CompletedPhase 2Results posted

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

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

Lead sponsor

Eisai Inc.

Asset

Lemborexant

Listed sites

Recruiting sites

Enrollment

actual

Study population

Alzheimer’s disease

Key I/E criteria

•Alzheimer's disease•MMSE 10-26•Study partner/caregiver required

Primary endpoint

•Core Phase

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Eudract number2017-003306-40

Org study IDE2006-G000-202

NCT IDNCT03001557

Timeline

Milestones

Study start2016-12-20actual

Study first posted2016-12-23estimated

Primary completion2018-07-26actual

Results first posted2020-01-14actual

Study completion2020-04-17actual

Last update posted2021-05-17actual

Assets

Drug assets

Lemborexant

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age60 Years

Maximum age90 Years

SexAll

Healthy volunteersNot accepted

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

Endpoints (106)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Behavior / neuropsychiatric

Fluid / digital biomarkers

Executive function / language

Safety / tolerability / PK

Executive function / language

2 endpoints

Other/protocol endpoint

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

Time frame:Day 29

change from baseline, improvement

Other_pre_specified/registry result

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

Time frame:Day 29

change from baseline, improvement

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Core Phase: Lemborexant-matched PlaceboGlobal score: Marked improvementn=12 Participants	1	-
Global score: Moderate improvementn=12 Participants	1	-
Global score: Minimal improvementn=12 Participants	4	-
Global score: No changen=12 Participants	6	-
Global score: Minimal worseningn=12 Participants	0	-
Global score : Moderate worseningn=12 Participants	0	-
Global score : Marked worseningn=12 Participants	0	-
Core Phase: Lemborexant 2.5 mgGlobal score: Marked improvementn=12 Participants	0	-
Global score: Moderate improvementn=12 Participants	0	-
Global score: Minimal improvementn=12 Participants	4	-
Global score: No changen=12 Participants	5	-
Global score: Minimal worseningn=12 Participants	3	-
Global score : Moderate worseningn=12 Participants	0	-
Global score : Marked worseningn=12 Participants	0	-
Core Phase: Lemborexant 5 mgGlobal score: Marked improvementn=13 Participants	0	-
Global score: Moderate improvementn=13 Participants	2	-
Global score: Minimal improvementn=13 Participants	4	-
Global score: No changen=13 Participants	4	-
Global score: Minimal worseningn=13 Participants	2	-
Global score : Moderate worseningn=13 Participants	0	-
Global score : Marked worseningn=13 Participants	0	-
Core Phase: Lemborexant 10 mgGlobal score: Marked improvementn=13 Participants	0	-
Global score: Moderate improvementn=13 Participants	1	-
Global score: Minimal improvementn=13 Participants	5	-
Global score: No changen=13 Participants	3	-
Global score: Minimal worseningn=13 Participants	3	-
Global score : Moderate worseningn=13 Participants	0	-
Global score : Marked worseningn=13 Participants	0	-
Core Phase: Lemborexant 15 mgGlobal score: Marked improvementn=12 Participants	0	-
Global score: Moderate improvementn=12 Participants	0	-
Global score: Minimal improvementn=12 Participants	3	-
Global score: No changen=12 Participants	7	-
Global score: Minimal worseningn=12 Participants	1	-
Global score : Moderate worseningn=12 Participants	0	-
Global score : Marked worseningn=12 Participants	0	-

Behavior / neuropsychiatric

72 endpoints

Primary/protocol endpoint

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

Time frame:Baseline, Week 1

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 2

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 3

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 4

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 1

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 2

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 3

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 4

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 1

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 2

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 3

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 4

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 1

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 2

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 3

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 4

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 1

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 2

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 3

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 4

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 1

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 2

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 3

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 4

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 1

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 1

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 2

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 3

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 4

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 1

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 2

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 3

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 4

change from baseline, improvement

Primary/registry result

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

Time frame:Baseline, Week 1

change from baseline, improvement

Posted result

Group	Value (mean), percentage of sleep time	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	76.34	6.559
Change at Week 1n=12 Participants	0.14	5.766
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	77.64	7.883
Change at Week 1n=11 Participants	2.43	3.910
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	78.45	6.844
Change at Week 1n=13 Participants	3.87	4.646
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	76.38	8.037
Change at Week 1n=13 Participants	-0.17	5.861
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	77.35	8.624
Change at Week 1n=12 Participants	0.05	4.475

Primary/registry result

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

Time frame:Baseline, Week 2

change from baseline, improvement

Posted result

Group	Value (mean), percentage of sleep time	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	76.34	6.559
Change at Week 2n=12 Participants	-1.31	7.004
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	77.64	7.883
Change at Week 2n=10 Participants	2.17	2.833
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	78.45	6.844
Change at Week 2n=13 Participants	1.65	4.644
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	76.38	8.037
Change at Week 2n=13 Participants	-1.41	5.896
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	77.35	8.624
Change at Week 2n=12 Participants	-0.07	5.449

Primary/registry result

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

Time frame:Baseline, Week 3

change from baseline, improvement

Posted result

Group	Value (mean), percentage of sleep time	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	76.34	6.559
Change at Week 3n=11 Participants	-0.30	10.552
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	77.64	7.883
Change at Week 3n=11 Participants	1.68	3.229
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	78.45	6.844
Change at Week 3n=12 Participants	0.91	7.571
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	76.38	8.037
Change at Week 3n=12 Participants	-1.49	4.442
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	77.35	8.624
Change at Week 3n=12 Participants	1.10	7.112

Primary/registry result

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

Time frame:Baseline, Week 4

change from baseline, improvement

Posted result

Group	Value (mean), percentage of sleep time	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	76.34	6.559
Change at Week 4n=11 Participants	-0.78	9.555
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	77.64	7.883
Change at Week 4n=11 Participants	1.68	4.696
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	78.45	6.844
Change at Week 4n=12 Participants	0.00	5.547
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	76.38	8.037
Change at Week 4n=11 Participants	-1.04	5.920
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	77.35	8.624
Change at Week 4n=12 Participants	-0.81	7.735

Least square mean (LSM) difference3.17795% CI-0.741 - 7.096p0.1099MMRM

LSM Difference2.80295% CI-1.119 - 6.723p0.1576MMRM

LSM Difference-0.96095% CI-4.777 - 2.857p0.6160MMRM

LSM Difference0.71395% CI-3.160 - 4.585p0.7135MMRM

Primary/registry result

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

Time frame:Baseline, Week 1

change from baseline, improvement

Posted result

Group	Value (mean), percentage of immobile bouts	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	58.51	12.923
Change at Week 1n=12 Participants	-1.43	9.294
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	53.87	17.594
Change at Week 1n=11 Participants	-5.80	11.388
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	50.07	12.493
Change at Week 1n=13 Participants	-8.16	8.802
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	54.75	16.380
Change at Week 1n=12 Participants	-2.55	11.756
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	54.78	15.338
Change at Week 1n=12 Participants	-3.52	8.882

Primary/registry result

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

Time frame:Baseline, Week 2

change from baseline, improvement

Posted result

Group	Value (mean), percentage of immobile bouts	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	58.51	12.923
Change at Week 2n=12 Participants	2.52	11.845
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	53.87	17.594
Change at Week 2n=10 Participants	-6.91	5.994
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	50.07	12.493
Change at Week 2n=13 Participants	-4.95	8.399
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	54.75	16.380
Change at Week 2n=13 Participants	0.34	14.194
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	54.78	15.338
Change at Week 2n=12 Participants	-3.18	8.971

Primary/registry result

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

Time frame:Baseline, Week 3

change from baseline, improvement

Posted result

Group	Value (mean), percentage of immobile bouts	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	58.51	12.923
Change at Week 3n=11 Participants	-3.30	18.512
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	53.87	17.594
Change at Week 3n=11 Participants	-2.79	7.541
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	50.07	12.493
Change at Week 3n=12 Participants	-5.22	11.974
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	54.75	16.380
Change at Week 3n=12 Participants	0.36	9.018
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	54.78	15.338
Change at Week 3n=12 Participants	-4.92	9.572

Primary/registry result

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

Time frame:Baseline, Week 4

change from baseline, improvement

Posted result

Group	Value (mean), percentage of immobile bouts	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	58.51	12.923
Change at Week 4n=11 Participants	-1.39	19.383
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	53.87	17.594
Change at Week 4n=11 Participants	-1.35	8.821
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	50.07	12.493
Change at Week 4n=12 Participants	-1.96	8.459
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	54.75	16.380
Change at Week 4n=11 Participants	-0.45	13.389
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	54.78	15.338
Change at Week 4n=12 Participants	-1.68	12.683

LSM Difference-5.09895% CI-12.240 - 2.045p0.1582MMRM

LSM Difference-6.10595% CI-13.332 - 1.122p0.0961MMRM

LSM Difference0.68095% CI-6.262 - 7.623p0.8449MMRM

LSM Difference-3.14095% CI-10.178 - 3.897p0.3747MMRM

Primary/registry result

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

Time frame:Baseline, Week 1

change from baseline, improvement

Posted result

Group	Value (mean), minutes	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	20.32	6.625
Change at Week 1n=12 Participants	-1.65	5.078
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	20.40	5.140
Change at Week 1n=11 Participants	-1.99	2.825
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	20.62	5.898
Change at Week 1n=13 Participants	-0.51	6.522
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	21.89	4.885
Change at Week 1n=12 Participants	-0.82	5.722
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	21.94	7.790
Change at Week 1n=12 Participants	1.54	5.378

Primary/registry result

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

Time frame:Baseline, Week 2

change from baseline, improvement

Posted result

Group	Value (mean), minutes	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	20.32	6.625
Change at Week 2n=12 Participants	-0.32	7.904
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	20.40	5.140
Change at Week 2n=10 Participants	1.79	12.957
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	20.62	5.898
Change at Week 2n=13 Participants	4.71	13.845
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	21.89	4.885
Change at Week 2n=12 Participants	1.54	6.333
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	21.94	7.790
Change at Week 2n=12 Participants	2.57	6.708

Primary/registry result

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

Time frame:Baseline, Week 3

change from baseline, improvement

Posted result

Group	Value (mean), minutes	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	20.32	6.625
Change at Week 3n=11 Participants	-2.88	7.928
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	20.40	5.140
Change at Week 3n=11 Participants	3.67	7.833
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	20.62	5.898
Change at Week 3n=11 Participants	-0.52	4.595
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	21.89	4.885
Change at Week 3n=12 Participants	-0.64	5.482
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	21.94	7.790
Change at Week 3n=12 Participants	2.76	7.489

Primary/registry result

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

Time frame:Baseline, Week 4

change from baseline, improvement

Posted result

Group	Value (mean), minutes	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	20.32	6.625
Change at Week 4n=11 Participants	-1.26	8.621
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	20.40	5.140
Change at Week 4n=11 Participants	-0.43	8.053
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	20.62	5.898
Change at Week 4n=11 Participants	3.16	8.140
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	21.89	4.885
Change at Week 4n=11 Participants	-2.03	4.947
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	21.94	7.790
Change at Week 4n=12 Participants	3.38	12.354

LSM Difference1.93295% CI-2.601 - 6.465p0.3966MMRM

LSM Difference3.38695% CI-1.125 - 7.897p0.1381MMRM

LSM Difference1.33795% CI-3.104 - 5.778p0.5487MMRM

LSM Difference4.32095% CI-0.153 - 8.793p0.0581MMRM

Primary/registry result

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

Time frame:Baseline, Week 1

change from baseline, improvement

Posted result

Group	Value (mean), percentage of wake time	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	69.74	12.609
Change at Week 1n=12 Participants	0.59	4.177
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	70.57	11.669
Change at Week 1n=11 Participants	-2.41	6.726
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	72.53	11.473
Change at Week 1n=13 Participants	1.09	6.793
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	67.19	11.523
Change at Week 1n=12 Participants	-1.55	9.216
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	70.67	11.221
Change at Week 1n=12 Participants	-2.37	8.779

Primary/registry result

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

Time frame:Baseline, Week 2

change from baseline, improvement

Posted result

Group	Value (mean), percentage of wake time	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	69.74	12.609
Change at Week 2n=12 Participants	2.14	2.773
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	70.57	11.669
Change at Week 2n=10 Participants	-1.54	6.550
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	72.53	11.473
Change at Week 2n=13 Participants	1.04	7.511
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	67.19	11.523
Change at Week 2n=12 Participants	-3.16	12.816
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	70.67	11.221
Change at Week 2n=12 Participants	-0.63	5.617

Primary/registry result

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

Time frame:Baseline, Week 3

change from baseline, improvement

Posted result

Group	Value (mean), percentage of wake time	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	69.74	12.609
Change at Week 3n=11 Participants	1.64	5.451
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	70.57	11.669
Change at Week 3n=11 Participants	-2.37	6.239
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	72.53	11.473
Change at Week 3n=12 Participants	2.34	8.370
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	67.19	11.523
Change at Week 3n=12 Participants	-4.99	11.479
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	70.67	11.221
Change at Week 3n=12 Participants	-1.83	5.579

Primary/registry result

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

Time frame:Baseline, Week 4

change from baseline, improvement

Posted result

Group	Value (mean), percentage of wake time	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	69.74	12.609
Change at Week 4n=11 Participants	2.03	6.841
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	70.57	11.669
Change at Week 4n=11 Participants	-2.29	7.724
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	72.53	11.473
Change at Week 4n=12 Participants	3.62	8.586
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	67.19	11.523
Change at Week 4n=11 Participants	-2.65	9.627
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	70.67	11.221
Change at Week 4n=12 Participants	-0.43	5.848

LSM Difference-3.43795% CI-8.481 - 1.608p0.1777MMRM

LSM Difference1.45895% CI-3.564 - 6.479p0.5630MMRM

LSM Difference-4.99495% CI-9.946 - -0.041p0.0482MMRM

LSM Difference-2.59395% CI-7.599 - 2.413p0.3036MMRM

Primary/registry result

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

Time frame:Baseline, Week 1

change from baseline, improvement

Posted result

Group	Value (mean), percentage of immobile bouts	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	92.43	18.547
Change at Week 1n=12 Participants	-0.14	6.968
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	85.72	16.137
Change at Week 1n=11 Participants	4.22	9.988
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	86.53	18.705
Change at Week 1n=13 Participants	-2.18	10.571
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	94.76	17.262
Change at Week 1n=12 Participants	2.01	13.017
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	87.96	15.928
Change at Week 1n=12 Participants	3.25	13.006

Primary/registry result

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

Time frame:Baseline, Week 2

change from baseline, improvement

Posted result

Group	Value (mean), percentage of immobile bouts	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	92.43	18.547
Change at Week 2n=12 Participants	-3.76	3.940
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	85.72	16.137
Change at Week 2n=12 Participants	4.12	8.671
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	86.53	18.705
Change at Week 2n=13 Participants	-2.36	11.453
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	94.76	17.262
Change at Week 2n=13 Participants	5.09	19.006
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	87.96	15.928
Change at Week 2n=12 Participants	1.78	9.271

Primary/registry result

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

Time frame:Baseline, Week 3

change from baseline, improvement

Posted result

Group	Value (mean), percentage of immobile bouts	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	92.43	18.547
Change at Week 3n=11 Participants	-1.65	7.980
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	85.72	16.137
Change at Week 3n=11 Participants	4.70	9.674
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	86.53	18.705
Change at Week 3n=12 Participants	-3.69	13.236
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	94.76	17.262
Change at Week 3n=12 Participants	6.88	16.704
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	87.96	15.928
Change at Week 3n=12 Participants	2.10	8.631

Primary/registry result

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

Time frame:Baseline, Week 4

change from baseline, improvement

Posted result

Group	Value (mean), percentage of immobile bouts	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	92.43	18.547
Change at Week 4n=11 Participants	-3.01	10.620
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	85.72	16.137
Change at Week 4n=11 Participants	4.55	10.930
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	86.53	18.705
Change at Week 4n=12 Participants	-6.93	14.428
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	94.76	17.262
Change at Week 4n=11 Participants	2.77	13.407
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	87.96	15.928
Change at Week 4n=12 Participants	1.22	8.054

LSM Difference4.84595% CI-2.624 - 12.313p0.1991MMRM

LSM Difference-3.87295% CI-11.263 - 3.518p0.2982MMRM

LSM Difference6.77695% CI-0.474 - 14.025p0.0664MMRM

LSM Difference3.01795% CI-4.344 - 10.379p0.4148MMRM

Primary/registry result

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

Time frame:Baseline, Week 1

change from baseline, improvement

Posted result

Group	Value (mean), minutes	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	18.36	4.620
Change at Week 1n=12 Participants	2.15	2.539
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	20.65	3.638
Change at Week 1n=11 Participants	0.09	4.056
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	23.13	5.919
Change at Week 1n=13 Participants	-1.12	5.202
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	19.84	3.364
Change at Week 1n=12 Participants	-0.40	3.394
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	23.30	10.862
Change at Week 1n=12 Participants	-3.19	10.405

Primary/registry result

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

Time frame:Baseline, Week 2

change from baseline, improvement

Posted result

Group	Value (mean), minutes	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	18.36	4.620
Change at Week 2n=12 Participants	0.25	2.999
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	20.65	3.638
Change at Week 2n=10 Participants	-0.88	4.679
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	23.13	5.919
Change at Week 2n=13 Participants	-2.52	5.965
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	19.84	3.364
Change at Week 2n=12 Participants	-0.80	2.961
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	23.30	10.862
Change at Week 2n=12 Participants	-3.95	8.980

Primary/registry result

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

Time frame:Baseline, Week 3

change from baseline, improvement

Posted result

Group	Value (mean), minutes	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	18.36	4.620
Change at Week 3n=11 Participants	-0.14	3.249
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	20.65	3.638
Change at Week 3n=11 Participants	-1.17	4.056
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	23.13	5.919
Change at Week 3n=12 Participants	-3.80	3.701
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	19.84	3.364
Change at Week 3n=12 Participants	-0.68	2.292
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	23.30	10.862
Change at Week 3n=12 Participants	-4.15	10.264

Primary/registry result

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

Time frame:Baseline, Week 4

change from baseline, improvement

Posted result

Group	Value (mean), minutes	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	18.36	4.620
Change at Week 4n=11 Participants	1.00	4.568
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	20.65	3.638
Change at Week 4n=11 Participants	-1.31	3.639
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	23.13	5.919
Change at Week 4n=12 Participants	-2.80	5.727
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	19.84	3.364
Change at Week 4n=11 Participants	-0.03	2.307
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	23.30	10.862
Change at Week 4n=12 Participants	-5.30	9.745

LSM Difference0.06395% CI-2.452 - 2.579p0.9599MMRM

LSM Difference-0.23895% CI-2.817 - 2.342p0.8541MMRM

LSM Difference-0.29395% CI-2.745 - 2.160p0.8117MMRM

LSM Difference-1.55795% CI-4.113 - 1.000p0.2274MMRM

Primary/registry result

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

Time frame:Baseline, Week 1

change from baseline, improvement

Posted result

Group	Value (mean), ratio	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	1.10	0.262
Change at Week 1n=12 Participants	-0.01	0.200
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	0.90	0.272
Change at Week 1n=11 Participants	0.06	0.218
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	0.98	0.295
Change at Week 1n=13 Participants	-0.03	0.237
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	1.10	0.295
Change at Week 1n=11 Participants	0.10	0.271
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	1.03	0.330
Change at Week 1n=12 Participants	-0.01	0.278

Primary/registry result

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

Time frame:Baseline, Week 1

change from baseline, improvement

Posted result

Group	Value (mean), ratio	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	0.45	0.173
Change at Week 1n=12 Participants	0.04	0.083
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	0.47	0.111
Change at Week 1n=11 Participants	-0.02	0.089
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	0.49	0.118
Change at Week 1n=13 Participants	0.04	0.115
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	0.46	0.160
Change at Week 1n=11 Participants	-0.00	0.155
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	0.41	0.104
Change at Week 1n=12 Participants	0.06	0.063

Primary/registry result

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

Time frame:Baseline, Week 2

change from baseline, improvement

Posted result

Group	Value (mean), ratio	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	0.45	0.173
Change at Week 2n=12 Participants	0.06	0.093
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	0.47	0.111
Change at Week 2n=9 Participants	-0.01	0.101
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	0.49	0.118
Change at Week 2n=12 Participants	0.03	0.133
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	0.46	0.160
Change at Week 2n=12 Participants	-0.06	0.091
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	0.41	0.104
Change at Week 2n=11 Participants	0.09	0.085

Primary/registry result

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

Time frame:Baseline, Week 3

change from baseline, improvement

Posted result

Group	Value (mean), ratio	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	0.45	0.173
Change at Week 3n=11 Participants	0.03	0.104
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	0.47	0.111
Change at Week 3n=11 Participants	-0.01	0.107
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	0.49	0.118
Change at Week 3n=12 Participants	0.03	0.115
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	0.46	0.160
Change at Week 3n=12 Participants	-0.04	0.136
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	0.41	0.104
Change at Week 3n=12 Participants	0.04	0.075

Primary/registry result

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

Time frame:Baseline, Week 4

change from baseline, improvement

Posted result

Group	Value (mean), ratio	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	0.45	0.173
Change at Week 4n=7 Participants	0.02	0.098
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	0.47	0.111
Change at Week 4n=10 Participants	0.01	0.119
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	0.49	0.118
Change at Week 4n=8 Participants	0.08	0.092
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	0.46	0.160
Change at Week 4n=8 Participants	0.03	0.127
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	0.41	0.104
Change at Week 4n=9 Participants	0.00	0.102

LSM Difference-0.03295% CI-0.094 - 0.029p0.2991MMRM

LSM Difference0.03395% CI-0.028 - 0.095p0.2861MMRM

LSM Difference-0.05295% CI-0.113 - 0.009p0.0938MMRM

LSM Difference0.00595% CI-0.055 - 0.066p0.8618MMRM

Primary/registry result

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

Time frame:Baseline, Week 1

change from baseline, improvement

Posted result

Group	Value (mean), activity count	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	1163.5	373.3
Change at Week 1n=12 Participants	200.9	633.3
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	1266.4	678.1
Change at Week 1n=11 Participants	-259.8	450.3
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	1163.2	591.8
Change at Week 1n=13 Participants	-243.2	333.6
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	1257.1	836.6
Change at Week 1n=11 Participants	-211.6	378.3
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	1490.4	963.1
Change at Week 1n=12 Participants	-434.2	509.1

Primary/registry result

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

Time frame:Baseline, Week 2

change from baseline, improvement

Posted result

Group	Value (mean), activity count	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	1163.5	373.3
Change at Week 2n=12 Participants	85.8	525.3
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	1266.4	678.1
Change at Week 2n=9 Participants	-259.8	244.9
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	1163.2	591.8
Change at Week 2n=12 Participants	-218.7	321.6
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	1257.1	836.6
Change at Week 2n=12 Participants	218.5	455.9
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	1490.4	963.1
Change at Week 2n=11 Participants	-246.1	637.6

Primary/registry result

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

Time frame:Baseline, Week 3

change from baseline, improvement

Posted result

Group	Value (mean), activity count	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	1163.5	373.3
Change at Week 3n=11 Participants	299.2	1070.2
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	1266.4	678.1
Change at Week 3n=11 Participants	-265.3	507.0
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	1163.2	591.8
Change at Week 3n=12 Participants	-233.0	369.3
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	1257.1	836.6
Change at Week 3n=12 Participants	-114.6	376.6
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	1490.4	963.1
Change at Week 3n=12 Participants	-396.1	543.9

Primary/registry result

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

Time frame:Baseline, Week 4

change from baseline, improvement

Posted result

Group	Value (mean), activity count	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	1163.5	373.3
Change at Week 4n=7 Participants	293.1	662.6
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	1266.4	678.1
Change at Week 4n=10 Participants	-334.0	476.4
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	1163.2	591.8
Change at Week 4n=8 Participants	-344.5	419.1
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	1257.1	836.6
Change at Week 4n=8 Participants	30.5	772.5
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	1490.4	963.1
Change at Week 4n=9 Participants	-160.7	471.3

LSM Difference-389.87395% CI-739.177 - -40.569p0.0294MMRM

LSM Difference-402.99495% CI-751.670 - -54.319p0.0243MMRM

LSM Difference-141.02695% CI-489.805 - 207.752p0.4209MMRM

LSM Difference-367.84595% CI-717.870 - -17.820p0.0398MMRM

Other/protocol endpoint

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

Time frame:Baseline, Day 29

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Other/protocol endpoint

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

Time frame:Baseline, Day 29

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Other/protocol endpoint

Extension Phase: Change From Baseline in SDI Total Score.

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

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Other_pre_specified/registry result

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

Time frame:Baseline, Day 29

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	3.8	4.13
Change at Day 29n=12 Participants	-2.8	3.64
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	13.1	17.77
Change at Day 29n=12 Participants	-3.4	9.23
Core Phase: Lemborexant 5 mgBaselinen=12 Participants	7.7	12.32
Change at Day 29n=12 Participants	-0.3	5.85
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	6.4	10.27
Change at Day 29n=13 Participants	-3.4	8.95
Core Phase: Lemborexant 15 mgBaselinen=11 Participants	5.5	5.73
Change at Day 29n=10 Participants	3.8	13.02

Other_pre_specified/registry result

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

Time frame:Baseline, Day 29

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	0.79	0.692
Change at Day 29n=12 Participants	-0.48	1.078
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	1.24	1.576
Change at Day 29n=12 Participants	-0.10	0.616
Core Phase: Lemborexant 5 mgBaselinen=12 Participants	0.74	0.653
Change at Day 29n=12 Participants	-0.33	0.503
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	0.66	0.748
Change at Day 29n=13 Participants	-0.09	0.574
Core Phase: Lemborexant 15 mgBaselinen=11 Participants	1.44	1.708
Change at Day 29n=11 Participants	-0.49	1.220

Other_pre_specified/registry result

Extension Phase: Change From Baseline in SDI Total Score.

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

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
Extension Phase: Lemborexant 5 mgBaselinen=5 Participants	1.36	1.948
Change at Day 133 (Visit 9)n=1 Participants	1.40	-
Change at Day 343 (Visit 16)n=1 Participants	0.60	-
Extension Phase: Lemborexant 10 mgBaselinen=12 Participants	0.74	0.728
Change at Day 133 (Visit 9)n=8 Participants	-0.45	0.600
Change at Day 223 (Visit 12)n=6 Participants	-0.60	0.693
Change at Day 313 (Visit 15)n=4 Participants	-0.65	0.574
Change at Day 343 (Visit 16)n=2 Participants	0.55	1.061
Change at Day 373 (Visit 17)n=1 Participants	-0.20	-
Change at Day 403 (Visit 18)n=5 Participants	-0.50	0.539
Change at Day 493 (Visit 19)n=3 Participants	-0.13	0.115
Change at Day 583 (Visit 20)n=2 Participants	-0.15	0.071
Change at Day 673 (Visit 21)n=1 Participants	-0.30	-
Change at Day 763 (Visit 22)n=2 Participants	-0.05	0.354
Extension Phase: Lemborexant 15 mgBaselinen=6 Participants	1.45	2.331
Change at Day 133 (Visit 9)n=3 Participants	-0.63	0.473
Change at Day 223 (Visit 12)n=3 Participants	0.17	0.306
Change at Day 313 (Visit 15)n=3 Participants	-0.17	1.266
Change at Day 343 (Visit 16)n=2 Participants	0.45	0.919
Change at Day 403 (Visit 18)n=4 Participants	-0.55	0.656
Change at Day 493 (Visit 19)n=1 Participants	-0.10	-
Change at Day 583 (Visit 20)n=2 Participants	-0.35	0.354
Change at Day 673 (Visit 21)n=2 Participants	-0.15	0.071

Fluid / digital biomarkers

30 endpoints

Primary/protocol endpoint

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

Time frame:Baseline, Week 2

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 3

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 4

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 1

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 2

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 3

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 4

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 1

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 2

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 3

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 4

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 1

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 2

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 3

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Week 4

change from baseline, improvement

Primary/registry result

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

Time frame:Baseline, Week 2

change from baseline, improvement

Posted result

Group	Value (mean), ratio	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	1.10	0.262
Change at Week 2n=12 Participants	-0.05	0.132
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	0.90	0.272
Change at Week 2n=9 Participants	0.14	0.325
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	0.98	0.295
Change at Week 2n=12 Participants	0.02	0.235
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	1.10	0.295
Change at Week 2n=12 Participants	0.07	0.143
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	1.03	0.330
Change at Week 2n=11 Participants	0.05	0.234

Primary/registry result

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

Time frame:Baseline, Week 3

change from baseline, improvement

Posted result

Group	Value (mean), ratio	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	1.10	0.262
Change at Week 3n=11 Participants	-0.06	0.243
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	0.90	0.272
Change at Week 3n=11 Participants	0.07	0.246
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	0.98	0.295
Change at Week 3n=12 Participants	-0.00	0.241
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	1.10	0.295
Change at Week 3n=12 Participants	-0.06	0.311
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	1.03	0.330
Change at Week 3n=12 Participants	-0.01	0.219

Primary/registry result

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

Time frame:Baseline, Week 4

change from baseline, improvement

Posted result

Group	Value (mean), ratio	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	1.10	0.262
Change at Week 4n=7 Participants	-0.10	0.324
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	0.90	0.272
Change at Week 4n=10 Participants	0.10	0.196
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	0.98	0.295
Change at Week 4n=8 Participants	0.02	0.157
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	1.10	0.295
Change at Week 4n=8 Participants	-0.12	0.274
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	1.03	0.330
Change at Week 4n=9 Participants	-0.10	0.222

LSM Difference0.08695% CI-0.060 - 0.232p0.2421MMRM

LSM Difference-0.01295% CI-0.155 - 0.131p0.8661MMRM

LSM Difference0.05795% CI-0.085 - 0.199p0.4251MMRM

LSM Difference0.02595% CI-0.116 - 0.166p0.7248MMRM

Primary/registry result

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

Time frame:Baseline, Week 1

change from baseline, improvement

Posted result

Group	Value (mean), activity count	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	8560.4	2631.2
Change at Week 1n=12 Participants	59.7	1832.6
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	11567.0	4266.3
Change at Week 1n=12 Participants	-731.4	3373.5
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	12158.1	3639.9
Change at Week 1n=13 Participants	42.5	1789.3
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	10662.1	5023.6
Change at Week 1n=11 Participants	-334.6	2659.2
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	11460.5	4954.3
Change at Week 1n=12 Participants	-111.2	2558.0

Primary/registry result

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

Time frame:Baseline, Week 2

change from baseline, improvement

Posted result

Group	Value (mean), activity count	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	8560.4	2631.2
Change at Week 2n=12 Participants	232.7	1829.1
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	11567.0	4266.3
Change at Week 2n=9 Participants	-968.8	2885.6
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	12158.1	3639.9
Change at Week 2n=12 Participants	-121.1	2137.3
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	10662.1	5023.6
Change at Week 2n=12 Participants	-564.2	1975.7
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	11460.5	4954.3
Change at Week 2n=11 Participants	-325.4	1585.4

Primary/registry result

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

Time frame:Baseline, Week 3

change from baseline, improvement

Posted result

Group	Value (mean), activity count	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	8560.4	2631.2
Change at Week 3n=11 Participants	300.3	2094.9
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	11567.0	4266.3
Change at Week 3n=11 Participants	-986.2	3502.0
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	12158.1	3639.9
Change at Week 3n=12 Participants	572.6	2216.0
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	10662.1	5023.6
Change at Week 3n=12 Participants	-828.3	1970.2
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	11460.5	4954.3
Change at Week 3n=12 Participants	-635.8	2413.6

Primary/registry result

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

Time frame:Baseline, Week 4

change from baseline, improvement

Posted result

Group	Value (mean), activity count	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	8560.4	2631.2
Change at Week 4n=7 Participants	1650.4	1815.3
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	11567.0	4266.3
Change at Week 4n=10 Participants	-1392.1	2249.3
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	12158.1	3639.9
Change at Week 4n=8 Participants	-477.4	963.2
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	10662.1	5023.6
Change at Week 4n=8 Participants	279.8	2204.0
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	11460.5	4954.3
Change at Week 4n=9 Participants	-457.8	1788.7

LSM Difference-1276.18095% CI-2878.587 - 326.226p0.1162MMRM

LSM Difference227.46495% CI-1382.850 - 1837.777p0.7781MMRM

LSM Difference-620.58195% CI-2170.342 - 929.179p0.4255MMRM

LSM Difference-577.82095% CI-2160.337 - 1004.697p0.4672MMRM

Primary/registry result

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

Time frame:Baseline, Week 1

change from baseline, improvement

Posted result

Group	Value (mean), activity count	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	7396.9	2728.3
Change at Week 1n=12 Participants	-141.1	1583.8
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	10300.6	4235.8
Change at Week 1n=11 Participants	-471.6	3414.4
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	10994.8	3601.8
Change at Week 1n=13 Participants	285.8	1788.6
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	9405.0	5133.9
Change at Week 1n=11 Participants	-123.0	2784.1
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	9970.0	4905.8
Change at Week 1n=12 Participants	323.0	2436.0

Primary/registry result

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

Time frame:Baseline, Week 2

change from baseline, improvement

Posted result

Group	Value (mean), activity count	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	7396.9	2728.3
Change at Week 2n=12 Participants	146.8	1603.7
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	10300.6	4235.8
Change at Week 2n=9 Participants	-708.9	2934.6
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	10994.8	3601.8
Change at Week 2n=12 Participants	97.6	2105.2
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	9405.0	5133.9
Change at Week 2n=12 Participants	-782.7	2141.4
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	9970.0	4905.8
Change at Week 2n=11 Participants	-79.3	1672.5

Primary/registry result

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

Time frame:Baseline, Week 3

change from baseline, improvement

Posted result

Group	Value (mean), activity count	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	7396.9	2728.3
Change at Week 3n=11 Participants	1.1	1862.7
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	10300.6	4235.8
Change at Week 3n=11 Participants	-721.0	3502.2
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	10994.8	3601.8
Change at Week 3n=12 Participants	805.6	2195.6
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	9405.0	5133.9
Change at Week 3n=12 Participants	-713.7	2178.3
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	9970.0	4905.8
Change at Week 3n=12 Participants	-239.7	2592.5

Primary/registry result

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

Time frame:Baseline, Week 4

change from baseline, improvement

Posted result

Group	Value (mean), activity count	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	7396.9	2728.3
Change at Week 4n=7 Participants	1357.3	1801.9
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	10300.6	4235.8
Change at Week 4n=10 Participants	-1058.0	2170.9
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	10994.8	3601.8
Change at Week 4n=8 Participants	-132.9	840.7
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	9405.0	5133.9
Change at Week 4n=8 Participants	249.4	2694.7
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	9970.0	4905.8
Change at Week 4n=9 Participants	-297.1	1608.2

LSM Difference-839.08895% CI-2440.854 - 762.678p0.2984MMRM

LSM Difference651.92295% CI-962.835 - 2266.678p0.4218MMRM

LSM Difference-447.24595% CI-1998.440 - 1103.950p0.5655MMRM

LSM Difference-130.60395% CI-1706.478 - 1445.272p0.8686MMRM

Primary/registry result

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

Time frame:Baseline, Week 1

change from baseline, improvement

Posted result

Group	Value (mean), ratio	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	0.73	0.136
Change at Week 1n=12 Participants	-0.02	0.101
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	0.79	0.141
Change at Week 1n=11 Participants	0.01	0.080
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	0.82	0.089
Change at Week 1n=13 Participants	0.03	0.067
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	0.77	0.165
Change at Week 1n=11 Participants	0.02	0.096
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	0.76	0.148
Change at Week 1n=12 Participants	0.07	0.073

Primary/registry result

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

Time frame:Baseline, Week 2

change from baseline, improvement

Posted result

Group	Value (mean), ratio	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	0.73	0.136
Change at Week 2n=12 Participants	-0.00	0.073
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	0.79	0.141
Change at Week 2n=9 Participants	0.01	0.063
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	0.82	0.089
Change at Week 2n=12 Participants	0.03	0.052
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	0.77	0.165
Change at Week 2n=12 Participants	-0.05	0.112
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	0.76	0.148
Change at Week 2n=11 Participants	0.05	0.091

Primary/registry result

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

Time frame:Baseline, Week 3

change from baseline, improvement

Posted result

Group	Value (mean), ratio	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	0.73	0.136
Change at Week 3n=11 Participants	-0.01	0.143
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	0.79	0.141
Change at Week 3n=11 Participants	0.01	0.088
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	0.82	0.089
Change at Week 3n=12 Participants	0.04	0.063
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	0.77	0.165
Change at Week 3n=12 Participants	0.01	0.090
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	0.76	0.148
Change at Week 3n=12 Participants	0.06	0.080

Primary/registry result

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

Time frame:Baseline, Week 4

change from baseline, improvement

Posted result

Group	Value (mean), ratio	Standard deviation
Core Phase: Lemborexant-matched PlaceboBaselinen=12 Participants	0.73	0.136
Change at Week 4n=7 Participants	-0.00	0.117
Core Phase: Lemborexant 2.5 mgBaselinen=12 Participants	0.79	0.141
Change at Week 4n=10 Participants	0.01	0.060
Core Phase: Lemborexant 5 mgBaselinen=13 Participants	0.82	0.089
Change at Week 4n=8 Participants	0.05	0.049
Core Phase: Lemborexant 10 mgBaselinen=13 Participants	0.77	0.165
Change at Week 4n=8 Participants	0.01	0.136
Core Phase: Lemborexant 15 mgBaselinen=12 Participants	0.76	0.148
Change at Week 4n=9 Participants	0.02	0.069

LSM Difference0.02095% CI-0.034 - 0.074p0.4638MMRM

LSM Difference0.06095% CI0.005 - 0.115p0.0322MMRM

LSM Difference0.00395% CI-0.051 - 0.056p0.9144MMRM

LSM Difference0.05795% CI0.004 - 0.110p0.0364MMRM

Safety / tolerability / PK

2 endpoints

Other/protocol endpoint

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)

event count, event

Other_pre_specified/registry result

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)

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Core Phase: Lemborexant-matched PlaceboTEAEsn=12 Participants	4	-
SAEsn=12 Participants	0	-
Core Phase: Lemborexant 2.5 mgTEAEsn=12 Participants	3	-
SAEsn=12 Participants	0	-
Core Phase: Lemborexant 5 mgTEAEsn=13 Participants	3	-
SAEsn=13 Participants	0	-
Core Phase: Lemborexant 10 mgTEAEsn=13 Participants	4	-
SAEsn=13 Participants	0	-
Core Phase: Lemborexant 15 mgTEAEsn=12 Participants	6	-
SAEsn=12 Participants	0	-
Extension Phase: Lemborexant 5 mgTEAEsn=5 Participants	4	-
SAEsn=5 Participants	1	-
Extension Phase: Lemborexant 10 mgTEAEsn=14 Participants	10	-
SAEsn=14 Participants	2	-
Extension Phase: Lemborexant 15 mgTEAEsn=6 Participants	5	-
SAEsn=6 Participants	1	-

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.