Florida

ZIP/Postal Code

33351

Country

United States

Facility Name

Facility #2

City

Tampa

State/Province

Florida

ZIP/Postal Code

33613

Country

United States

Facility Name

Facility #1

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30331

Country

United States

Facility Name

Facility #1

City

Columbus

State/Province

Georgia

ZIP/Postal Code

31909

Country

United States

Facility Name

Facility #1

City

Macon

State/Province

Georgia

ZIP/Postal Code

31201

Country

United States

Facility Name

Facility #1

City

Wichita

State/Province

Kansas

ZIP/Postal Code

67207

Country

United States

Facility Name

Facility #1

City

Belmont

State/Province

Massachusetts

ZIP/Postal Code

02478

Country

United States

Facility Name

Nevada Senior Services (NSS) Adult Day Care Center

City

Henderson

State/Province

Nevada

Country

United States

Facility Name

Facility #1

City

Las Vegas

State/Province

Nevada

ZIP/Postal Code

89104

Country

United States

Facility Name

Facility #1

City

Toms River

State/Province

New Jersey

ZIP/Postal Code

08755

Country

United States

Facility Name

Facility #2

City

Toms River

State/Province

New Jersey

ZIP/Postal Code

08755

Country

United States

Facility Name

Facility #1

City

Charlotte

State/Province

North Carolina

ZIP/Postal Code

28270

Country

United States

Facility Name

Facility #2

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27705

Country

United States

Facility Name

Facility #1

City

Raleigh

State/Province

North Carolina

ZIP/Postal Code

27612

Country

United States

Facility Name

Facility #1

City

Norristown

State/Province

Pennsylvania

ZIP/Postal Code

19401

Country

United States

Facility Name

Facility #1

City

Willow Grove

State/Province

Pennsylvania

ZIP/Postal Code

19090

Country

United States

Facility Name

Facility #1

City

Columbia

State/Province

South Carolina

ZIP/Postal Code

29203

Country

United States

Facility Name

Eisai Trial Site #1

City

Nagoya

State/Province

Aichi

ZIP/Postal Code

451-8511

Country

Japan

Facility Name

Eisai Trial Site #1

City

Fujisawa

State/Province

Kanagawa

ZIP/Postal Code

251-0038

Country

Japan

Facility Name

Eisai Trial Site #1

City

Kawasaki-shi

State/Province

Kanagawa

ZIP/Postal Code

210-0852

Country

Japan

Facility Name

Eisai Trial Site #1

City

Wako

State/Province

Saitama

ZIP/Postal Code

351-0111

Country

Japan

Facility Name

Eisai Trial Site #1

City

Kodaira

State/Province

Tokyo

ZIP/Postal Code

187-8551

Country

Japan

Facility Name

Eisai Trial Site #1

City

Setagaya

State/Province

Tokyo

ZIP/Postal Code

156-0041

Country

Japan

Facility Name

Eisai Trial Site #1

City

Shinjuku

State/Province

Tokyo

ZIP/Postal Code

169-0073

Country

Japan

Facility Name

Eisai Trial Site #1

City

Tachikawa-shi

State/Province

Tokyo

ZIP/Postal Code

190-8531

Country

Japan

Facility Name

Brighton and Sussex Medical School

City

Brighton

State/Province

East Sussex

ZIP/Postal Code

BN1 9PX

Country

United Kingdom

Facility Name

Cognitive Treatment and Research Unit

City

Crowborough

State/Province

East Sussex

ZIP/Postal Code

TN6 1NY

Country

United Kingdom

Facility Name

University of Edinburgh - PPDS

City

Edinburgh

ZIP/Postal Code

EH1 64UX

Country

United Kingdom

12. IPD Sharing Statement

Learn more about this trial

Study of Lemborexant for Irregular Sleep-Wake Rhythm Disorder and Mild to Moderate Alzheimer's Disease Dementia

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Study of Lemborexant for Irregular Sleep-Wake Rhythm Disorder and Mild to Moderate Alzheimer's Disease Dementia

Irregular Sleep-Wake Rhythm Disorder

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial