Trial Outcomes & Findings for Long-term Study of Lemborexant in Insomnia Disorder (SUNRISE 2) (NCT NCT02952820)

NCT ID: NCT02952820

Last Updated: 2020-02-06

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

971 participants

Primary outcome timeframe

Baseline and Month 6

Results posted on

2020-02-06

Participant Flow

Participants took part in the study at 119 investigative sites in Japan, Korea, Finland, Germany, Italy, New Zealand, Poland, Romania, Spain, Canada, Mexico, and the United States from 15 November 2016 to 08 January 2019.

A total of 2059 participants were screened, of which 1088 were screen failures and 971 participants were randomized to receive study treatment.

Participant milestones

Participant milestones
Measure	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.	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).	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).
Placebo-Controlled Treatment (6 Months) STARTED	325	323	323
Placebo-Controlled Treatment (6 Months) Treated	321	319	319
Placebo-Controlled Treatment (6 Months) Safety Analysis Set	319	314	314
Placebo-Controlled Treatment (6 Months) COMPLETED	261	254	235
Placebo-Controlled Treatment (6 Months) NOT COMPLETED	64	69	88
Active Treatment Period (6 Months) STARTED	0	384	352
Active Treatment Period (6 Months) COMPLETED	0	346	321
Active Treatment Period (6 Months) NOT COMPLETED	0	38	31

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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).	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).
Placebo-Controlled Treatment (6 Months) Adverse Event	8	9	16
Placebo-Controlled Treatment (6 Months) Lost to Follow-up	7	7	6
Placebo-Controlled Treatment (6 Months) Subject choice	15	12	17
Placebo-Controlled Treatment (6 Months) Inadequate therapeutic effect	17	12	11
Placebo-Controlled Treatment (6 Months) Other than specified	0	14	13
Placebo-Controlled Treatment (6 Months) Withdrawal of consent	13	11	21
Placebo-Controlled Treatment (6 Months) Not treated	4	4	4
Active Treatment Period (6 Months) Adverse Event	0	6	5
Active Treatment Period (6 Months) Lost to Follow-up	0	4	6
Active Treatment Period (6 Months) Subject choice	0	10	7
Active Treatment Period (6 Months) Inadequate therapeutic effect	0	6	2
Active Treatment Period (6 Months) Withdrawal of consent	0	6	8
Active Treatment Period (6 Months) Other than specified	0	6	2
Active Treatment Period (6 Months) Not treated	0	0	1

Baseline Characteristics

Long-term Study of Lemborexant in Insomnia Disorder (SUNRISE 2)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=318 Participants 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.	Lemborexant 5 mg n=316 Participants Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).	Lemborexant 10 mg n=315 Participants Participants received lemborexant 10 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).	Total n=949 Participants Total of all reporting groups
Age, Continuous	54.5 years STANDARD_DEVIATION 14.01 • n=5 Participants	54.2 years STANDARD_DEVIATION 13.74 • n=7 Participants	54.8 years STANDARD_DEVIATION 13.68 • n=5 Participants	54.5 years STANDARD_DEVIATION 13.80 • n=4 Participants
Sex: Female, Male Female	216 Participants n=5 Participants	209 Participants n=7 Participants	222 Participants n=5 Participants	647 Participants n=4 Participants
Sex: Female, Male Male	102 Participants n=5 Participants	107 Participants n=7 Participants	93 Participants n=5 Participants	302 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	34 Participants n=5 Participants	19 Participants n=7 Participants	19 Participants n=5 Participants	72 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	284 Participants n=5 Participants	297 Participants n=7 Participants	296 Participants n=5 Participants	877 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized White	232 Participants n=5 Participants	222 Participants n=7 Participants	225 Participants n=5 Participants	679 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	23 Participants n=5 Participants	27 Participants n=7 Participants	26 Participants n=5 Participants	76 Participants n=4 Participants
Race/Ethnicity, Customized Japanese	54 Participants n=5 Participants	53 Participants n=7 Participants	54 Participants n=5 Participants	161 Participants n=4 Participants
Race/Ethnicity, Customized Chinese	0 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Race/Ethnicity, Customized Other Asian	5 Participants n=5 Participants	5 Participants n=7 Participants	3 Participants n=5 Participants	13 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Other	4 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	12 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Month 6

Population: 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.

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

Outcome measures

Outcome measures
Measure	Placebo n=318 Participants 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.	Lemborexant 5 mg n=316 Participants Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).	Lemborexant 10 mg n=315 Participants Participants received lemborexant 10 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).
Change From Baseline in Subjective Sleep Onset Latency (sSOL) at Month 6 Baseline	64.03 minutes Standard Deviation 45.209	62.19 minutes Standard Deviation 45.674	64.97 minutes Standard Deviation 44.020
Change From Baseline in Subjective Sleep Onset Latency (sSOL) at Month 6 Change at Month 6	-16.57 minutes Standard Deviation 35.313	-29.39 minutes Standard Deviation 33.261	-32.49 minutes Standard Deviation 35.962

SECONDARY outcome

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

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

Outcome measures

Outcome measures
Measure	Placebo n=318 Participants 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.	Lemborexant 5 mg n=316 Participants Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).	Lemborexant 10 mg n=315 Participants Participants received lemborexant 10 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).
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 Change at Month 1	-11.48 minutes Standard Deviation 32.726	-19.41 minutes Standard Deviation 32.221	-24.06 minutes Standard Deviation 35.234
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 Baseline	64.03 minutes Standard Deviation 45.209	62.19 minutes Standard Deviation 45.674	64.97 minutes Standard Deviation 44.020
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 Change at 1st 7 nights	-4.11 minutes Standard Deviation 27.671	-16.86 minutes Standard Deviation 27.784	-18.89 minutes Standard Deviation 31.003
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 Change at Month 3	-13.84 minutes Standard Deviation 35.277	-25.08 minutes Standard Deviation 34.081	-27.94 minutes Standard Deviation 39.192

SECONDARY outcome

Timeframe: Baseline, (mean of 7 nights [approximately Week 1]), 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.

Outcome measures

Outcome measures
Measure	Placebo n=318 Participants 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.	Lemborexant 5 mg n=316 Participants Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).	Lemborexant 10 mg n=315 Participants Participants received lemborexant 10 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).
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 Baseline	61.34 percentage of sTST Standard Deviation 17.836	63.14 percentage of sTST Standard Deviation 18.231	62.03 percentage of sTST Standard Deviation 17.248
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 Change at 1st 7 nights	2.68 percentage of sTST Standard Deviation 10.765	6.61 percentage of sTST Standard Deviation 10.386	8.27 percentage of sTST Standard Deviation 10.566
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 Change at Month 1	6.11 percentage of sTST Standard Deviation 12.876	7.87 percentage of sTST Standard Deviation 12.263	9.92 percentage of sTST Standard Deviation 12.922
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 Change at Month 3	9.16 percentage of sTST Standard Deviation 13.644	13.03 percentage of sTST Standard Deviation 13.522	13.61 percentage of sTST Standard Deviation 14.035
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 Change at Month 6	10.36 percentage of sTST Standard Deviation 13.799	15.34 percentage of sTST Standard Deviation 14.613	15.55 percentage of sTST Standard Deviation 15.617

SECONDARY outcome

Timeframe: Baseline, (mean of 7 nights [approximately Week 1]), 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.

Outcome measures

Outcome measures
Measure	Placebo n=318 Participants 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.	Lemborexant 5 mg n=316 Participants Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).	Lemborexant 10 mg n=315 Participants Participants received lemborexant 10 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).
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 Change at Month 3	-27.08 minutes Standard Deviation 54.408	-42.98 minutes Standard Deviation 60.064	-39.42 minutes Standard Deviation 62.783
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 Change at Month 6	-32.14 minutes Standard Deviation 55.279	-51.45 minutes Standard Deviation 67.295	-48.12 minutes Standard Deviation 68.550
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 Baseline	132.49 minutes Standard Deviation 80.198	132.77 minutes Standard Deviation 82.518	136.83 minutes Standard Deviation 87.391
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 Change at first 7 nights	-6.12 minutes Standard Deviation 45.893	-20.21 minutes Standard Deviation 46.015	-23.30 minutes Standard Deviation 47.700
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 Change at Month 1	-19.01 minutes Standard Deviation 50.279	-23.42 minutes Standard Deviation 56.251	-26.82 minutes Standard Deviation 56.989

SECONDARY outcome

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

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

Outcome measures

Outcome measures
Measure	Placebo n=318 Participants 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.	Lemborexant 5 mg n=316 Participants Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).	Lemborexant 10 mg n=315 Participants Participants received lemborexant 10 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).
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 Baseline	304.25 minutes Standard Deviation 91.459	315.52 minutes Standard Deviation 93.498	306.89 minutes Standard Deviation 88.031
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 Change at first 7 nights	14.78 minutes Standard Deviation 54.995	34.29 minutes Standard Deviation 54.142	46.01 minutes Standard Deviation 55.110
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 Change at Month 1	30.74 minutes Standard Deviation 70.687	39.32 minutes Standard Deviation 63.548	53.22 minutes Standard Deviation 67.910
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 Change at Month 3	48.16 minutes Standard Deviation 75.859	65.82 minutes Standard Deviation 71.331	70.95 minutes Standard Deviation 70.913
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 Change at Month 6	53.53 minutes Standard Deviation 74.539	76.21 minutes Standard Deviation 77.714	78.32 minutes Standard Deviation 80.741

SECONDARY outcome

Timeframe: Month 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=318 Participants 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.	Lemborexant 5 mg n=316 Participants Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).	Lemborexant 10 mg n=315 Participants Participants received lemborexant 10 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).
Percentage of Sleep Onset Responders and Sleep Maintenance Responders at Month 6 Sleep Maintenance Responders	20.4 percentage of responders	35.0 percentage of responders	30.0 percentage of responders
Percentage of Sleep Onset Responders and Sleep Maintenance Responders at Month 6 Sleep Onset Responders	17.7 percentage of responders	31.2 percentage of responders	30.1 percentage of responders

SECONDARY outcome

Timeframe: Month 12

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=444 Participants 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.	Lemborexant 5 mg n=437 Participants Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).	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).
Percentage of Sleep Onset Responders and Sleep Maintenance Responders at Month 12 Sleep Onset Responders	34.2 percentage of participants	37.2 percentage of participants	—
Percentage of Sleep Onset Responders and Sleep Maintenance Responders at Month 12 Sleep Maintainance Responders	35.0 percentage of participants	39.6 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline, 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.

Outcome measures

Outcome measures
Measure	Placebo n=318 Participants 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.	Lemborexant 5 mg n=316 Participants Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).	Lemborexant 10 mg n=315 Participants Participants received lemborexant 10 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).
Change From Baseline in Insomnia Severity Index (ISI) Daytime Functioning Score at Months 1, 3, and 6 Baseline	11.0 score on a scale Standard Deviation 2.10	11.4 score on a scale Standard Deviation 2.02	11.0 score on a scale Standard Deviation 2.15
Change From Baseline in Insomnia Severity Index (ISI) Daytime Functioning Score at Months 1, 3, and 6 Change at Month 1	-3.1 score on a scale Standard Deviation 3.41	-4.1 score on a scale Standard Deviation 3.66	-4.2 score on a scale Standard Deviation 4.01
Change From Baseline in Insomnia Severity Index (ISI) Daytime Functioning Score at Months 1, 3, and 6 Change at Month 6	-4.3 score on a scale Standard Deviation 3.66	-6.0 score on a scale Standard Deviation 3.76	-5.7 score on a scale Standard Deviation 4.00
Change From Baseline in Insomnia Severity Index (ISI) Daytime Functioning Score at Months 1, 3, and 6 Change at Month 3	-3.7 score on a scale Standard Deviation 3.55	-5.2 score on a scale Standard Deviation 3.88	-5.2 score on a scale Standard Deviation 4.05

SECONDARY outcome

Timeframe: Baseline, 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.

Outcome measures

Outcome measures
Measure	Placebo n=318 Participants 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.	Lemborexant 5 mg n=316 Participants Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).	Lemborexant 10 mg n=315 Participants Participants received lemborexant 10 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).
Change From Baseline in Fatigue Severity Scale (FSS) Total Score at Months 1, 3 and 6 Baseline	35.2 score on a scale Standard Deviation 13.55	37.4 score on a scale Standard Deviation 12.74	36.0 score on a scale Standard Deviation 13.01
Change From Baseline in Fatigue Severity Scale (FSS) Total Score at Months 1, 3 and 6 Change at Month 1	-3.9 score on a scale Standard Deviation 11.62	-6.6 score on a scale Standard Deviation 11.83	-6.4 score on a scale Standard Deviation 13.68
Change From Baseline in Fatigue Severity Scale (FSS) Total Score at Months 1, 3 and 6 Change at Month 3	-4.3 score on a scale Standard Deviation 11.37	-7.7 score on a scale Standard Deviation 12.97	-7.9 score on a scale Standard Deviation 13.56
Change From Baseline in Fatigue Severity Scale (FSS) Total Score at Months 1, 3 and 6 Change at Month 6	-6.3 score on a scale Standard Deviation 12.07	-10.1 score on a scale Standard Deviation 13.56	-8.9 score on a scale Standard Deviation 14.91

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Placebo n=318 Participants 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.	Lemborexant 5 mg n=316 Participants Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).	Lemborexant 10 mg n=315 Participants Participants received lemborexant 10 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).
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 Baseline	3.94 score on a scale Standard Deviation 1.558	3.93 score on a scale Standard Deviation 1.349	3.93 score on a scale Standard Deviation 1.324
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 Change at First 7 nights	0.15 score on a scale Standard Deviation 0.991	0.36 score on a scale Standard Deviation 0.964	0.33 score on a scale Standard Deviation 1.018
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 Change at Month 1	0.44 score on a scale Standard Deviation 1.233	0.53 score on a scale Standard Deviation 1.172	0.55 score on a scale Standard Deviation 1.298
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 Change at Month 3	0.62 score on a scale Standard Deviation 1.366	0.74 score on a scale Standard Deviation 1.325	0.90 score on a scale Standard Deviation 1.452
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 Change at Month 6	0.79 score on a scale Standard Deviation 1.392	0.98 score on a scale Standard Deviation 1.463	1.05 score on a scale Standard Deviation 1.524

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Placebo n=444 Participants 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.	Lemborexant 5 mg n=437 Participants Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).	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).
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) Change at First 7 nights	0.36 score on a scale Standard Deviation 0.964	0.33 score on a scale Standard Deviation 1.018	—
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) Baseline	4.15 score on a scale Standard Deviation 1.516	4.16 score on a scale Standard Deviation 1.428	—

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Placebo n=444 Participants 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.	Lemborexant 5 mg n=437 Participants Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).	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).
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 Screening	3.63 score on a scale Standard Deviation 1.393	3.54 score on a scale Standard Deviation 1.197	—
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 Change at First 7 mornings	1.03 score on a scale Standard Deviation 1.615	1.32 score on a scale Standard Deviation 1.611	—
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 Change at Second 7 mornings	0.98 score on a scale Standard Deviation 1.699	1.22 score on a scale Standard Deviation 1.635	—

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Placebo n=444 Participants 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.	Lemborexant 5 mg n=437 Participants Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).	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).
Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at Months 1, 3, 6, 9 and 12 Baseline	4.15 score on a scale Standard Deviation 1.516	4.16 score on a scale Standard Deviation 1.428	—
Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at Months 1, 3, 6, 9 and 12 Change at Month 1 of exposure	0.46 score on a scale Standard Deviation 1.082	0.42 score on a scale Standard Deviation 1.223	—
Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at Months 1, 3, 6, 9 and 12 Change at Month 3 of exposure	0.60 score on a scale Standard Deviation 1.264	0.70 score on a scale Standard Deviation 1.356	—
Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at Months 1, 3, 6, 9 and 12 Change at Month 6 of exposure	0.78 score on a scale Standard Deviation 1.424	0.86 score on a scale Standard Deviation 1.461	—
Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at Months 1, 3, 6, 9 and 12 Change at Month 9 of exposure	1.00 score on a scale Standard Deviation 1.512	1.08 score on a scale Standard Deviation 1.489	—
Change From Baseline in Mean Rating on the Morning Sleepiness Item of the Sleep Diary at Months 1, 3, 6, 9 and 12 Change at Month 12 of exposure	1.11 score on a scale Standard Deviation 1.499	1.31 score on a scale Standard Deviation 1.604	—

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=444 Participants 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.	Lemborexant 5 mg n=437 Participants Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).	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).
Rebound Insomnia: Mean sSOL on Each of the First 3 Nights, First 7 Nights, and Last 7 Nights of the Follow-up Period Mean of first 3 nights	40.35 minutes Standard Deviation 48.661	41.73 minutes Standard Deviation 55.694	—
Rebound Insomnia: Mean sSOL on Each of the First 3 Nights, First 7 Nights, and Last 7 Nights of the Follow-up Period Mean sSOL of the first 7 nights	41.35 minutes Standard Deviation 38.967	41.90 minutes Standard Deviation 47.826	—
Rebound Insomnia: Mean sSOL on Each of the First 3 Nights, First 7 Nights, and Last 7 Nights of the Follow-up Period Mean sSOL of the second 7 nights	44.10 minutes Standard Deviation 38.030	41.30 minutes Standard Deviation 47.471	—

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=444 Participants 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.	Lemborexant 5 mg n=437 Participants Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).	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).
Rebound Insomnia: Mean sWASO on Each of the First 3 Nights, First 7 Nights, and Last 7 Nights of the Follow-up Period Mean of first 3 nights	86.66 minutes Standard Deviation 80.038	97.88 minutes Standard Deviation 83.302	—
Rebound Insomnia: Mean sWASO on Each of the First 3 Nights, First 7 Nights, and Last 7 Nights of the Follow-up Period Mean of the first 7 nights	91.56 minutes Standard Deviation 81.738	95.79 minutes Standard Deviation 79.784	—
Rebound Insomnia: Mean sWASO on Each of the First 3 Nights, First 7 Nights, and Last 7 Nights of the Follow-up Period Mean of the Last 7 nights	92.62 minutes Standard Deviation 82.672	98.19 minutes Standard Deviation 80.668	—

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Placebo n=444 Participants 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.	Lemborexant 5 mg n=437 Participants Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).	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).
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 Average of first 3 nights	9.46 percentage of participants	9.38 percentage of participants	—
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 Average of first 7 nights	11.94 percentage of participants	10.53 percentage of participants	—
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 Average of second 7 nights	11.71 percentage of participants	9.38 percentage of participants	—

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Placebo n=444 Participants 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.	Lemborexant 5 mg n=437 Participants Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).	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).
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 Average of first 3 nights	11.26 percentage of participants	12.59 percentage of participants	—
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 Average of first 7 nights	12.39 percentage of participants	14.19 percentage of participants	—
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 Average of second 7 nights	13.51 percentage of participants	11.90 percentage of participants	—

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=444 Participants 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.	Lemborexant 5 mg n=437 Participants Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).	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).
Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 sSOL: Change at Month 6 of exposure	-24.13 minutes Interval -27.22 to -21.04	-22.99 minutes Interval -26.14 to -19.83	—
Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 sSOL: Change at Month 9 of exposure	-26.00 minutes Interval -29.25 to -22.75	-27.36 minutes Interval -30.7 to -24.01	—
Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 sSOL: Change at Month 1 of exposure	-17.17 minutes Interval -19.76 to -14.58	-18.64 minutes Interval -21.26 to -16.02	—
Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 sSOL: Change at Month 3 of exposure	-21.47 minutes Interval -24.46 to -18.48	-21.58 minutes Interval -24.61 to -18.54	—
Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 sTST: Change at Month 1 of exposure	31.98 minutes Interval 25.54 to 38.42	38.04 minutes Interval 31.51 to 44.57	—
Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 sSOL: Change at Month 12 of exposure	-25.83 minutes Interval -29.44 to -22.22	-26.32 minutes Interval -30.03 to -22.61	—
Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 sWASO: Change at Month 1 of exposure	-17.26 minutes Interval -22.54 to -11.97	-18.69 minutes Interval -24.05 to -13.33	—
Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 sTST: Change at Month 3 of exposure	49.27 minutes Interval 42.33 to 56.22	53.51 minutes Interval 46.42 to 60.61	—
Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 sWASO: Change at Month 3 of exposure	-31.34 minutes Interval -37.12 to -25.57	-28.97 minutes Interval -34.86 to -23.09	—
Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 sWASO: Change at Month 6 of exposure	-36.10 minutes Interval -42.57 to -29.63	-31.54 minutes Interval -38.16 to -24.91	—
Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 sWASO: Change at Month 9 of exposure	-39.28 minutes Interval -46.74 to -31.83	-40.39 minutes Interval -48.08 to -32.71	—
Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 sWASO: Change at Month 12 of exposure	-42.87 minutes Interval -50.13 to -35.61	-43.76 minutes Interval -51.21 to -36.31	—
Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 sTST: Change at Month 6 of exposure	54.99 minutes Interval 47.18 to 62.8	56.36 minutes Interval 48.35 to 64.36	—
Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 sTST: Change at Month 9 of exposure	55.41 minutes Interval 46.49 to 64.33	61.13 minutes Interval 51.93 to 70.32	—
Persistence of Effect: Mean Change From Baseline in sSOL, sWASO, and sTST at Months 3, 6, 9, and 12 Compared to Month 1 sTST: Change at Month 12 of exposure	58.15 minutes Interval 49.29 to 67.01	66.50 minutes Interval 57.41 to 75.6	—

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=444 Participants 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.	Lemborexant 5 mg n=437 Participants Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).	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).
Persistence of Effect: Mean Change From Baseline in sSE at Months 3, 6, 9, and 12 Compared to Month 1 Change at Month 1 of exposure	6.35 percentage of sTST Interval 5.13 to 7.57	7.32 percentage of sTST Interval 6.09 to 8.56	—
Persistence of Effect: Mean Change From Baseline in sSE at Months 3, 6, 9, and 12 Compared to Month 1 Change at Month 3 of exposure	10.01 percentage of sTST Interval 8.69 to 11.34	10.25 percentage of sTST Interval 8.9 to 11.6	—
Persistence of Effect: Mean Change From Baseline in sSE at Months 3, 6, 9, and 12 Compared to Month 1 Change at Month 6 of exposure	11.10 percentage of sTST Interval 9.61 to 12.58	11.08 percentage of sTST Interval 9.56 to 12.6	—
Persistence of Effect: Mean Change From Baseline in sSE at Months 3, 6, 9, and 12 Compared to Month 1 Change at Month 9 of exposure	11.85 percentage of sTST Interval 10.13 to 13.56	12.84 percentage of sTST Interval 11.08 to 14.61	—
Persistence of Effect: Mean Change From Baseline in sSE at Months 3, 6, 9, and 12 Compared to Month 1 Change at Month 12 of exposure	12.61 percentage of sTST Interval 10.92 to 14.31	13.66 percentage of sTST Interval 11.92 to 15.4	—

SECONDARY outcome

Timeframe: Baseline, Month 7, 9, 12

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.

Outcome measures

Outcome measures
Measure	Placebo n=444 Participants 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.	Lemborexant 5 mg n=437 Participants Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).	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).
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: Change at Month 7 of exposure	-28.55 minutes Interval -32.39 to -24.7	-29.46 minutes Interval -33.42 to -25.5	—
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 sTST: Change at Month 7 of exposure	75.00 minutes Interval 65.3 to 84.71	76.95 minutes Interval 66.97 to 86.92	—
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 sTST: Change at Month 9 of exposure	78.69 minutes Interval 68.99 to 88.39	81.24 minutes Interval 71.26 to 91.23	—
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: Change at Month 12 of exposure	-31.40 minutes Interval -34.85 to -27.96	-31.33 minutes Interval -34.88 to -27.78	—
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 sWASO: Change at Month 7 of exposure	-45.62 minutes Interval -52.53 to -38.7	-43.09 minutes Interval -50.2 to -35.99	—
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 sWASO: Change at Month 9 of exposure	-47.70 minutes Interval -54.54 to -40.86	-48.87 minutes Interval -55.92 to -41.82	—
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 sWASO: Change at Month 12 of exposure	-48.46 minutes Interval -55.35 to -41.57	-49.28 minutes Interval -56.36 to -42.19	—
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 sTST: Change at Month 12 of exposure	78.61 minutes Interval 68.61 to 88.61	83.61 minutes Interval 73.33 to 93.9	—
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: Change at Month 9 of exposure	-32.10 minutes Interval -35.39 to -28.8	-30.91 minutes Interval -34.31 to -27.52	—

SECONDARY outcome

Timeframe: Baseline, Month 7, 9, 12

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.

Outcome measures

Outcome measures
Measure	Placebo n=444 Participants 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.	Lemborexant 5 mg n=437 Participants Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).	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).
Persistence of Effect: Mean Change From Period 2 Baseline (Month 6) in sSE at Months 9 and 12 Compared to Month 7 Change at Month 9 of exposure	16.54 percentage of sTST Interval 14.88 to 18.2	16.49 percentage of sTST Interval 14.78 to 18.2	—
Persistence of Effect: Mean Change From Period 2 Baseline (Month 6) in sSE at Months 9 and 12 Compared to Month 7 Change at Month 7 of exposure	12.88 percentage of sTST Interval 9.01 to 16.75	15.12 percentage of sTST Interval 11.13 to 19.1	—
Persistence of Effect: Mean Change From Period 2 Baseline (Month 6) in sSE at Months 9 and 12 Compared to Month 7 Change at Month 12 of exposure	16.34 percentage of sTST Interval 14.7 to 17.98	16.82 percentage of sTST Interval 15.13 to 18.5	—

SECONDARY outcome

Timeframe: Baseline, Month 1, 3, 6

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.

Outcome measures

Outcome measures
Measure	Placebo n=444 Participants 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.	Lemborexant 5 mg n=437 Participants Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).	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).
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 sWASO: Change at Month 1 of exposure	-17.26 minutes Interval -22.54 to -11.97	-18.69 minutes Interval -24.05 to -13.33	—
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 sWASO: Change at Month 3 of exposure	-31.34 minutes Interval -37.12 to -25.57	-28.97 minutes Interval -34.86 to -23.09	—
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: Change at Month 1 of exposure	-17.17 minutes Interval -19.76 to -14.58	-18.64 minutes Interval -21.26 to -16.02	—
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: Change at Month 3 of exposure	-21.47 minutes Interval -24.46 to -18.48	-21.58 minutes Interval -24.61 to -18.54	—
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: Change at Month 6 of exposure	-24.13 minutes Interval -27.22 to -21.04	-22.99 minutes Interval -26.14 to -19.83	—
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 sWASO: Change at Month 6 of exposure	-36.10 minutes Interval -42.57 to -29.63	-31.54 minutes Interval -38.16 to -24.91	—
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 sTST: Change at Month 1 of exposure	31.98 minutes Interval 25.54 to 38.42	38.04 minutes Interval 31.51 to 44.57	—
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 sTST: Change at Month 3 of exposure	49.27 minutes Interval 42.33 to 56.22	53.51 minutes Interval 46.42 to 60.61	—
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 sTST: Change at Month 6 of exposure	54.99 minutes Interval 47.18 to 62.8	56.36 minutes Interval 48.35 to 64.36	—

SECONDARY outcome

Timeframe: Baseline, Month 1, 3, 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=444 Participants 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.	Lemborexant 5 mg n=437 Participants Participants received lemborexant 5 mg, tablets, orally, once daily through Month 1-6 (in Period 1) and Month 7-12 (in Period 2).	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).
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 Change at Month 3 of exposure	10.01 percentage of sTST Interval 8.69 to 11.34	10.25 percentage of sTST Interval 8.9 to 11.6	—
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 Change at Month 1 of exposure	6.35 percentage of sTST Interval 5.13 to 7.57	7.32 percentage of sTST Interval 6.09 to 8.56	—
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 Change at Month 6 of exposure	11.10 percentage of sTST Interval 9.61 to 12.58	11.08 percentage of sTST Interval 9.56 to 12.6	—

Adverse Events

Placebo

Serious events: 5 serious events

Other events: 75 other events

Deaths: 0 deaths

Lemborexant 5 mg

Serious events: 18 serious events

Other events: 129 other events

Deaths: 0 deaths

Lemborexant 10 mg

Serious events: 16 serious events

Other events: 140 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=319 participants at risk 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.	Lemborexant 5 mg n=447 participants at risk 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).	Lemborexant 10 mg n=437 participants at risk 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).
Infections and infestations Influenza	4.7% 15/319 • Number of events 15 • From start of study drug administration up to Week 54 Placebo arm included AE data for participants who received placebo in Period 1. Lemborexant 5 mg and 10 mg arms included AE data of participants who received either lemborexant 5 mg or 10 mg throughout the study (Period 1 and 2 both) and participants re-randomized from placebo (in Period 1) to either lemborexant 5 mg or lemborexant 10 mg in Period 2.	4.9% 22/447 • Number of events 22 • From start of study drug administration up to Week 54 Placebo arm included AE data for participants who received placebo in Period 1. Lemborexant 5 mg and 10 mg arms included AE data of participants who received either lemborexant 5 mg or 10 mg throughout the study (Period 1 and 2 both) and participants re-randomized from placebo (in Period 1) to either lemborexant 5 mg or lemborexant 10 mg in Period 2.	5.9% 26/437 • Number of events 29 • From start of study drug administration up to Week 54 Placebo arm included AE data for participants who received placebo in Period 1. Lemborexant 5 mg and 10 mg arms included AE data of participants who received either lemborexant 5 mg or 10 mg throughout the study (Period 1 and 2 both) and participants re-randomized from placebo (in Period 1) to either lemborexant 5 mg or lemborexant 10 mg in Period 2.
Infections and infestations Nasopharyngitis	12.5% 40/319 • Number of events 43 • From start of study drug administration up to Week 54 Placebo arm included AE data for participants who received placebo in Period 1. Lemborexant 5 mg and 10 mg arms included AE data of participants who received either lemborexant 5 mg or 10 mg throughout the study (Period 1 and 2 both) and participants re-randomized from placebo (in Period 1) to either lemborexant 5 mg or lemborexant 10 mg in Period 2.	11.4% 51/447 • Number of events 67 • From start of study drug administration up to Week 54 Placebo arm included AE data for participants who received placebo in Period 1. Lemborexant 5 mg and 10 mg arms included AE data of participants who received either lemborexant 5 mg or 10 mg throughout the study (Period 1 and 2 both) and participants re-randomized from placebo (in Period 1) to either lemborexant 5 mg or lemborexant 10 mg in Period 2.	11.0% 48/437 • Number of events 56 • From start of study drug administration up to Week 54 Placebo arm included AE data for participants who received placebo in Period 1. Lemborexant 5 mg and 10 mg arms included AE data of participants who received either lemborexant 5 mg or 10 mg throughout the study (Period 1 and 2 both) and participants re-randomized from placebo (in Period 1) to either lemborexant 5 mg or lemborexant 10 mg in Period 2.
Nervous system disorders Headache	6.6% 21/319 • Number of events 33 • From start of study drug administration up to Week 54 Placebo arm included AE data for participants who received placebo in Period 1. Lemborexant 5 mg and 10 mg arms included AE data of participants who received either lemborexant 5 mg or 10 mg throughout the study (Period 1 and 2 both) and participants re-randomized from placebo (in Period 1) to either lemborexant 5 mg or lemborexant 10 mg in Period 2.	9.6% 43/447 • Number of events 76 • From start of study drug administration up to Week 54 Placebo arm included AE data for participants who received placebo in Period 1. Lemborexant 5 mg and 10 mg arms included AE data of participants who received either lemborexant 5 mg or 10 mg throughout the study (Period 1 and 2 both) and participants re-randomized from placebo (in Period 1) to either lemborexant 5 mg or lemborexant 10 mg in Period 2.	7.3% 32/437 • Number of events 41 • From start of study drug administration up to Week 54 Placebo arm included AE data for participants who received placebo in Period 1. Lemborexant 5 mg and 10 mg arms included AE data of participants who received either lemborexant 5 mg or 10 mg throughout the study (Period 1 and 2 both) and participants re-randomized from placebo (in Period 1) to either lemborexant 5 mg or lemborexant 10 mg in Period 2.
Nervous system disorders Somnolence	1.6% 5/319 • Number of events 5 • From start of study drug administration up to Week 54 Placebo arm included AE data for participants who received placebo in Period 1. Lemborexant 5 mg and 10 mg arms included AE data of participants who received either lemborexant 5 mg or 10 mg throughout the study (Period 1 and 2 both) and participants re-randomized from placebo (in Period 1) to either lemborexant 5 mg or lemborexant 10 mg in Period 2.	8.5% 38/447 • Number of events 44 • From start of study drug administration up to Week 54 Placebo arm included AE data for participants who received placebo in Period 1. Lemborexant 5 mg and 10 mg arms included AE data of participants who received either lemborexant 5 mg or 10 mg throughout the study (Period 1 and 2 both) and participants re-randomized from placebo (in Period 1) to either lemborexant 5 mg or lemborexant 10 mg in Period 2.	13.7% 60/437 • Number of events 64 • From start of study drug administration up to Week 54 Placebo arm included AE data for participants who received placebo in Period 1. Lemborexant 5 mg and 10 mg arms included AE data of participants who received either lemborexant 5 mg or 10 mg throughout the study (Period 1 and 2 both) and participants re-randomized from placebo (in Period 1) to either lemborexant 5 mg or lemborexant 10 mg in Period 2.

Additional Information

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