Trial Outcomes & Findings for Study of Lemborexant for Irregular Sleep-Wake Rhythm Disorder and Mild to Moderate Alzheimer's Disease Dementia (NCT NCT03001557)

NCT ID: NCT03001557

Last Updated: 2021-05-17

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 63 participants
• Primary outcome timeframe: Baseline, Week 1
• Results posted on: 2021-05-17

Participant Flow

Participants took part in the study at 57 investigative sites in the United States, Japan and United Kingdom from 20 Dec 2016 to 17 Apr 2020.

In Core phase, a total of 214 participants were screened, of which 151 were screen failures and 63 were randomized and enrolled in to the study. Of these 63 participants, 62 received the study treatment (1 participant was inadvertently randomized but did not receive any study drug). In Extension phase, a total of 25 participants who completed the Core Phase, gave consent to join Extension phase were enrolled and treated.

Participant milestones

Measure	Core Phase: Lemborexant-matched Placebo Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg Participants received one lemborexant 2.5 milligrams (mg) and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study end of study (EOS) visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for Irregular Sleep-Wake Rhythm Disorder (ISWRD) is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase STARTED	12	12	14	13	12	0	0	0
Core Phase Treated	12	12	13	13	12	0	0	0
Core Phase COMPLETED	12	12	13	13	12	0	0	0
Core Phase NOT COMPLETED	0	0	1	0	0	0	0	0
Extension Phase STARTED	0	0	0	0	0	5	14	6
Extension Phase COMPLETED	0	0	0	0	0	0	0	0
Extension Phase NOT COMPLETED	0	0	0	0	0	5	14	6

Reasons for withdrawal

Measure	Core Phase: Lemborexant-matched Placebo Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg Participants received one lemborexant 2.5 milligrams (mg) and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study end of study (EOS) visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for Irregular Sleep-Wake Rhythm Disorder (ISWRD) is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase Randomized but not treated	0	0	1	0	0	0	0	0
Extension Phase Adverse Event	0	0	0	0	0	2	0	0
Extension Phase Withdrawal by Subject	0	0	0	0	0	1	5	2
Extension Phase Lost to Follow-up	0	0	0	0	0	0	2	1
Extension Phase Administrative Reason	0	0	0	0	0	1	3	3
Extension Phase Loss of caregiver	0	0	0	0	0	0	1	0
Extension Phase Others	0	0	0	0	0	1	3	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Total n=62 Participants Total of all reporting groups
Age, Continuous	75.3 years STANDARD_DEVIATION 6.15 • n=5 Participants	76.5 years STANDARD_DEVIATION 6.32 • n=7 Participants	76.9 years STANDARD_DEVIATION 7.98 • n=5 Participants	71.8 years STANDARD_DEVIATION 7.05 • n=4 Participants	71.9 years STANDARD_DEVIATION 6.11 • n=21 Participants	74.5 years STANDARD_DEVIATION 6.94 • n=8 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants	6 Participants n=4 Participants	10 Participants n=21 Participants	37 Participants n=8 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	6 Participants n=7 Participants	5 Participants n=5 Participants	7 Participants n=4 Participants	2 Participants n=21 Participants	25 Participants n=8 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	6 Participants n=4 Participants	8 Participants n=21 Participants	24 Participants n=8 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=5 Participants	10 Participants n=7 Participants	9 Participants n=5 Participants	7 Participants n=4 Participants	4 Participants n=21 Participants	38 Participants n=8 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	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	2 Participants n=21 Participants	11 Participants n=8 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	7 Participants n=8 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants	9 Participants n=7 Participants	8 Participants n=5 Participants	9 Participants n=4 Participants	9 Participants n=21 Participants	43 Participants n=8 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=8 Participants

PRIMARY outcome

Timeframe: Baseline, Week 1

Population: The full analysis set (FAS) included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in Mean Actigraphy Sleep Efficiency (aSE) With Lemborexant Compared to Placebo During Week 1 of Treatment Baseline	76.34 percentage of sleep time Standard Deviation 6.559	77.64 percentage of sleep time Standard Deviation 7.883	78.45 percentage of sleep time Standard Deviation 6.844	76.38 percentage of sleep time Standard Deviation 8.037	77.35 percentage of sleep time Standard Deviation 8.624	—	—	—
Core Phase: Change From Baseline in Mean Actigraphy Sleep Efficiency (aSE) With Lemborexant Compared to Placebo During Week 1 of Treatment Change at Week 1	0.14 percentage of sleep time Standard Deviation 5.766	2.43 percentage of sleep time Standard Deviation 3.910	3.87 percentage of sleep time Standard Deviation 4.646	-0.17 percentage of sleep time Standard Deviation 5.861	0.05 percentage of sleep time Standard Deviation 4.475	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 2

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in Mean aSE With Lemborexant Compared to Placebo During Week 2 of Treatment Change at Week 2	-1.31 percentage of sleep time Standard Deviation 7.004	2.17 percentage of sleep time Standard Deviation 2.833	1.65 percentage of sleep time Standard Deviation 4.644	-1.41 percentage of sleep time Standard Deviation 5.896	-0.07 percentage of sleep time Standard Deviation 5.449	—	—	—
Core Phase: Change From Baseline in Mean aSE With Lemborexant Compared to Placebo During Week 2 of Treatment Baseline	76.34 percentage of sleep time Standard Deviation 6.559	77.64 percentage of sleep time Standard Deviation 7.883	78.45 percentage of sleep time Standard Deviation 6.844	76.38 percentage of sleep time Standard Deviation 8.037	77.35 percentage of sleep time Standard Deviation 8.624	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 3

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in Mean aSE With Lemborexant Compared to Placebo During Week 3 of Treatment Baseline	76.34 percentage of sleep time Standard Deviation 6.559	77.64 percentage of sleep time Standard Deviation 7.883	78.45 percentage of sleep time Standard Deviation 6.844	76.38 percentage of sleep time Standard Deviation 8.037	77.35 percentage of sleep time Standard Deviation 8.624	—	—	—
Core Phase: Change From Baseline in Mean aSE With Lemborexant Compared to Placebo During Week 3 of Treatment Change at Week 3	-0.30 percentage of sleep time Standard Deviation 10.552	1.68 percentage of sleep time Standard Deviation 3.229	0.91 percentage of sleep time Standard Deviation 7.571	-1.49 percentage of sleep time Standard Deviation 4.442	1.10 percentage of sleep time Standard Deviation 7.112	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 4

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in Mean aSE With Lemborexant Compared to Placebo During Week 4 of Treatment Baseline	76.34 percentage of sleep time Standard Deviation 6.559	77.64 percentage of sleep time Standard Deviation 7.883	78.45 percentage of sleep time Standard Deviation 6.844	76.38 percentage of sleep time Standard Deviation 8.037	77.35 percentage of sleep time Standard Deviation 8.624	—	—	—
Core Phase: Change From Baseline in Mean aSE With Lemborexant Compared to Placebo During Week 4 of Treatment Change at Week 4	-0.78 percentage of sleep time Standard Deviation 9.555	1.68 percentage of sleep time Standard Deviation 4.696	0.00 percentage of sleep time Standard Deviation 5.547	-1.04 percentage of sleep time Standard Deviation 5.920	-0.81 percentage of sleep time Standard Deviation 7.735	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 1

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in Mean Sleep Fragmentation Index (SFI) During Week 1 of Treatment Baseline	58.51 percentage of immobile bouts Standard Deviation 12.923	53.87 percentage of immobile bouts Standard Deviation 17.594	50.07 percentage of immobile bouts Standard Deviation 12.493	54.75 percentage of immobile bouts Standard Deviation 16.380	54.78 percentage of immobile bouts Standard Deviation 15.338	—	—	—
Core Phase: Change From Baseline in Mean Sleep Fragmentation Index (SFI) During Week 1 of Treatment Change at Week 1	-1.43 percentage of immobile bouts Standard Deviation 9.294	-5.80 percentage of immobile bouts Standard Deviation 11.388	-8.16 percentage of immobile bouts Standard Deviation 8.802	-2.55 percentage of immobile bouts Standard Deviation 11.756	-3.52 percentage of immobile bouts Standard Deviation 8.882	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 2

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in Mean SFI During Week 2 of Treatment Baseline	58.51 percentage of immobile bouts Standard Deviation 12.923	53.87 percentage of immobile bouts Standard Deviation 17.594	50.07 percentage of immobile bouts Standard Deviation 12.493	54.75 percentage of immobile bouts Standard Deviation 16.380	54.78 percentage of immobile bouts Standard Deviation 15.338	—	—	—
Core Phase: Change From Baseline in Mean SFI During Week 2 of Treatment Change at Week 2	2.52 percentage of immobile bouts Standard Deviation 11.845	-6.91 percentage of immobile bouts Standard Deviation 5.994	-4.95 percentage of immobile bouts Standard Deviation 8.399	0.34 percentage of immobile bouts Standard Deviation 14.194	-3.18 percentage of immobile bouts Standard Deviation 8.971	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 3

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in Mean SFI During Week 3 of Treatment Change at Week 3	-3.30 percentage of immobile bouts Standard Deviation 18.512	-2.79 percentage of immobile bouts Standard Deviation 7.541	-5.22 percentage of immobile bouts Standard Deviation 11.974	0.36 percentage of immobile bouts Standard Deviation 9.018	-4.92 percentage of immobile bouts Standard Deviation 9.572	—	—	—
Core Phase: Change From Baseline in Mean SFI During Week 3 of Treatment Baseline	58.51 percentage of immobile bouts Standard Deviation 12.923	53.87 percentage of immobile bouts Standard Deviation 17.594	50.07 percentage of immobile bouts Standard Deviation 12.493	54.75 percentage of immobile bouts Standard Deviation 16.380	54.78 percentage of immobile bouts Standard Deviation 15.338	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 4

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in Mean SFI During Week 4 of Treatment Baseline	58.51 percentage of immobile bouts Standard Deviation 12.923	53.87 percentage of immobile bouts Standard Deviation 17.594	50.07 percentage of immobile bouts Standard Deviation 12.493	54.75 percentage of immobile bouts Standard Deviation 16.380	54.78 percentage of immobile bouts Standard Deviation 15.338	—	—	—
Core Phase: Change From Baseline in Mean SFI During Week 4 of Treatment Change at Week 4	-1.39 percentage of immobile bouts Standard Deviation 19.383	-1.35 percentage of immobile bouts Standard Deviation 8.821	-1.96 percentage of immobile bouts Standard Deviation 8.459	-0.45 percentage of immobile bouts Standard Deviation 13.389	-1.68 percentage of immobile bouts Standard Deviation 12.683	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 1

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in the Mean Duration of Wake Bouts (aMeanDurWB) During Week 1 of Treatment Baseline	20.32 minutes Standard Deviation 6.625	20.40 minutes Standard Deviation 5.140	20.62 minutes Standard Deviation 5.898	21.89 minutes Standard Deviation 4.885	21.94 minutes Standard Deviation 7.790	—	—	—
Core Phase: Change From Baseline in the Mean Duration of Wake Bouts (aMeanDurWB) During Week 1 of Treatment Change at Week 1	-1.65 minutes Standard Deviation 5.078	-1.99 minutes Standard Deviation 2.825	-0.51 minutes Standard Deviation 6.522	-0.82 minutes Standard Deviation 5.722	1.54 minutes Standard Deviation 5.378	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 2

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in the aMeanDurWB During Week 2 of Treatment Baseline	20.32 minutes Standard Deviation 6.625	20.40 minutes Standard Deviation 5.140	20.62 minutes Standard Deviation 5.898	21.89 minutes Standard Deviation 4.885	21.94 minutes Standard Deviation 7.790	—	—	—
Core Phase: Change From Baseline in the aMeanDurWB During Week 2 of Treatment Change at Week 2	-0.32 minutes Standard Deviation 7.904	1.79 minutes Standard Deviation 12.957	4.71 minutes Standard Deviation 13.845	1.54 minutes Standard Deviation 6.333	2.57 minutes Standard Deviation 6.708	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 3

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in the aMeanDurWB During Week 3 of Treatment Baseline	20.32 minutes Standard Deviation 6.625	20.40 minutes Standard Deviation 5.140	20.62 minutes Standard Deviation 5.898	21.89 minutes Standard Deviation 4.885	21.94 minutes Standard Deviation 7.790	—	—	—
Core Phase: Change From Baseline in the aMeanDurWB During Week 3 of Treatment Change at Week 3	-2.88 minutes Standard Deviation 7.928	3.67 minutes Standard Deviation 7.833	-0.52 minutes Standard Deviation 4.595	-0.64 minutes Standard Deviation 5.482	2.76 minutes Standard Deviation 7.489	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 4

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in the aMeanDurWB During Week 4 of Treatment Baseline	20.32 minutes Standard Deviation 6.625	20.40 minutes Standard Deviation 5.140	20.62 minutes Standard Deviation 5.898	21.89 minutes Standard Deviation 4.885	21.94 minutes Standard Deviation 7.790	—	—	—
Core Phase: Change From Baseline in the aMeanDurWB During Week 4 of Treatment Change at Week 4	-1.26 minutes Standard Deviation 8.621	-0.43 minutes Standard Deviation 8.053	3.16 minutes Standard Deviation 8.140	-2.03 minutes Standard Deviation 4.947	3.38 minutes Standard Deviation 12.354	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 1

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in Mean Actigraphy Wake Efficiency (aWE) During Week 1 of Treatment Baseline	69.74 percentage of wake time Standard Deviation 12.609	70.57 percentage of wake time Standard Deviation 11.669	72.53 percentage of wake time Standard Deviation 11.473	67.19 percentage of wake time Standard Deviation 11.523	70.67 percentage of wake time Standard Deviation 11.221	—	—	—
Core Phase: Change From Baseline in Mean Actigraphy Wake Efficiency (aWE) During Week 1 of Treatment Change at Week 1	0.59 percentage of wake time Standard Deviation 4.177	-2.41 percentage of wake time Standard Deviation 6.726	1.09 percentage of wake time Standard Deviation 6.793	-1.55 percentage of wake time Standard Deviation 9.216	-2.37 percentage of wake time Standard Deviation 8.779	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 2

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in Mean aWE During Week 2 of Treatment Baseline	69.74 percentage of wake time Standard Deviation 12.609	70.57 percentage of wake time Standard Deviation 11.669	72.53 percentage of wake time Standard Deviation 11.473	67.19 percentage of wake time Standard Deviation 11.523	70.67 percentage of wake time Standard Deviation 11.221	—	—	—
Core Phase: Change From Baseline in Mean aWE During Week 2 of Treatment Change at Week 2	2.14 percentage of wake time Standard Deviation 2.773	-1.54 percentage of wake time Standard Deviation 6.550	1.04 percentage of wake time Standard Deviation 7.511	-3.16 percentage of wake time Standard Deviation 12.816	-0.63 percentage of wake time Standard Deviation 5.617	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 3

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in Mean aWE During Week 3 of Treatment Baseline	69.74 percentage of wake time Standard Deviation 12.609	70.57 percentage of wake time Standard Deviation 11.669	72.53 percentage of wake time Standard Deviation 11.473	67.19 percentage of wake time Standard Deviation 11.523	70.67 percentage of wake time Standard Deviation 11.221	—	—	—
Core Phase: Change From Baseline in Mean aWE During Week 3 of Treatment Change at Week 3	1.64 percentage of wake time Standard Deviation 5.451	-2.37 percentage of wake time Standard Deviation 6.239	2.34 percentage of wake time Standard Deviation 8.370	-4.99 percentage of wake time Standard Deviation 11.479	-1.83 percentage of wake time Standard Deviation 5.579	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 4

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in Mean aWE During Week 4 of Treatment Change at Week 4	2.03 percentage of wake time Standard Deviation 6.841	-2.29 percentage of wake time Standard Deviation 7.724	3.62 percentage of wake time Standard Deviation 8.586	-2.65 percentage of wake time Standard Deviation 9.627	-0.43 percentage of wake time Standard Deviation 5.848	—	—	—
Core Phase: Change From Baseline in Mean aWE During Week 4 of Treatment Baseline	69.74 percentage of wake time Standard Deviation 12.609	70.57 percentage of wake time Standard Deviation 11.669	72.53 percentage of wake time Standard Deviation 11.473	67.19 percentage of wake time Standard Deviation 11.523	70.67 percentage of wake time Standard Deviation 11.221	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 1

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in Mean Wake Fragmentation Index (WFI) During Week 1 of Treatment Baseline	92.43 percentage of immobile bouts Standard Deviation 18.547	85.72 percentage of immobile bouts Standard Deviation 16.137	86.53 percentage of immobile bouts Standard Deviation 18.705	94.76 percentage of immobile bouts Standard Deviation 17.262	87.96 percentage of immobile bouts Standard Deviation 15.928	—	—	—
Core Phase: Change From Baseline in Mean Wake Fragmentation Index (WFI) During Week 1 of Treatment Change at Week 1	-0.14 percentage of immobile bouts Standard Deviation 6.968	4.22 percentage of immobile bouts Standard Deviation 9.988	-2.18 percentage of immobile bouts Standard Deviation 10.571	2.01 percentage of immobile bouts Standard Deviation 13.017	3.25 percentage of immobile bouts Standard Deviation 13.006	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 2

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in Mean WFI During Week 2 of Treatment Baseline	92.43 percentage of immobile bouts Standard Deviation 18.547	85.72 percentage of immobile bouts Standard Deviation 16.137	86.53 percentage of immobile bouts Standard Deviation 18.705	94.76 percentage of immobile bouts Standard Deviation 17.262	87.96 percentage of immobile bouts Standard Deviation 15.928	—	—	—
Core Phase: Change From Baseline in Mean WFI During Week 2 of Treatment Change at Week 2	-3.76 percentage of immobile bouts Standard Deviation 3.940	4.12 percentage of immobile bouts Standard Deviation 8.671	-2.36 percentage of immobile bouts Standard Deviation 11.453	5.09 percentage of immobile bouts Standard Deviation 19.006	1.78 percentage of immobile bouts Standard Deviation 9.271	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 3

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in Mean WFI During Week 3 of Treatment Baseline	92.43 percentage of immobile bouts Standard Deviation 18.547	85.72 percentage of immobile bouts Standard Deviation 16.137	86.53 percentage of immobile bouts Standard Deviation 18.705	94.76 percentage of immobile bouts Standard Deviation 17.262	87.96 percentage of immobile bouts Standard Deviation 15.928	—	—	—
Core Phase: Change From Baseline in Mean WFI During Week 3 of Treatment Change at Week 3	-1.65 percentage of immobile bouts Standard Deviation 7.980	4.70 percentage of immobile bouts Standard Deviation 9.674	-3.69 percentage of immobile bouts Standard Deviation 13.236	6.88 percentage of immobile bouts Standard Deviation 16.704	2.10 percentage of immobile bouts Standard Deviation 8.631	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 4

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in Mean WFI During Week 4 of Treatment Change at Week 4	-3.01 percentage of immobile bouts Standard Deviation 10.620	4.55 percentage of immobile bouts Standard Deviation 10.930	-6.93 percentage of immobile bouts Standard Deviation 14.428	2.77 percentage of immobile bouts Standard Deviation 13.407	1.22 percentage of immobile bouts Standard Deviation 8.054	—	—	—
Core Phase: Change From Baseline in Mean WFI During Week 4 of Treatment Baseline	92.43 percentage of immobile bouts Standard Deviation 18.547	85.72 percentage of immobile bouts Standard Deviation 16.137	86.53 percentage of immobile bouts Standard Deviation 18.705	94.76 percentage of immobile bouts Standard Deviation 17.262	87.96 percentage of immobile bouts Standard Deviation 15.928	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 1

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in the Mean Duration of Sleep Bouts (aMeanDurSB) During Week 1 of Treatment Baseline	18.36 minutes Standard Deviation 4.620	20.65 minutes Standard Deviation 3.638	23.13 minutes Standard Deviation 5.919	19.84 minutes Standard Deviation 3.364	23.30 minutes Standard Deviation 10.862	—	—	—
Core Phase: Change From Baseline in the Mean Duration of Sleep Bouts (aMeanDurSB) During Week 1 of Treatment Change at Week 1	2.15 minutes Standard Deviation 2.539	0.09 minutes Standard Deviation 4.056	-1.12 minutes Standard Deviation 5.202	-0.40 minutes Standard Deviation 3.394	-3.19 minutes Standard Deviation 10.405	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 2

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in the aMeanDurSB During Week 2 of Treatment Baseline	18.36 minutes Standard Deviation 4.620	20.65 minutes Standard Deviation 3.638	23.13 minutes Standard Deviation 5.919	19.84 minutes Standard Deviation 3.364	23.30 minutes Standard Deviation 10.862	—	—	—
Core Phase: Change From Baseline in the aMeanDurSB During Week 2 of Treatment Change at Week 2	0.25 minutes Standard Deviation 2.999	-0.88 minutes Standard Deviation 4.679	-2.52 minutes Standard Deviation 5.965	-0.80 minutes Standard Deviation 2.961	-3.95 minutes Standard Deviation 8.980	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 3

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in the aMeanDurSB During Week 3 of Treatment Baseline	18.36 minutes Standard Deviation 4.620	20.65 minutes Standard Deviation 3.638	23.13 minutes Standard Deviation 5.919	19.84 minutes Standard Deviation 3.364	23.30 minutes Standard Deviation 10.862	—	—	—
Core Phase: Change From Baseline in the aMeanDurSB During Week 3 of Treatment Change at Week 3	-0.14 minutes Standard Deviation 3.249	-1.17 minutes Standard Deviation 4.056	-3.80 minutes Standard Deviation 3.701	-0.68 minutes Standard Deviation 2.292	-4.15 minutes Standard Deviation 10.264	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 4

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in the aMeanDurSB During Week 4 of Treatment Baseline	18.36 minutes Standard Deviation 4.620	20.65 minutes Standard Deviation 3.638	23.13 minutes Standard Deviation 5.919	19.84 minutes Standard Deviation 3.364	23.30 minutes Standard Deviation 10.862	—	—	—
Core Phase: Change From Baseline in the aMeanDurSB During Week 4 of Treatment Change at Week 4	1.00 minutes Standard Deviation 4.568	-1.31 minutes Standard Deviation 3.639	-2.80 minutes Standard Deviation 5.727	-0.03 minutes Standard Deviation 2.307	-5.30 minutes Standard Deviation 9.745	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 1

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in Mean Intradaily Variability Over Week 1 of Treatment Baseline	1.10 ratio Standard Deviation 0.262	0.90 ratio Standard Deviation 0.272	0.98 ratio Standard Deviation 0.295	1.10 ratio Standard Deviation 0.295	1.03 ratio Standard Deviation 0.330	—	—	—
Core Phase: Change From Baseline in Mean Intradaily Variability Over Week 1 of Treatment Change at Week 1	-0.01 ratio Standard Deviation 0.200	0.06 ratio Standard Deviation 0.218	-0.03 ratio Standard Deviation 0.237	0.10 ratio Standard Deviation 0.271	-0.01 ratio Standard Deviation 0.278	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 2

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in Mean Intradaily Variability Over Week 2 of Treatment Baseline	1.10 ratio Standard Deviation 0.262	0.90 ratio Standard Deviation 0.272	0.98 ratio Standard Deviation 0.295	1.10 ratio Standard Deviation 0.295	1.03 ratio Standard Deviation 0.330	—	—	—
Core Phase: Change From Baseline in Mean Intradaily Variability Over Week 2 of Treatment Change at Week 2	-0.05 ratio Standard Deviation 0.132	0.14 ratio Standard Deviation 0.325	0.02 ratio Standard Deviation 0.235	0.07 ratio Standard Deviation 0.143	0.05 ratio Standard Deviation 0.234	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 3

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in Mean Intradaily Variability Over Week 3 of Treatment Baseline	1.10 ratio Standard Deviation 0.262	0.90 ratio Standard Deviation 0.272	0.98 ratio Standard Deviation 0.295	1.10 ratio Standard Deviation 0.295	1.03 ratio Standard Deviation 0.330	—	—	—
Core Phase: Change From Baseline in Mean Intradaily Variability Over Week 3 of Treatment Change at Week 3	-0.06 ratio Standard Deviation 0.243	0.07 ratio Standard Deviation 0.246	-0.00 ratio Standard Deviation 0.241	-0.06 ratio Standard Deviation 0.311	-0.01 ratio Standard Deviation 0.219	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 4

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in Mean Intradaily Variability Over Week 4 of Treatment Baseline	1.10 ratio Standard Deviation 0.262	0.90 ratio Standard Deviation 0.272	0.98 ratio Standard Deviation 0.295	1.10 ratio Standard Deviation 0.295	1.03 ratio Standard Deviation 0.330	—	—	—
Core Phase: Change From Baseline in Mean Intradaily Variability Over Week 4 of Treatment Change at Week 4	-0.10 ratio Standard Deviation 0.324	0.10 ratio Standard Deviation 0.196	0.02 ratio Standard Deviation 0.157	-0.12 ratio Standard Deviation 0.274	-0.10 ratio Standard Deviation 0.222	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 1

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in Mean Interdaily Stability (IS) Over Week 1 of Treatment Baseline	0.45 ratio Standard Deviation 0.173	0.47 ratio Standard Deviation 0.111	0.49 ratio Standard Deviation 0.118	0.46 ratio Standard Deviation 0.160	0.41 ratio Standard Deviation 0.104	—	—	—
Core Phase: Change From Baseline in Mean Interdaily Stability (IS) Over Week 1 of Treatment Change at Week 1	0.04 ratio Standard Deviation 0.083	-0.02 ratio Standard Deviation 0.089	0.04 ratio Standard Deviation 0.115	-0.00 ratio Standard Deviation 0.155	0.06 ratio Standard Deviation 0.063	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 2

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in Mean IS Over Week 2 of Treatment Baseline	0.45 ratio Standard Deviation 0.173	0.47 ratio Standard Deviation 0.111	0.49 ratio Standard Deviation 0.118	0.46 ratio Standard Deviation 0.160	0.41 ratio Standard Deviation 0.104	—	—	—
Core Phase: Change From Baseline in Mean IS Over Week 2 of Treatment Change at Week 2	0.06 ratio Standard Deviation 0.093	-0.01 ratio Standard Deviation 0.101	0.03 ratio Standard Deviation 0.133	-0.06 ratio Standard Deviation 0.091	0.09 ratio Standard Deviation 0.085	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 3

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in Mean IS Over Week 3 of Treatment Baseline	0.45 ratio Standard Deviation 0.173	0.47 ratio Standard Deviation 0.111	0.49 ratio Standard Deviation 0.118	0.46 ratio Standard Deviation 0.160	0.41 ratio Standard Deviation 0.104	—	—	—
Core Phase: Change From Baseline in Mean IS Over Week 3 of Treatment Change at Week 3	0.03 ratio Standard Deviation 0.104	-0.01 ratio Standard Deviation 0.107	0.03 ratio Standard Deviation 0.115	-0.04 ratio Standard Deviation 0.136	0.04 ratio Standard Deviation 0.075	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 4

Population: FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in Mean IS Over Week 4 of Treatment Baseline	0.45 ratio Standard Deviation 0.173	0.47 ratio Standard Deviation 0.111	0.49 ratio Standard Deviation 0.118	0.46 ratio Standard Deviation 0.160	0.41 ratio Standard Deviation 0.104	—	—	—
Core Phase: Change From Baseline in Mean IS Over Week 4 of Treatment Change at Week 4	0.02 ratio Standard Deviation 0.098	0.01 ratio Standard Deviation 0.119	0.08 ratio Standard Deviation 0.092	0.03 ratio Standard Deviation 0.127	0.00 ratio Standard Deviation 0.102	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 1

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in Average Activity Counts Across Least Active 5-hour Period (L5) Per 24-Hour Period Over Week 1 of Treatment Baseline	1163.5 activity count Standard Deviation 373.3	1266.4 activity count Standard Deviation 678.1	1163.2 activity count Standard Deviation 591.8	1257.1 activity count Standard Deviation 836.6	1490.4 activity count Standard Deviation 963.1	—	—	—
Core Phase: Change From Baseline in Average Activity Counts Across Least Active 5-hour Period (L5) Per 24-Hour Period Over Week 1 of Treatment Change at Week 1	200.9 activity count Standard Deviation 633.3	-259.8 activity count Standard Deviation 450.3	-243.2 activity count Standard Deviation 333.6	-211.6 activity count Standard Deviation 378.3	-434.2 activity count Standard Deviation 509.1	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 2

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in Average Activity Counts Across L5 Per 24-Hour Period Over Week 2 of Treatment Baseline	1163.5 activity count Standard Deviation 373.3	1266.4 activity count Standard Deviation 678.1	1163.2 activity count Standard Deviation 591.8	1257.1 activity count Standard Deviation 836.6	1490.4 activity count Standard Deviation 963.1	—	—	—
Core Phase: Change From Baseline in Average Activity Counts Across L5 Per 24-Hour Period Over Week 2 of Treatment Change at Week 2	85.8 activity count Standard Deviation 525.3	-259.8 activity count Standard Deviation 244.9	-218.7 activity count Standard Deviation 321.6	218.5 activity count Standard Deviation 455.9	-246.1 activity count Standard Deviation 637.6	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 3

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in Average Activity Counts Across L5 Per 24-Hour Period Over Week 3 of Treatment Baseline	1163.5 activity count Standard Deviation 373.3	1266.4 activity count Standard Deviation 678.1	1163.2 activity count Standard Deviation 591.8	1257.1 activity count Standard Deviation 836.6	1490.4 activity count Standard Deviation 963.1	—	—	—
Core Phase: Change From Baseline in Average Activity Counts Across L5 Per 24-Hour Period Over Week 3 of Treatment Change at Week 3	299.2 activity count Standard Deviation 1070.2	-265.3 activity count Standard Deviation 507.0	-233.0 activity count Standard Deviation 369.3	-114.6 activity count Standard Deviation 376.6	-396.1 activity count Standard Deviation 543.9	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 4

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in Average Activity Counts Across L5 Per 24-Hour Period Over Week 4 of Treatment Baseline	1163.5 activity count Standard Deviation 373.3	1266.4 activity count Standard Deviation 678.1	1163.2 activity count Standard Deviation 591.8	1257.1 activity count Standard Deviation 836.6	1490.4 activity count Standard Deviation 963.1	—	—	—
Core Phase: Change From Baseline in Average Activity Counts Across L5 Per 24-Hour Period Over Week 4 of Treatment Change at Week 4	293.1 activity count Standard Deviation 662.6	-334.0 activity count Standard Deviation 476.4	-344.5 activity count Standard Deviation 419.1	30.5 activity count Standard Deviation 772.5	-160.7 activity count Standard Deviation 471.3	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 1

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in the Average Activity Count During the Most Active 10-hour Period (M10) Per 24-Hour Period Over Week 1 of Treatment Baseline	8560.4 activity count Standard Deviation 2631.2	11567.0 activity count Standard Deviation 4266.3	12158.1 activity count Standard Deviation 3639.9	10662.1 activity count Standard Deviation 5023.6	11460.5 activity count Standard Deviation 4954.3	—	—	—
Core Phase: Change From Baseline in the Average Activity Count During the Most Active 10-hour Period (M10) Per 24-Hour Period Over Week 1 of Treatment Change at Week 1	59.7 activity count Standard Deviation 1832.6	-731.4 activity count Standard Deviation 3373.5	42.5 activity count Standard Deviation 1789.3	-334.6 activity count Standard Deviation 2659.2	-111.2 activity count Standard Deviation 2558.0	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 2

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in the Average Activity Count During the M10 Per 24-Hour Period Over Week 2 of Treatment Baseline	8560.4 activity count Standard Deviation 2631.2	11567.0 activity count Standard Deviation 4266.3	12158.1 activity count Standard Deviation 3639.9	10662.1 activity count Standard Deviation 5023.6	11460.5 activity count Standard Deviation 4954.3	—	—	—
Core Phase: Change From Baseline in the Average Activity Count During the M10 Per 24-Hour Period Over Week 2 of Treatment Change at Week 2	232.7 activity count Standard Deviation 1829.1	-968.8 activity count Standard Deviation 2885.6	-121.1 activity count Standard Deviation 2137.3	-564.2 activity count Standard Deviation 1975.7	-325.4 activity count Standard Deviation 1585.4	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 3

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in the Average Activity Count During the M10 Per 24-Hour Period Over Week 3 of Treatment Baseline	8560.4 activity count Standard Deviation 2631.2	11567.0 activity count Standard Deviation 4266.3	12158.1 activity count Standard Deviation 3639.9	10662.1 activity count Standard Deviation 5023.6	11460.5 activity count Standard Deviation 4954.3	—	—	—
Core Phase: Change From Baseline in the Average Activity Count During the M10 Per 24-Hour Period Over Week 3 of Treatment Change at Week 3	300.3 activity count Standard Deviation 2094.9	-986.2 activity count Standard Deviation 3502.0	572.6 activity count Standard Deviation 2216.0	-828.3 activity count Standard Deviation 1970.2	-635.8 activity count Standard Deviation 2413.6	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 4

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in the Average Activity Count During the M10 Per 24-Hour Period Over Week 4 of Treatment Baseline	8560.4 activity count Standard Deviation 2631.2	11567.0 activity count Standard Deviation 4266.3	12158.1 activity count Standard Deviation 3639.9	10662.1 activity count Standard Deviation 5023.6	11460.5 activity count Standard Deviation 4954.3	—	—	—
Core Phase: Change From Baseline in the Average Activity Count During the M10 Per 24-Hour Period Over Week 4 of Treatment Change at Week 4	1650.4 activity count Standard Deviation 1815.3	-1392.1 activity count Standard Deviation 2249.3	-477.4 activity count Standard Deviation 963.2	279.8 activity count Standard Deviation 2204.0	-457.8 activity count Standard Deviation 1788.7	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 1

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in Amplitude of the Rest-activity Rhythm (AMP) Over Week 1 of Treatment Baseline	7396.9 activity count Standard Deviation 2728.3	10300.6 activity count Standard Deviation 4235.8	10994.8 activity count Standard Deviation 3601.8	9405.0 activity count Standard Deviation 5133.9	9970.0 activity count Standard Deviation 4905.8	—	—	—
Core Phase: Change From Baseline in Amplitude of the Rest-activity Rhythm (AMP) Over Week 1 of Treatment Change at Week 1	-141.1 activity count Standard Deviation 1583.8	-471.6 activity count Standard Deviation 3414.4	285.8 activity count Standard Deviation 1788.6	-123.0 activity count Standard Deviation 2784.1	323.0 activity count Standard Deviation 2436.0	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 2

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in AMP Over Week 2 of Treatment Baseline	7396.9 activity count Standard Deviation 2728.3	10300.6 activity count Standard Deviation 4235.8	10994.8 activity count Standard Deviation 3601.8	9405.0 activity count Standard Deviation 5133.9	9970.0 activity count Standard Deviation 4905.8	—	—	—
Core Phase: Change From Baseline in AMP Over Week 2 of Treatment Change at Week 2	146.8 activity count Standard Deviation 1603.7	-708.9 activity count Standard Deviation 2934.6	97.6 activity count Standard Deviation 2105.2	-782.7 activity count Standard Deviation 2141.4	-79.3 activity count Standard Deviation 1672.5	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 3

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in AMP Over Week 3 of Treatment Baseline	7396.9 activity count Standard Deviation 2728.3	10300.6 activity count Standard Deviation 4235.8	10994.8 activity count Standard Deviation 3601.8	9405.0 activity count Standard Deviation 5133.9	9970.0 activity count Standard Deviation 4905.8	—	—	—
Core Phase: Change From Baseline in AMP Over Week 3 of Treatment Change at Week 3	1.1 activity count Standard Deviation 1862.7	-721.0 activity count Standard Deviation 3502.2	805.6 activity count Standard Deviation 2195.6	-713.7 activity count Standard Deviation 2178.3	-239.7 activity count Standard Deviation 2592.5	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 4

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in AMP Over Week 4 of Treatment Baseline	7396.9 activity count Standard Deviation 2728.3	10300.6 activity count Standard Deviation 4235.8	10994.8 activity count Standard Deviation 3601.8	9405.0 activity count Standard Deviation 5133.9	9970.0 activity count Standard Deviation 4905.8	—	—	—
Core Phase: Change From Baseline in AMP Over Week 4 of Treatment Change at Week 4	1357.3 activity count Standard Deviation 1801.9	-1058.0 activity count Standard Deviation 2170.9	-132.9 activity count Standard Deviation 840.7	249.4 activity count Standard Deviation 2694.7	-297.1 activity count Standard Deviation 1608.2	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 1

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in Relative Amplitude in the Rest-activity Rhythm (RA) Over Week 1 of Treatment Baseline	0.73 ratio Standard Deviation 0.136	0.79 ratio Standard Deviation 0.141	0.82 ratio Standard Deviation 0.089	0.77 ratio Standard Deviation 0.165	0.76 ratio Standard Deviation 0.148	—	—	—
Core Phase: Change From Baseline in Relative Amplitude in the Rest-activity Rhythm (RA) Over Week 1 of Treatment Change at Week 1	-0.02 ratio Standard Deviation 0.101	0.01 ratio Standard Deviation 0.080	0.03 ratio Standard Deviation 0.067	0.02 ratio Standard Deviation 0.096	0.07 ratio Standard Deviation 0.073	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 2

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in RA Over Week 2 of Treatment Baseline	0.73 ratio Standard Deviation 0.136	0.79 ratio Standard Deviation 0.141	0.82 ratio Standard Deviation 0.089	0.77 ratio Standard Deviation 0.165	0.76 ratio Standard Deviation 0.148	—	—	—
Core Phase: Change From Baseline in RA Over Week 2 of Treatment Change at Week 2	-0.00 ratio Standard Deviation 0.073	0.01 ratio Standard Deviation 0.063	0.03 ratio Standard Deviation 0.052	-0.05 ratio Standard Deviation 0.112	0.05 ratio Standard Deviation 0.091	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 3

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in RA Over Week 3 of Treatment Baseline	0.73 ratio Standard Deviation 0.136	0.79 ratio Standard Deviation 0.141	0.82 ratio Standard Deviation 0.089	0.77 ratio Standard Deviation 0.165	0.76 ratio Standard Deviation 0.148	—	—	—
Core Phase: Change From Baseline in RA Over Week 3 of Treatment Change at Week 3	-0.01 ratio Standard Deviation 0.143	0.01 ratio Standard Deviation 0.088	0.04 ratio Standard Deviation 0.063	0.01 ratio Standard Deviation 0.090	0.06 ratio Standard Deviation 0.080	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 4

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in RA Over Week 4 of Treatment Baseline	0.73 ratio Standard Deviation 0.136	0.79 ratio Standard Deviation 0.141	0.82 ratio Standard Deviation 0.089	0.77 ratio Standard Deviation 0.165	0.76 ratio Standard Deviation 0.148	—	—	—
Core Phase: Change From Baseline in RA Over Week 4 of Treatment Change at Week 4	-0.00 ratio Standard Deviation 0.117	0.01 ratio Standard Deviation 0.060	0.05 ratio Standard Deviation 0.049	0.01 ratio Standard Deviation 0.136	0.02 ratio Standard Deviation 0.069	—	—	—

OTHER_PRE_SPECIFIED outcome

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

Population: The safety analysis set included the group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose safety assessment.

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg n=5 Participants Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg n=14 Participants Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg n=6 Participants Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) TEAEs	4 Participants	3 Participants	3 Participants	4 Participants	6 Participants	4 Participants	10 Participants	5 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) SAEs	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	2 Participants	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 29

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Number of Participants in Each Category With Clinician's Global Impression of Change-Irregular Sleep-Wake Rhythm Disorder (CGIC-ISWRD) Global Score at Day 29 Global score : Marked worsening	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—
Core Phase: Number of Participants in Each Category With Clinician's Global Impression of Change-Irregular Sleep-Wake Rhythm Disorder (CGIC-ISWRD) Global Score at Day 29 Global score: Marked improvement	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—
Core Phase: Number of Participants in Each Category With Clinician's Global Impression of Change-Irregular Sleep-Wake Rhythm Disorder (CGIC-ISWRD) Global Score at Day 29 Global score: Moderate improvement	1 Participants	0 Participants	2 Participants	1 Participants	0 Participants	—	—	—
Core Phase: Number of Participants in Each Category With Clinician's Global Impression of Change-Irregular Sleep-Wake Rhythm Disorder (CGIC-ISWRD) Global Score at Day 29 Global score: Minimal improvement	4 Participants	4 Participants	4 Participants	5 Participants	3 Participants	—	—	—
Core Phase: Number of Participants in Each Category With Clinician's Global Impression of Change-Irregular Sleep-Wake Rhythm Disorder (CGIC-ISWRD) Global Score at Day 29 Global score: No change	6 Participants	5 Participants	4 Participants	3 Participants	7 Participants	—	—	—
Core Phase: Number of Participants in Each Category With Clinician's Global Impression of Change-Irregular Sleep-Wake Rhythm Disorder (CGIC-ISWRD) Global Score at Day 29 Global score: Minimal worsening	0 Participants	3 Participants	2 Participants	3 Participants	1 Participants	—	—	—
Core Phase: Number of Participants in Each Category With Clinician's Global Impression of Change-Irregular Sleep-Wake Rhythm Disorder (CGIC-ISWRD) Global Score at Day 29 Global score : Moderate worsening	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Day 29

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in the Neuropsychiatric Inventory (NPI-10) Total Score at Day 29 Baseline	3.8 score on a scale Standard Deviation 4.13	13.1 score on a scale Standard Deviation 17.77	7.7 score on a scale Standard Deviation 12.32	6.4 score on a scale Standard Deviation 10.27	5.5 score on a scale Standard Deviation 5.73	—	—	—
Core Phase: Change From Baseline in the Neuropsychiatric Inventory (NPI-10) Total Score at Day 29 Change at Day 29	-2.8 score on a scale Standard Deviation 3.64	-3.4 score on a scale Standard Deviation 9.23	-0.3 score on a scale Standard Deviation 5.85	-3.4 score on a scale Standard Deviation 8.95	3.8 score on a scale Standard Deviation 13.02	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Day 29

Population: The FAS included group of randomized participants who received at least 1 dose of randomized study drug and had at least 1 postdose efficacy measurement. Participants who were evaluable for this measure at given time point were included for the assessment.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=12 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 Participants Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=11 Participants Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Core Phase: Change From Baseline in the Sleep Disorders Inventory (SDI) Score at Day 29 Baseline	0.79 score on a scale Standard Deviation 0.692	1.24 score on a scale Standard Deviation 1.576	0.74 score on a scale Standard Deviation 0.653	0.66 score on a scale Standard Deviation 0.748	1.44 score on a scale Standard Deviation 1.708	—	—	—
Core Phase: Change From Baseline in the Sleep Disorders Inventory (SDI) Score at Day 29 Change at Day 29	-0.48 score on a scale Standard Deviation 1.078	-0.10 score on a scale Standard Deviation 0.616	-0.33 score on a scale Standard Deviation 0.503	-0.09 score on a scale Standard Deviation 0.574	-0.49 score on a scale Standard Deviation 1.220	—	—	—

OTHER_PRE_SPECIFIED outcome

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

Population: The safety analysis set included the group of extension phase participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment in extension phase. Here overall number analyzed "N" are the participants who were evaluable for the outcome measure. Number analyzed "n" are the participants who were evaluable for the outcome measure for given categories.

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

Outcome measures

Measure	Core Phase: Lemborexant-matched Placebo n=5 Participants Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 Participants Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=6 Participants Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Extension Phase: Change From Baseline in SDI Total Score. Baseline	1.36 score on a scale Standard Deviation 1.948	0.74 score on a scale Standard Deviation 0.728	1.45 score on a scale Standard Deviation 2.331	—	—	—	—	—
Extension Phase: Change From Baseline in SDI Total Score. Change at Day 133 (Visit 9)	1.40 score on a scale	-0.45 score on a scale Standard Deviation 0.600	-0.63 score on a scale Standard Deviation 0.473	—	—	—	—	—
Extension Phase: Change From Baseline in SDI Total Score. Change at Day 223 (Visit 12)	—	-0.60 score on a scale Standard Deviation 0.693	0.17 score on a scale Standard Deviation 0.306	—	—	—	—	—
Extension Phase: Change From Baseline in SDI Total Score. Change at Day 313 (Visit 15)	—	-0.65 score on a scale Standard Deviation 0.574	-0.17 score on a scale Standard Deviation 1.266	—	—	—	—	—
Extension Phase: Change From Baseline in SDI Total Score. Change at Day 343 (Visit 16)	0.60 score on a scale	0.55 score on a scale Standard Deviation 1.061	0.45 score on a scale Standard Deviation 0.919	—	—	—	—	—
Extension Phase: Change From Baseline in SDI Total Score. Change at Day 373 (Visit 17)	—	-0.20 score on a scale	—	—	—	—	—	—
Extension Phase: Change From Baseline in SDI Total Score. Change at Day 403 (Visit 18)	—	-0.50 score on a scale Standard Deviation 0.539	-0.55 score on a scale Standard Deviation 0.656	—	—	—	—	—
Extension Phase: Change From Baseline in SDI Total Score. Change at Day 493 (Visit 19)	—	-0.13 score on a scale Standard Deviation 0.115	-0.10 score on a scale	—	—	—	—	—
Extension Phase: Change From Baseline in SDI Total Score. Change at Day 583 (Visit 20)	—	-0.15 score on a scale Standard Deviation 0.071	-0.35 score on a scale Standard Deviation 0.354	—	—	—	—	—
Extension Phase: Change From Baseline in SDI Total Score. Change at Day 673 (Visit 21)	—	-0.30 score on a scale	-0.15 score on a scale Standard Deviation 0.071	—	—	—	—	—
Extension Phase: Change From Baseline in SDI Total Score. Change at Day 763 (Visit 22)	—	-0.05 score on a scale Standard Deviation 0.354	—	—	—	—	—	—

Adverse Events

Core Phase: Lemborexant-matched Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Core Phase: Lemborexant 2.5 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Core Phase: Lemborexant 5 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Core Phase: Lemborexant 10 mg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Core Phase: Lemborexant 15 mg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Extension Phase: Lemborexant 5 mg

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Extension Phase: Lemborexant 10 mg

Serious events: 2 serious events

Other events: 10 other events

Deaths: 0 deaths

Extension Phase: Lemborexant 15 mg

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Measure	Core Phase: Lemborexant-matched Placebo n=12 participants at risk Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 participants at risk Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 participants at risk Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 participants at risk Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 participants at risk Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg n=5 participants at risk Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg n=14 participants at risk Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg n=6 participants at risk Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
General disorders Asthenia	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	7.1% 1/14 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Injury, poisoning and procedural complications Ilium fracture	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/14 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	16.7% 1/6 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Nervous system disorders Ischaemic stroke	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	20.0% 1/5 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/14 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Respiratory, thoracic and mediastinal disorders Hypercapnia	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	7.1% 1/14 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	7.1% 1/14 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Vascular disorders Orthostatic hypotension	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	7.1% 1/14 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)

Other adverse events

Measure	Core Phase: Lemborexant-matched Placebo n=12 participants at risk Participants received two lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 2.5 mg n=12 participants at risk Participants received one lemborexant 2.5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 5 mg n=13 participants at risk Participants received one lemborexant 5 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 10 mg n=13 participants at risk Participants received one lemborexant 10 mg and one lemborexant-matched placebo, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Core Phase: Lemborexant 15 mg n=12 participants at risk Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night for 28 consecutive nights in 4-week treatment period.	Extension Phase: Lemborexant 5 mg n=5 participants at risk Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 10 mg n=14 participants at risk Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 10 mg, tablet, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.	Extension Phase: Lemborexant 15 mg n=6 participants at risk Participants who completed the core study EOS visit within 30 days prior to enrollment in extension phase were eligible to participate in extension phase. Participants received one lemborexant 5 mg and one lemborexant 10 mg, tablets, orally, once daily, immediately (within 5 minutes) before the bedtime at night until lemborexant is commercially available, or until the lemborexant clinical development program for ISWRD is discontinued or up to 30 months.
Cardiac disorders Atrioventricular block first degree	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	7.7% 1/13 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	7.1% 1/14 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Cardiac disorders Bradycardia	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	8.3% 1/12 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	20.0% 1/5 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/14 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Cardiac disorders Palpitations	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	8.3% 1/12 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/14 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Gastrointestinal disorders Constipation	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	7.7% 1/13 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	16.7% 2/12 • Number of events 2 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/14 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	16.7% 1/6 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Gastrointestinal disorders Diarrhoea	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	8.3% 1/12 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	20.0% 1/5 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/14 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	33.3% 2/6 • Number of events 2 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Gastrointestinal disorders Dry mouth	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	8.3% 1/12 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/14 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	16.7% 1/6 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Gastrointestinal disorders Intestinal obstruction	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	8.3% 1/12 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/14 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Infections and infestations Bronchitis	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	7.7% 1/13 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/14 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Infections and infestations Cellulitis	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	8.3% 1/12 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	7.1% 1/14 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Infections and infestations Eye infection	8.3% 1/12 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/14 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Infections and infestations Nasopharyngitis	8.3% 1/12 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	7.7% 1/13 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	28.6% 4/14 • Number of events 4 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	33.3% 2/6 • Number of events 2 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Infections and infestations Urinary tract infection	8.3% 1/12 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/14 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	16.7% 1/6 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	16.7% 2/12 • Number of events 3 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/14 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	16.7% 1/6 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	8.3% 1/12 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/14 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Nervous system disorders Dizziness	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	8.3% 1/12 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	7.1% 1/14 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Nervous system disorders Headache	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	16.7% 2/12 • Number of events 2 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/14 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	16.7% 1/6 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Nervous system disorders Sedation	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	7.7% 1/13 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	20.0% 1/5 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/14 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Nervous system disorders Somnolence	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	7.7% 1/13 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	16.7% 2/12 • Number of events 2 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	60.0% 3/5 • Number of events 3 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/14 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Psychiatric disorders Libido increased	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	7.7% 1/13 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/14 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Psychiatric disorders Nightmare	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	15.4% 2/13 • Number of events 2 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	7.1% 1/14 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Renal and urinary disorders Nephrolithiasis	8.3% 1/12 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/14 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Vascular disorders Hypertension	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	8.3% 1/12 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/14 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Blood and lymphatic system disorders Nephrogenic anaemia	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	7.1% 1/14 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Gastrointestinal disorders Diverticulum	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	7.1% 1/14 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Gastrointestinal disorders Dyspepsia	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	7.1% 1/14 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Infections and infestations Cystitis	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/14 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	16.7% 1/6 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Infections and infestations Otitis media	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	7.1% 1/14 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Infections and infestations Tooth abscess	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/14 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	16.7% 1/6 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Infections and infestations Upper respiratory tract infection	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	14.3% 2/14 • Number of events 2 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Injury, poisoning and procedural complications Contusion	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	20.0% 1/5 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/14 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Injury, poisoning and procedural complications Fall	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	20.0% 1/5 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	14.3% 2/14 • Number of events 2 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	16.7% 1/6 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Injury, poisoning and procedural complications Genital injury	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	7.1% 1/14 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Injury, poisoning and procedural complications Joint injury	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	7.1% 1/14 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Injury, poisoning and procedural complications Laceration	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	7.1% 1/14 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Injury, poisoning and procedural complications Limb injury	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	7.1% 1/14 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Injury, poisoning and procedural complications Upper limb fracture	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	20.0% 1/5 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/14 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Metabolism and nutrition disorders Hypercholesterolaemia	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/14 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	16.7% 1/6 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Musculoskeletal and connective tissue disorders Osteoporosis	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	20.0% 1/5 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/14 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	7.1% 1/14 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Nervous system disorders Syncope	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/14 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	16.7% 1/6 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Psychiatric disorders Anxiety	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	7.1% 1/14 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Psychiatric disorders Delirium	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	20.0% 1/5 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/14 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Psychiatric disorders Depression	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	21.4% 3/14 • Number of events 3 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Psychiatric disorders Irritability	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	20.0% 1/5 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/14 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Renal and urinary disorders Acute kidney injury	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	20.0% 1/5 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/14 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Renal and urinary disorders Chronic kidney disease	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	7.1% 1/14 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Reproductive system and breast disorders Genital discharge	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/13 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/12 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/5 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	7.1% 1/14 • Number of events 1 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)	0.00% 0/6 • First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)

Additional Information

Eisai Medical Information

Eisai Inc.

Phone: 1-888-274-2378

Email: esi_medinfo@eisai.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place