Long-term Study of Lemborexant in Insomnia Disorder (SUNR... | NCT02952820

ID	Type	Description	Link
2015-001463-39	EudraCT Number

Label	Type	Description	Intervention Names
lemborexant 5 milligrams (mg)	Experimental	Lemborexant 5 mg will be taken orally in tablet form at home each night immediately before the time the participant intends to try to sleep.	Drug: lemborexant
lemborexant 10 mg	Experimental	Lemborexant 10 mg will be taken orally in tablet form at home each night immediately before the time the participant intends to try to sleep.	Drug: lemborexant
Placebo matched to lemborexant	Placebo Comparator	Lemborexant-matched placebo will be taken orally in tablet form at home each night immediately before the time the participant intends to try to sleep.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
lemborexant	Drug		lemborexant 10 mg lemborexant 5 milligrams (mg)
Placebo

Measure	Description	Time Frame
Change From Baseline in Subjective Sleep Onset Latency (sSOL) at Month 6	sSOL was defined as estimated minutes from the time that the participant attempted to sleep until sleep onset.	Baseline and Month 6

Measure	Description	Time Frame
Change From Baseline in sSOL at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1 and 3	sSOL was defined as estimated minutes from time attempted to sleep to sleep onset.	Baseline, (mean of 7 nights [approximately Week 1]), Months 1 and 3

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male or female, age 18 years or older at the time of informed consent
Meets the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM 5) criteria for Insomnia Disorder, as follows:
- Complains of dissatisfaction with nighttime sleep in the form of difficulty getting to sleep, difficulty staying asleep, and/or awakening earlier in the morning than desired despite adequate opportunity for sleep
- Frequency of complaint ≥3 times per week
- Duration of complaint ≥3 months
- Associated with complaint of daytime impairment
History of (Subjective Sleep Onset Latency) sSOL ≥30 minutes on at least 3 nights per week in the previous 4 weeks and/or subjective Wake after Sleep Onset (sWASO) ≥60 minutes on at least 3 nights per week in the previous 4 weeks
History of regular time spent in bed, either sleeping or trying to sleep, between 7 and 9 hours
Regular bedtime, between 21:00 and 01:00 and regular wake time, the time the participant gets out of bed for the day, between 05:00 and 10:00
Insomnia Severity Index (ISI) score ≥15
Confirmation of current insomnia symptoms as determined from the Sleep Diary completed on at least 7 consecutive mornings (minimum 5 of 7 for eligibility), such that sSOL ≥30 minutes on at least 3 of the 7 nights and/or sWASO ≥60 minutes on at least 3 of the 7 nights
Confirmation of time spent in bed, as determined from on the Sleep Diary completed on 7 mornings between the first and second screening visit, such that there are not more than 2 nights with duration of time spent in bed 7 hours and 10 hours
Confirmation of regular bedtimes and wake times such that the participant has a regular time spent in bed, either sleeping or trying to sleep, between 7 and 10 hours for the final 7 nights of the before visit 3.
Confirmation of regular bedtime between 21:00 and 01:00 and time of getting out of bed for the day between 05:00 and 10:00 for the final 7 nights of the before visit 3.
Willing and able to comply with all aspects of the protocol, including staying in bed for at least 7 hours each night
Willing to not start a behavioral or other treatment program for insomnia during the participants participation in the study

Exclusion Criteria:

A current diagnosis of sleep-related breathing disorder, periodic limb movement disorder, restless legs syndrome, circadian rhythm sleep disorder, or an exclusionary score on screening instruments to rule out individuals with symptoms of certain sleep disorders other than insomnia.
- STOPBang score greater than or equal to (>=) 5
- International Restless Legs Scale (IRLS) score >=16
- Epworth Sleepiness Scale (ESS) score >15
Reports symptoms potentially related to narcolepsy that in the clinical opinion of the investigator indicates the need for referral for a diagnostic evaluation for the presence of narcolepsy
Reports a history of sleep-related violent behavior, or sleep driving, or any other complex sleep-related behavior, eg, making phone calls, or preparing and eating food while asleep
For participants who underwent polysomnography (PSG) within the previous year:
- Age 18 to 64 years: Apnea Hypopnea Index ≥10, or Periodic Limb Movements with Arousal Index ≥10
- Age ≥65 years: Apnea Hypopnea Index >15, or Periodic Limb Movements with Arousal Index >15
Beck Depression Inventory - II (BDI II) score >19 at Screening
Beck Anxiety Inventory (BAI) score >15 at Screening
Habitually naps more than 3 times per week
Females who are breastfeeding or pregnant at Screening or Study Baseline
Females of childbearing potential who are not practicing acceptable pregnancy prevention methods (NOTE: All females will be considered to be of childbearing potential unless they are postmenopausal or have been sterilized surgically.)
Excessive caffeine use that in the opinion of the investigator contributes to the participant's insomnia, or habitually consumes caffeine-containing beverages after 18:00 and is unwilling to forego caffeine after 18:00 for the duration of his/her participation in the study
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 (females) or more than 21 drinks containing alcohol per week (males), or unwilling to limit alcohol intake to no more than 2 drinks per day or forego having alcohol within the 3 hours before bedtime for the duration of his/her participation in the study
A prolonged QT/QT interval corrected by Fridericia's formula (QTcF >450 ms) as demonstrated by a repeated electro cardiogram(ECG) at Screening (repeated only if initial ECG indicates a QTcF interval >450 ms)
Current evidence of clinically significant disease (e.g., cardiac, respiratory, gastrointestinal, renal, neurological [including participants who lack capacity and/or whose cognitive decline indicates disorientation to person/place/time and/or situation], or psychiatric disease or malignancy other than basal cell carcinoma) or chronic pain that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments
Comorbid nocturia resulting in frequent need to get out of bed to use the bathroom during the night
Scheduled for major surgery during the study
Used any prohibited prescription or over-the-counter concomitant medications within 1 week before the first dose of study medication
Used any modality of treatment for insomnia, including cognitive behavioral therapy or marijuana within 2 weeks before Screening
Failed treatment with suvorexant (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 in the 2 weeks before Screening, or between Screening and Study Baseline
Previously participated in any clinical trial of lemborexant

Name	Affiliation	Role
Eisai Medical Information	Eisai Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Facility # 1		Chandler	Arizona	85224	United States
Facility # 2

PubMed Identifier	Type	Citation	Retractions
41938624	Derived	Suzuki M, Yoshiike T, Khullar A, Kogo Y, Inabe K, Koebis M, Moline M, Cheng JY, Kumar D, Pinner K, Kuriyama K. Effects of lemborexant on sleep quality and its association with morning alertness: Post hoc analysis of two phase 3 trials. Sleep Med X. 2026 Mar 5;11:100183. doi: 10.1016/j.sleepx.2026.100183. eCollection 2026 Dec.
39823487

ID	Title	Description
FG000	Placebo	Participants received lemborexant-matched placebo, tablet, orally, once daily for up to Month 6 in the placebo-controlled treatment period. Then they were re-randomized to lemborexant 5 milligram (mg) or lemborexant 10 mg up to Month 12.
FG001	Lemborexant 5 mg

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Aug 13, 2018	Jan 24, 2020

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in Subjective Sleep Onset Latency (sSOL) at Month 6

sSOL was defined as estimated minutes from the time that the participant attempted to sleep until sleep onset.

The FAS was the group of randomized participants who received at least one dose of randomized study drug and had at least one postdose primary efficacy measurement. Number analyzed refers to participants evaluable for this outcome measure at specified time point.

Posted

Mean

Standard Deviation

minutes

Baseline and Month 6

ID	Title	Description
OG000	Placebo	Participants received lemborexant-matched placebo, tablet, orally, once daily for up to Month 6 in the placebo-controlled treatment period. Then they were re-randomized to lemborexant 5 mg or lemborexant 10 mg up to Month 12.
OG001	Lemborexant 5 mg	Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).
OG002	Lemborexant 10 mg	Participants received lemborexant 10 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).

Units	Counts
Participants	OG000318 OG001316 OG002315

Title

Denominators

Categories

Baseline

- ParticipantsOG000316
- ParticipantsOG001314
- ParticipantsOG002312

Title	Measurements

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Analysis was based on mixed effect model repeated measurement analysis (MMRM) model with log transformation of sSOL and factors for age group, region, treatment, visit (Month 6), and treatment-by-visit interaction as fixed effects, and the study baseline sSOL as a covariate. Missing values are imputed using multiple imputation and assumed to be missing not at random (missing not at random/complete case missing value [MNAR/CCMV]).	Mixed Models Analysis		<.0001		least squares geometric mean (LSGM)ratio	0.732			2-Sided	95	0.636	0.843					Superiority

Secondary

Change From Baseline in sSOL at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1 and 3

sSOL was defined as estimated minutes from time attempted to sleep to sleep onset.

Posted

Mean

Standard Deviation

minutes

Baseline, (mean of 7 nights [approximately Week 1]), Months 1 and 3

ID	Title	Description
OG000	Placebo	Participants received lemborexant-matched placebo, tablet, orally, once daily for up to Month 6 in the placebo-controlled treatment period. Then they were re-randomized to lemborexant 5 mg or lemborexant 10 mg up to Month 12.
OG001	Lemborexant 5 mg	Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).
OG002	Lemborexant 10 mg	Participants received lemborexant 10 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).

Secondary

Change From Baseline in Subjective Sleep Efficiency (sSE) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6

sSE was defined as percentage of subjective total sleep time (sTST) divided by subjective time spent in bed, calculated as the interval from the time the participant reported attempting to sleep until the time participant stopped trying to sleep for the night (operationalized as the time the participant got out of bed for the day), and time spent asleep derived from subjective time spent in bed minus sWASO.

Posted

Mean

Standard Deviation

percentage of sTST

Baseline, (mean of 7 nights [approximately Week 1]), Months 1, 3 and 6

ID	Title	Description
OG000	Placebo	Participants received lemborexant-matched placebo, tablet, orally, once daily for up to Month 6 in the placebo-controlled treatment period. Then they were re-randomized to lemborexant 5 mg or lemborexant 10 mg up to Month 12.
OG001	Lemborexant 5 mg	Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).

Secondary

Change From Baseline in Subjective Wake After Sleep Onset (sWASO) at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6

sWASO was defined as sum of estimated minutes of wake during the night after initial sleep onset until the time the participant stopped trying to sleep for the night, operationalized as the time the participant got out of bed for the day.

Posted

Mean

Standard Deviation

minutes

Baseline, (mean of 7 nights [approximately Week 1]), Months 1, 3 and 6

ID	Title	Description
OG000	Placebo	Participants received lemborexant-matched placebo, tablet, orally, once daily for up to Month 6 in the placebo-controlled treatment period. Then they were re-randomized to lemborexant 5 mg or lemborexant 10 mg up to Month 12.
OG001	Lemborexant 5 mg	Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).
OG002	Lemborexant 10 mg

Secondary

Change From Baseline in sTST at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6

sTST was defined as minutes of sleep from sleep onset to time stopped trying to sleep for the night.

Posted

Mean

Standard Deviation

minutes

Baseline, (mean of 7 nights [approximately Week 1]), Months 1, 3 and 6

ID	Title	Description
OG000	Placebo	Participants received lemborexant-matched placebo, tablet, orally, once daily for up to Month 6 in the placebo-controlled treatment period. Then they were re-randomized to lemborexant 5 mg or lemborexant 10 mg up to Month 12.
OG001	Lemborexant 5 mg	Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).
OG002	Lemborexant 10 mg	Participants received lemborexant 10 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).

Secondary

Percentage of Sleep Onset Responders and Sleep Maintenance Responders at Month 6

Sleep onset responder was defined as follows: sSOL at study Baseline was greater than or equal to (>=) 30 minutes and mean sSOL at 6 months was less than or equal to (<=) 20 minutes. Sleep maintenance responder was defined as follows: sWASO at study Baseline was >=60 minutes and mean sWASO at 6 months was <=60 minutes and showed a reduction of greater than (>)10 minutes compared to Study Baseline.

The FAS was the group of randomized participants who received at least one dose of randomized study drug and had at least one postdose primary efficacy measurement. Number analyzed refers to number of participants evaluable for specified category.

Posted

Number

percentage of responders

Month 6

ID	Title	Description
OG000	Placebo	Participants received lemborexant-matched placebo, tablet, orally, once daily for up to Month 6 in the placebo-controlled treatment period. Then they were re-randomized to lemborexant 5 mg or lemborexant 10 mg up to Month 12.
OG001	Lemborexant 5 mg	Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).
OG002	Lemborexant 10 mg

Secondary

Percentage of Sleep Onset Responders and Sleep Maintenance Responders at Month 12

Sleep onset responder was defined as follows: sSOL at study Baseline was >=30 minutes and mean sSOL at 6 months was <=20 minutes. Sleep maintenance responder was defined as follows: sWASO at study Baseline was >=60 minutes and mean sWASO at 6 months was <=60 minutes and showed a reduction of > 10 minutes compared to study Baseline.

Overall participants analyzed based on number in "On-Treatment FAS (Participants who received at least 1 dose of lemborexant and had at least 1 postdose primary efficacy measurement)". Hence, these numbers include lemborexant data from participants re-randomized from placebo in Period 1. Number analyzed=participants analyzed at specified timepoint.

Posted

Number

percentage of participants

Month 12

ID	Title	Description
OG000	Lemborexant 5 mg	Participants received lemborexant 5 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 5 mg, tablets, orally, once daily through Month 7-12 (in Period 2).
OG001	Lemborexant 10 mg	Participants received lemborexant 10 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 10 mg, tablets, orally, once daily through Month 7-12 (in Period 2).

Secondary

Change From Baseline in Insomnia Severity Index (ISI) Daytime Functioning Score at Months 1, 3, and 6

The ISI is a 4-7 item, self-report questionnaire assessing the nature, severity, and impact of insomnia. The dimensions evaluated were: 1. severity of sleep onset; 2. sleep maintenance; 3. early morning awakening problems; 4. sleep dissatisfaction; 5. interference of sleep difficulties with daytime functioning; 6. noticeability of the sleep problems by others; and 7. distress caused by the sleep difficulties. A 5-point Likert scale was used to rate each item (from 0=no problem to 4=very severe problem). Daytime functioning score (sum of items 4 to 7) were analyzed. Higher score indicated severe insomnia problem. The total score range for sum of items is 0-16.

Posted

Mean

Standard Deviation

score on a scale

Baseline, Months 1, 3, and 6

ID	Title	Description
OG000	Placebo	Participants received lemborexant-matched placebo, tablet, orally, once daily for up to Month 6 in the placebo-controlled treatment period. Then they were re-randomized to Lemborexant 5 mg or Lemborexant 10 mg.
OG001	Lemborexant 5 mg	Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).

Secondary

Change From Baseline in Fatigue Severity Scale (FSS) Total Score at Months 1, 3 and 6

The FSS is a self-reported scale on which participants were instructed to choose a number from 1 to 7 that indicated their degree of agreement with 9 statements about their fatigue where "1" indicates strongly disagree and "7", strongly agree. The FSS total score was the sum of all responses to the 9 questions. Higher total scores and average item scores indicated greater fatigue. Total score range is 9 to 63.

Posted

Mean

Standard Deviation

score on a scale

Baseline, Months 1, 3 and 6

ID	Title	Description
OG000	Placebo	Participants received lemborexant-matched placebo, tablet, orally, once daily for up to Month 6 in the placebo-controlled treatment period. Then they were re-randomized to lemborexant 5 mg or lemborexant 10 mg up to Month 12.
OG001	Lemborexant 5 mg	Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).
OG002	Lemborexant 10 mg

Secondary

Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1, 3 and 6

The Sleep Diary was used to assess subjective ratings of morning sleepiness with the following question:

"How sleepy/alert do you feel this morning?" Participants rated their sleepiness/alertness level on a scale from 1 to 9, with 1 being extremely poor (sleepy) and 9 being extremely good (alert). Higher score indicated better outcome.

Posted

Mean

Standard Deviation

score on a scale

Baseline, (mean of 7 nights [approximately Week 1]) in placebo-controlled period, Month 1, 3, 6

ID	Title	Description
OG000	Placebo	Participants received lemborexant-matched placebo, tablet, orally, once daily for up to Month 6 in the placebo-controlled treatment period. Then they were re-randomized to lemborexant 5 mg or lemborexant 10 mg up to Month 12.
OG001	Lemborexant 5 mg	Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).

Secondary

Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Active Treatment Period)

Posted

Mean

Standard Deviation

score on a scale

Baseline, First 7 nights (approximately Week 1) in active treatment period

ID	Title	Description
OG000	Lemborexant 5 mg	Participants received lemborexant 5 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 5 mg, tablets, orally, once daily through Month 7-12 (in Period 2).
OG001	Lemborexant 10 mg	Participants received lemborexant 10 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 10 mg, tablets, orally, once daily through Month 7-12 (in Period 2).

Units	Counts
Participants

Secondary

Change From Screening in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at the First and Second 7 Mornings of the Follow-up Period

The Sleep Diary was used to assess subjective ratings of morning sleepiness with the following question:

Posted

Mean

Standard Deviation

score on a scale

Screening, First and second 7 mornings in follow-up period (Week 52 to 54)

ID	Title	Description
OG000	Lemborexant 5 mg	Participants received lemborexant 5 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 5 mg, tablets, orally, once daily through Month 7-12 (in Period 2).
OG001	Lemborexant 10 mg	Participants received lemborexant 10 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 10 mg, tablets, orally, once daily through Month 7-12 (in Period 2).

Secondary

Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at Months 1, 3, 6, 9 and 12

The Sleep Diary was used to assess subjective ratings of morning sleepiness with the following question:

Posted

Mean

Standard Deviation

score on a scale

Baseline, Months 1, 3, 6, 9 and 12

ID	Title	Description
OG000	Lemborexant 5 mg	Participants received lemborexant 5 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 5 mg, tablets, orally, once daily through Month 7-12 (in Period 2).
OG001	Lemborexant 10 mg	Participants received lemborexant 10 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 10 mg, tablets, orally, once daily through Month 7-12 (in Period 2).

Secondary

Rebound Insomnia: Mean sSOL on Each of the First 3 Nights, First 7 Nights, and Last 7 Nights of the Follow-up Period

Rebound Insomnia: Rebound insomnia was defined as insomnia that occurred following discontinuation of a sedative substance taken to relieve primary insomnia. sSOL was defined as estimated minutes from the time that the participant attempted to sleep until sleep onset.

Posted

Mean

Standard Deviation

minutes

First 3 nights, first and Last 7 nights of the follow up period (Week 52 to 54)

ID	Title	Description
OG000	Lemborexant 5 mg	Participants received lemborexant 5 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 5 mg, tablets, orally, once daily through Month 7-12 (in Period 2).
OG001	Lemborexant 10 mg	Participants received lemborexant 10 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 10 mg, tablets, orally, once daily through Month 7-12 (in Period 2).

Secondary

Rebound Insomnia: Mean sWASO on Each of the First 3 Nights, First 7 Nights, and Last 7 Nights of the Follow-up Period

Rebound Insomnia: Rebound insomnia was defined as insomnia that occurred following discontinuation of a sedative substance taken to relieve primary insomnia. sWASO was defined as sum of estimated minutes of wake during the night after initial sleep onset until the time the participant stopped trying to sleep for the night, operationalized as the time the participant got out of bed for the day.

Posted

Mean

Standard Deviation

minutes

First 3 nights, first and last 7 nights of the follow up period (Week 52 to 54)

ID	Title	Description
OG000	Lemborexant 5 mg	Participants received lemborexant 5 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 5 mg, tablets, orally, once daily through Month 7-12 (in Period 2).
OG001	Lemborexant 10 mg	Participants received lemborexant 10 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 10 mg, tablets, orally, once daily through Month 7-12 (in Period 2).

Secondary

Rebound Insomnia: Percentage of Participants Whose sSOL Was Longer Than at Screening for First 3 Nights of the Follow-up Period, or Whom Mean sSOL Was Longer Than at Screening for First 7 Nights or Last 7 Nights of the Follow-up Period

Posted

Number

percentage of participants

First 3 nights, first and last 7 nights of the follow up period (Week 52 to 54)

ID	Title	Description
OG000	Lemborexant 5 mg	Participants received lemborexant 5 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 5 mg, tablets, orally, once daily through Month 7-12 (in Period 2).
OG001	Lemborexant 10 mg	Participants received lemborexant 10 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 10 mg, tablets, orally, once daily through Month 7-12 (in Period 2).

Secondary

Rebound Insomnia: Percentage of Participants Whose sWASO is Higher Than at Screening for First 3 Nights of the Follow-up Period, or Whose Mean sWASO is Higher Than at Screening for the First 7 Nights or Last 7 Nights of the Follow-up Period

Posted

Number

percentage of participants

First 3 nights, First and Last 7 nights of the follow up period (Week 52 to 54)

ID	Title	Description
OG000	Lemborexant 5 mg	Participants received lemborexant 5 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 5 mg, tablets, orally, once daily through Month 7-12 (in Period 2).
OG001	Lemborexant 10 mg	Participants received lemborexant 10 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 10 mg, tablets, orally, once daily through Month 7-12 (in Period 2).

Secondary

Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1

sSOL was defined as estimated minutes from the time that the participant attempted to sleep until sleep onset. sWASO was defined as sum of estimated minutes of wake during the night after initial sleep onset until the time the participant stopped trying to sleep for the night, operationalized as the time the participant got out of bed for the day. sTST: minutes of sleep from sleep onset to time stopped trying to sleep for the night. At each month beyond Month 1, the change from Baseline was compared to either the lower bound of the 95% CI (for sTST) or the upper bound of the 95% CI (for sSOL and sWASO) at Month 1. Persistence of efficacy was defined as present if the mean change from Baseline at Month 6 was above the lower bound of the 95% CI at Month 1 for sTST and below the upper bound of the 95% CI at Month 1 for sSOL and sWASO.

Posted

Least Squares Mean

95% Confidence Interval

minutes

Baseline, Month 1, 3, 6, 9, 12

ID	Title	Description
OG000	Lemborexant 5 mg	Participants received lemborexant 5 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 5 mg, tablets, orally, once daily through Month 7-12 (in Period 2).

Secondary

Persistence of Effect: Mean Change From Baseline in sSE at Months 3, 6, 9, and 12 Compared to Month 1

sSE was defined as percentage of sTST per subjective time spent in bed, calculated as the interval from the time the participant reports attempting to sleep until the time the participant stopped trying to sleep for the night (operationalized as the time the participant got out of bed for the day), and time spent asleep derived from subjective time spent in bed minus sWASO. At each month beyond Month 1, the change from Baseline was compared to the lower bound of the 95% CI at Month 1. Persistence of efficacy was defined as present if the mean change from Baseline at Month 6 was above the lower bound of the 95% CI at Month 1 for sSE.

Posted

Least Squares Mean

95% Confidence Interval

percentage of sTST

Baseline, Months 1, 3, 6, 9, and 12

ID	Title	Description
OG000	Lemborexant 5 mg	Participants received lemborexant 5 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 5 mg, tablets, orally, once daily through Month 7-12 (in Period 2).
OG001	Lemborexant 10 mg

Secondary

Persistence of Effect: Mean Change From Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 9 and 12 Compared to Month 7

sSOL is defined as estimated minutes from the time that the participant attempted to sleep until sleep onset. sWASO: sum of estimated minutes of wake during the night after initial sleep onset until the time the participant stopped trying to sleep for the night, operationalized as the time the participant got out of bed for the day. sTST: minutes of sleep from sleep onset to time stopped trying to sleep for the night. At each month beyond Month 7, the change from Baseline was compared to either the lower bound of the 95% CI for sTST or the upper bound of the 95% CI (for sSOL and sWASO) at Month 7. Persistence of effect was defined as present if the mean change from Baseline at Month 12 was above the lower bound of the 95% CI at Month 7 for sTST and below the upper bound of the 95% CI at Month 7 for sSOL and sWASO.

Posted

Least Squares Mean

95% Confidence Interval

minutes

Baseline, Month 7, 9, 12

ID	Title	Description
OG000	Lemborexant 5 mg	Participants received lemborexant 5 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 5 mg, tablets, orally, once daily through Month 7-12 (in Period 2).

Secondary

Persistence of Effect: Mean Change From Period 2 Baseline (Month 6) in sSE at Months 9 and 12 Compared to Month 7

sSE: percentage of sTST per subjective time spent in bed, calculated as the interval from the time the participant reports attempting to sleep until the time the participant stopped trying to sleep for the night (operationalized as the time the subject got out of bed for the day), and time spent asleep derived from subjective time spent in bed minus sWASO. At each month beyond Month 7, the change from Baseline was compared to the lower bound of the 95% CI for sSE at Month 7. Persistence of effect was defined as present if the mean change from Baseline at Month 12 was above the lower bound of the 95% CI at Month 7 for sSE.

Posted

Least Squares Mean

95% Confidence Interval

percentage of sTST

Baseline, Month 7, 9, 12

ID	Title	Description
OG000	Lemborexant 5 mg	Participants received lemborexant 5 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 5 mg, tablets, orally, once daily through Month 7-12 (in Period 2).
OG001	Lemborexant 10 mg

Secondary

Persistence of Effect: Mean Change From Study Baseline and Period 2 Baseline (Month 6) in sSOL, sWASO, and sTST at Months 3 and 6 Exposure Compared to Month 1

sSOL was defined as estimated minutes from the time that the participant attempted to sleep until sleep onset. sWASO: sum of estimated minutes of wake during the night after initial sleep onset until the time the participant stopped trying to sleep for the night, operationalized as the time the participant got out of bed for the day. sTST: minutes of sleep from sleep onset to time stopped trying to sleep for the night. At 3 and 6 months of exposure, the change from Baseline was compared to either the lower bound of the 95% CI for sTST or the upper bound of the 95% CI (for sSOL and sWASO) at 1 month of exposure. Persistence of effect was defined as present if the mean change from Baseline at 6 months of exposure was above the lower bound of the 95% CI at 1 month of exposure for sTST and below the upper bound of the 95% CI at 1 month of exposure for sSOL and sWASO.

Posted

Least Squares Mean

95% Confidence Interval

minutes

Baseline, Month 1, 3, 6

ID	Title	Description
OG000	Lemborexant 5 mg	Participants received lemborexant 5 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 5 mg, tablets, orally, once daily through Month 7-12 (in Period 2).

Secondary

Persistence of Effect: Mean Change From Study Baseline and Period 2 Baseline (Month 6) in sSE at Months 3 and 6 Exposure Compared to Month 1

sSE was defined as percentage of sTST per subjective time spent in bed, calculated as the interval from the time the participant reports attempting to sleep until the time the participant stopped trying to sleep for the night (operationalized as the time the participant got out of bed for the day), and time spent asleep derived from subjective time spent in bed minus sWASO. At 3 and 6 months of exposure, the change from Baseline was compared to the lower bound of the 95% CI for sSE at 1 month of exposure. Persistence of effect was defined as present if the mean change from Baseline at 6 months of exposure was above the lower bound of the 95% CI at 1 month of exposure for sSE.

On-treatment FAS was the group of participants who received at least 1 dose of lemborexant and had at least 1 post dose primary efficacy measurement. Overall Participants Analyzed here is based on the number in the "On-Treatment FAS". Hence these numbers include the lemborexant data from the participants re-randomized from placebo in Period 1.

Posted

Least Squares Mean

95% Confidence Interval

percentage of sTST

Baseline, Month 1, 3, 6

ID	Title	Description
OG000	Lemborexant 5 mg	Participants received lemborexant 5 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 5 mg, tablets, orally, once daily through Month 7-12 (in Period 2).
OG001	Lemborexant 10 mg

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Angina Pectoris	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0011 events1 affected447 at risk EG0020 events0 affected437 at risk
Goitre	Endocrine disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected319 at risk EG0010 events0 affected447 at risk EG0020 events0 affected437 at risk
Diabetic Retinopathy	Eye disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0011 events1 affected447 at risk EG0020 events0 affected437 at risk
Chest Pain	General disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0011 events1 affected447 at risk EG0020 events0 affected437 at risk
Cyst	General disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected319 at risk EG0010 events0 affected447 at risk EG0020 events0 affected437 at risk
Cholestasis	Hepatobiliary disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0010 events0 affected447 at risk EG0021 events1 affected437 at risk
Hepatotoxicity	Hepatobiliary disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0010 events0 affected447 at risk EG0021 events1 affected437 at risk
Cystitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0010 events0 affected447 at risk EG0021 events1 affected437 at risk
Pneumonia	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected319 at risk EG0011 events1 affected447 at risk EG0020 events0 affected437 at risk
Postoperative Wound Infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0011 events1 affected447 at risk EG0020 events0 affected437 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0011 events1 affected447 at risk EG0021 events1 affected437 at risk
Lower Limb Fracture	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0011 events1 affected447 at risk EG0020 events0 affected437 at risk
Pelvic Fracture	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected319 at risk EG0010 events0 affected447 at risk EG0020 events0 affected437 at risk
Rib Fracture	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected319 at risk EG0010 events0 affected447 at risk EG0021 events1 affected437 at risk
Tibia Fracture	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected319 at risk EG0010 events0 affected447 at risk EG0020 events0 affected437 at risk
Type 2 Diabetes Mellitus	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0010 events0 affected447 at risk EG0021 events1 affected437 at risk
Jaw Cyst	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected319 at risk EG0010 events0 affected447 at risk EG0020 events0 affected437 at risk
Jaw Fistula	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected319 at risk EG0010 events0 affected447 at risk EG0020 events0 affected437 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0011 events1 affected447 at risk EG0023 events3 affected437 at risk
Intraductal Proliferative Breast Lesion	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0010 events0 affected447 at risk EG0021 events1 affected437 at risk
Cerebrovascular Accident	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0010 events0 affected447 at risk EG0021 events1 affected437 at risk
Diabetic Neuropathy	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0012 events2 affected447 at risk EG0020 events0 affected437 at risk
Disturbance In Attention	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0010 events0 affected447 at risk EG0021 events1 affected437 at risk
Hydrosalpinx	Reproductive system and breast disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0011 events1 affected447 at risk EG0020 events0 affected437 at risk
Chronic Obstructive Pulmonary Disease	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0010 events0 affected447 at risk EG0021 events1 affected437 at risk
Deep Vein Thrombosis	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0010 events0 affected447 at risk EG0021 events1 affected437 at risk
Hypertension	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0011 events1 affected447 at risk EG0020 events0 affected437 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0010 events0 affected447 at risk EG0021 events1 affected437 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0011 events1 affected447 at risk EG0020 events0 affected437 at risk
Extrasystoles	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0010 events0 affected447 at risk EG0021 events1 affected437 at risk
Floppy eyelid syndrome	Eye disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0011 events1 affected447 at risk EG0020 events0 affected437 at risk
Alcoholic pancreatitis	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0011 events1 affected447 at risk EG0020 events0 affected437 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0010 events0 affected447 at risk EG0021 events1 affected437 at risk
Gastrointestinal inflammation	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0011 events1 affected447 at risk EG0020 events0 affected437 at risk
Hiatus hernia	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0011 events1 affected447 at risk EG0020 events0 affected437 at risk
Inflammation	General disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0011 events1 affected447 at risk EG0020 events0 affected437 at risk
Non-cardiac chest pain	General disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0011 events1 affected447 at risk EG0020 events0 affected437 at risk
Erysipelas	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0011 events1 affected447 at risk EG0020 events0 affected437 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0011 events1 affected447 at risk EG0021 events1 affected437 at risk
Hand fracture	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0011 events1 affected447 at risk EG0020 events0 affected437 at risk
Meniscus injury	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0010 events0 affected447 at risk EG0021 events1 affected437 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0011 events1 affected447 at risk EG0020 events0 affected437 at risk
Intentional Overdose	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0017 events1 affected447 at risk EG0020 events0 affected437 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0010 events0 affected447 at risk EG0021 events1 affected437 at risk
Laryngeal Inflammation	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0010 events0 affected447 at risk EG0021 events1 affected437 at risk
Dermal Cyst	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected319 at risk EG0011 events1 affected447 at risk EG0020 events0 affected437 at risk

ID	Term
D020919	Sleep Disorders, Intrinsic
D020920	Dyssomnias
D012893	Sleep Wake Disorders
D009422	Nervous System Diseases
D001523	Mental Disorders

ID	Title	Description
BG000	Placebo	Participants received lemborexant-matched placebo, tablet, orally, once daily for up to Month 6 in the placebo-controlled treatment period. Then they were re-randomized to lemborexant 5 mg or lemborexant 10 mg up to Month 12.
BG001	Lemborexant 5 mg	Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).
BG002	Lemborexant 10 mg	Participants received lemborexant 10 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Participants received placebo matched to lemborexant tablet, orally, once daily for up to 6 months. Then they were re-randomized to Lemborexant 5 mg or Lemborexant 10 mg.	319	5	319	75	319
EG001	Lemborexant 5 mg	Participants received lemborexant 5 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 5 mg, tablets, orally, once daily through Month 7-12 (in Period 2).	447	18	447	129	447
EG002	Lemborexant 10 mg	Participants received lemborexant 10 mg/placebo, tablets, orally, once daily through Month 1-6 (in Period 1) and lemborexant 10 mg, tablets, orally, once daily through Month 7-12 (in Period 2).	437	16	437	140	437

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Influenza	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG00015 events15 affected319 at risk EG00122 events22 affected447 at risk EG00229 events26 affected437 at risk
Nasopharyngitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG00043 events40 affected319 at risk EG00167 events51 affected447 at risk EG00256 events48 affected437 at risk
Headache	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG00033 events21 affected319 at risk EG00176 events43 affected447 at risk EG00241 events32 affected437 at risk
Somnolence	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0005 events5 affected319 at risk EG00144 events38 affected447 at risk EG00264 events60 affected437 at risk