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

Sponsor

Eisai Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT03001557

Collaborator

Purdue Pharma LP (Industry)

Enrollment

Locations

Arms

39.9

Actual Duration (Months)

1.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Irregular Sleep-Wake Rhythm Disorder	Drug: Lemborexant 2.5 mg Drug: Lemborexant 5 mg Drug: Lemborexant 10 mg Drug: Lemborexant 15 mg Drug: Lemborexant-matched placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

63 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 20, 2016

Actual Primary Completion Date :

Jul 26, 2018

Actual Study Completion Date :

Apr 17, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lemborexant 2.5 milligrams (mg) Participants will take one lemborexant 2.5 mg tablet and one lemborexant-matched placebo tablet orally each night for 28 consecutive nights immediately (i.e., within 5 minutes) before the time the participant intends to try to sleep.	Drug: Lemborexant 2.5 mg Lemborexant 2.5 mg tablets Drug: Lemborexant-matched placebo Lemborexant-matched placebo tablets
Experimental: Lemborexant 5 mg Participants will take one lemborexant 5 mg tablet and one lemborexant-matched placebo tablet orally each night for 28 consecutive nights immediately (i.e., within 5 minutes) before the time the participant intends to try to sleep.	Drug: Lemborexant 5 mg Lemborexant 5 mg tablets Drug: Lemborexant-matched placebo Lemborexant-matched placebo tablets
Experimental: Lemborexant 10 mg Participants will take one lemborexant 10 mg tablet and one lemborexant-matched placebo tablet orally each night for 28 consecutive nights immediately (i.e., within 5 minutes) before the time the participant intends to try to sleep.	Drug: Lemborexant 10 mg Lemborexant 10 mg tablets Drug: Lemborexant-matched placebo Lemborexant-matched placebo tablets
Experimental: Lemborexant 15 mg Participants will take one lemborexant 5 mg tablet and one lemborexant 10 mg tablet orally each night for 28 consecutive nights immediately (i.e., within 5 minutes) before the time the participant intends to try to sleep.	Drug: Lemborexant 10 mg Lemborexant 10 mg tablets Drug: Lemborexant 15 mg Lemborexant 5 mg and 10 mg tablets
Placebo Comparator: Lemborexant-matched placebo Participants will take two lemborexant-matched placebo tablets orally each night for 28 consecutive nights immediately (i.e., within 5 minutes) before the time the participant intends to try to sleep.	Drug: Lemborexant-matched placebo Lemborexant-matched placebo tablets

Outcome Measures

Primary Outcome Measures

Core Phase: Change From Baseline in Mean Actigraphy Sleep Efficiency (aSE) With Lemborexant Compared to Placebo During Week 1 of Treatment [Baseline, Week 1]
aSE was defined as the percentage of time spent in bed nocturnal sleeping, as measured by actigraphy. Sleep efficiency was calculated as the total duration of sleep epochs during the predefined 8-hour nocturnal sleep period divided by 8 hours and multiplied by 100. Higher values were better. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average first 7 nights of treatment was reported.
Core Phase: Change From Baseline in Mean aSE With Lemborexant Compared to Placebo During Week 2 of Treatment [Baseline, Week 2]
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.
Core Phase: Change From Baseline in Mean aSE With Lemborexant Compared to Placebo During Week 3 of Treatment [Baseline, Week 3]
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.
Core Phase: Change From Baseline in Mean aSE With Lemborexant Compared to Placebo During Week 4 of Treatment [Baseline, Week 4]
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.
Core Phase: Change From Baseline in Mean Sleep Fragmentation Index (SFI) During Week 1 of Treatment [Baseline, Week 1]
The SFI was defined as the sum of a movement index (MI) and a fragmentation index (FI) during the logged sleep period. The MI was equal to the epochs of wake per time in bed (TBI) multiplied by 100. The FI was equal to the number of less than or equal to (<=) 1-minute periods of immobility/total number of periods of immobility of all durations during the defined nocturnal sleep period multiplied by 100. Value ranges from 0-100 percent (%) (lower values were better). SFI was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average first 7 nights of treatment was reported.
Core Phase: Change From Baseline in Mean SFI During Week 2 of Treatment [Baseline, Week 2]
The SFI was defined as the sum of a MI and a FI during the logged sleep period. The MI was equal to the epochs of wake per TBI multiplied by 100. The FI was equal to the number <=1-minute periods of immobility/total number of periods of immobility of all durations during the defined nocturnal sleep period multiplied by 100. Value ranges from 0-100% (lower values were better). SFI was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average second 7 nights of treatment was reported.
Core Phase: Change From Baseline in Mean SFI During Week 3 of Treatment [Baseline, Week 3]
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.
Core Phase: Change From Baseline in Mean SFI During Week 4 of Treatment [Baseline, Week 4]
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.
Core Phase: Change From Baseline in the Mean Duration of Wake Bouts (aMeanDurWB) During Week 1 of Treatment [Baseline, Week 1]
aMeanDurWB was defined as an average duration of all wake bouts that occurred during the defined nocturnal predefined sleep period. The wake bout was defined as continuous wake of 10 minutes or longer. Lower values were better. aMeanDurWB was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average first 7 nights of treatment was reported.
Core Phase: Change From Baseline in the aMeanDurWB During Week 2 of Treatment [Baseline, Week 2]
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.
Core Phase: Change From Baseline in the aMeanDurWB During Week 3 of Treatment [Baseline, Week 3]
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.
Core Phase: Change From Baseline in the aMeanDurWB During Week 4 of Treatment [Baseline, Week 4]
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.
Core Phase: Change From Baseline in Mean Actigraphy Wake Efficiency (aWE) During Week 1 of Treatment [Baseline, Week 1]
aWE was defined as the percentage of time spent awake in bed during defined wake period, as measured by actigraphy. Wake efficiency was calculated as the total duration of wake epochs during 16 hours outside of the predefined sleep period divided by 16 hours and multiplied by 100. Higher values were better. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average first 7 nights of treatment was reported.
Core Phase: Change From Baseline in Mean aWE During Week 2 of Treatment [Baseline, Week 2]
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.
Core Phase: Change From Baseline in Mean aWE During Week 3 of Treatment [Baseline, Week 3]
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.
Core Phase: Change From Baseline in Mean aWE During Week 4 of Treatment [Baseline, Week 4]
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.
Core Phase: Change From Baseline in Mean Wake Fragmentation Index (WFI) During Week 1 of Treatment [Baseline, Week 1]
The WFI were calculated as the sum of an immobility index (II) and a FI during the logged wake period. The II was equal to the epochs of immobility per the 16 hours outside of the defined sleep period multiplied by 100. The FI was equal to the number of <=1-minute periods of mobility/total number of periods of mobility the 16 hours outside of the defined sleep period multiplied by 100. Value ranges from 0-100 percent (lower values were better). The WFI was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average first 7 nights of treatment was reported.
Core Phase: Change From Baseline in Mean WFI During Week 2 of Treatment [Baseline, Week 2]
The WFI were calculated as the sum of an II and a FI during the logged wake period. The II was equal to the epochs of immobility per the 16 hours outside of the defined sleep period multiplied by 100. The FI was equal to the number of <=1-minute periods of mobility/total number of periods of mobility the 16 hours outside of the defined sleep period multiplied by 100. Value ranges from 0-100% (lower values were better). The WFI was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average second 7 nights of treatment was reported.
Core Phase: Change From Baseline in Mean WFI During Week 3 of Treatment [Baseline, Week 3]
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.
Core Phase: Change From Baseline in Mean WFI During Week 4 of Treatment [Baseline, Week 4]
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.
Core Phase: Change From Baseline in the Mean Duration of Sleep Bouts (aMeanDurSB) During Week 1 of Treatment [Baseline, Week 1]
aMeanDurSB was defined as an average duration of all sleep bouts that occurred during the 16 hours outside of the predefined nocturnal sleep period. The sleep bout was defined as the continuous sleep of 10 minutes or longer. Lower values were better. aMeanDurSB was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average first 7 nights of treatment was reported.
Core Phase: Change From Baseline in the aMeanDurSB During Week 2 of Treatment [Baseline, Week 2]
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.
Core Phase: Change From Baseline in the aMeanDurSB During Week 3 of Treatment [Baseline, Week 3]
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.
Core Phase: Change From Baseline in the aMeanDurSB During Week 4 of Treatment [Baseline, Week 4]
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.
Core Phase: Change From Baseline in Mean Intradaily Variability Over Week 1 of Treatment [Baseline, Week 1]
Intradaily variability gives an indication of irregular sleep-wake rhythm disorder (ISWRD) by quantifying the number and strength of transitions between rest and activity bouts, derived by the ratio of the mean squares of the difference between all successive hours (first derivative) and the mean squares around the grand mean (overall variance). The variable has a theoretical range of 0 to 2, with higher values indicating higher fragmentation. Intradaily variability was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average first 7 nights of treatment was reported.
Core Phase: Change From Baseline in Mean Intradaily Variability Over Week 2 of Treatment [Baseline, Week 2]
Intradaily variability gives an indication of ISWRD by quantifying the number and strength of transitions between rest and activity bouts, derived by the ratio of the mean squares of the difference between all successive hours (first derivative) and the mean squares around the grand mean (overall variance). The variable has a theoretical range of 0 to 2, with higher values indicating higher fragmentation. Intradaily variability was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average second 7 nights of treatment was reported.
Core Phase: Change From Baseline in Mean Intradaily Variability Over Week 3 of Treatment [Baseline, Week 3]
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.
Core Phase: Change From Baseline in Mean Intradaily Variability Over Week 4 of Treatment [Baseline, Week 4]
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.
Core Phase: Change From Baseline in Mean Interdaily Stability (IS) Over Week 1 of Treatment [Baseline, Week 1]
IS gives an indication of the stability of the sleep-wake rhythm across days, and varies from zero (low stability) to 1 (high stability). IS was derived by the ratio between the variance of the average 24-hour pattern around the mean and the overall variance. Higher values indicated stable rhythm. IS was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average first 7 nights of treatment was reported.
Core Phase: Change From Baseline in Mean IS Over Week 2 of Treatment [Baseline, Week 2]
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.
Core Phase: Change From Baseline in Mean IS Over Week 3 of Treatment [Baseline, Week 3]
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.
Core Phase: Change From Baseline in Mean IS Over Week 4 of Treatment [Baseline, Week 4]
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.
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, Week 1]
L5 was defined as the average activity across the least active 5-hour period per 24-hour period, with high values indicating restlessness. This value provides an indication of how restful (inactive) and regular the sleep periods are. L5 was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average first 7 nights of treatment was reported.
Core Phase: Change From Baseline in Average Activity Counts Across L5 Per 24-Hour Period Over Week 2 of Treatment [Baseline, Week 2]
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.
Core Phase: Change From Baseline in Average Activity Counts Across L5 Per 24-Hour Period Over Week 3 of Treatment [Baseline, Week 3]
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.
Core Phase: Change From Baseline in Average Activity Counts Across L5 Per 24-Hour Period Over Week 4 of Treatment [Baseline, Week 4]
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.
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, Week 1]
M10 was defined as the average activity during the most active 10-hour period per 24-hour period with low levels indicating inactivity. M10 was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average first 7 nights of treatment was reported.
Core Phase: Change From Baseline in the Average Activity Count During the M10 Per 24-Hour Period Over Week 2 of Treatment [Baseline, Week 2]
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.
Core Phase: Change From Baseline in the Average Activity Count During the M10 Per 24-Hour Period Over Week 3 of Treatment [Baseline, Week 3]
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.
Core Phase: Change From Baseline in the Average Activity Count During the M10 Per 24-Hour Period Over Week 4 of Treatment [Baseline, Week 4]
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.
Core Phase: Change From Baseline in Amplitude of the Rest-activity Rhythm (AMP) Over Week 1 of Treatment [Baseline, Week 1]
AMP was amplitude of rest-activity rhythm calculated as the difference between M10 and L5. L5 was defined as the average activity across the least active 5-hour period per 24-hour period, with high values indicating restlessness. M10 was defined as the average activity during the most active 10-hour period per 24-hour period with low levels indicating inactivity. AMP was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average first 7 nights of treatment was reported.
Core Phase: Change From Baseline in AMP Over Week 2 of Treatment [Baseline, Week 2]
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.
Core Phase: Change From Baseline in AMP Over Week 3 of Treatment [Baseline, Week 3]
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.
Core Phase: Change From Baseline in AMP Over Week 4 of Treatment [Baseline, Week 4]
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.
Core Phase: Change From Baseline in Relative Amplitude in the Rest-activity Rhythm (RA) Over Week 1 of Treatment [Baseline, Week 1]
RA was relative amplitude of the rest-activity rhythm calculated as the difference between M10 and L5 divided by M10 plus L5. L5 was defined as the average activity across the least active 5-hour period per 24-hour period, with high values indicating restlessness. M10 was defined as the average activity during the most active 10-hour period per 24-hour period with low levels indicating inactivity. RA was determined by Actigraphy. Actigraphy was performed with an accelerometer that was worn on the wrist like a watch. It was programmed to monitor degree and intensity of movements while the device was being worn. Change from baseline to average first 7 nights of treatment was reported.
Core Phase: Change From Baseline in RA Over Week 2 of Treatment [Baseline, Week 2]
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.
Core Phase: Change From Baseline in RA Over Week 3 of Treatment [Baseline, Week 3]
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.
Core Phase: Change From Baseline in RA Over Week 4 of Treatment [Baseline, Week 4]
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.

Other Outcome Measures

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 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 [Day 29]
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]).
Core Phase: Change From Baseline in the Neuropsychiatric Inventory (NPI-10) Total Score at Day 29 [Baseline, Day 29]
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.
Core Phase: Change From Baseline in the Sleep Disorders Inventory (SDI) Score at Day 29 [Baseline, Day 29]
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]).
Extension Phase: Change From Baseline in SDI Total Score. [Baseline, Day 133, 223, 313, 343, 373, 403, 493, 583, 673, and 763]
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]).

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria (Core Study):

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

Inclusion Criteria (Extension Phase):

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

Inclusion Criteria for Caregivers:

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

Exclusion Criteria:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Facility #1	Little Rock	Arkansas	United States	72205
2	Facility #1	Rogers	Arkansas	United States	72758
3	Facility #1	Costa Mesa	California	United States	92626
4	Facility #1	Fullerton	California	United States	92835
5	Facility #1	Glendale	California	United States	91206
6	Facility #1	Irvine	California	United States	92614
7	Facility #1	Irvine	California	United States	92618
8	Facility #1	La Jolla	California	United States	92037-0949
9	Facility #1	San Diego	California	United States	92103
10	Facility #1	Santa Monica	California	United States	90404
11	Facility #1	Bradenton	Florida	United States	34205
12	Facility #1	Brandon	Florida	United States	33511
13	Facility #1	Brooksville	Florida	United States	34601
14	Facility #1	Hallandale Beach	Florida	United States	33009
15	Facility #1	Miami Lakes	Florida	United States	33014
16	Facility #1	Miami Springs	Florida	United States	33016
17	Facility #1	Miami	Florida	United States	33137
18	Facility #1	Miami	Florida	United States	33165
19	Facility #1	Orlando	Florida	United States	32806
20	Facility #2	Orlando	Florida	United States	32806
21	Facility #1	Sunrise	Florida	United States	33351
22	Facility #2	Tampa	Florida	United States	33613
23	Facility #1	Atlanta	Georgia	United States	30331
24	Facility #1	Columbus	Georgia	United States	31909
25	Facility #1	Macon	Georgia	United States	31201
26	Facility #1	Wichita	Kansas	United States	67207
27	Facility #1	Belmont	Massachusetts	United States	02478
28	Nevada Senior Services (NSS) Adult Day Care Center	Henderson	Nevada	United States
29	Facility #1	Las Vegas	Nevada	United States	89104
30	Facility #1	Toms River	New Jersey	United States	08755
31	Facility #2	Toms River	New Jersey	United States	08755
32	Facility #1	Charlotte	North Carolina	United States	28270
33	Facility #2	Durham	North Carolina	United States	27705
34	Facility #1	Raleigh	North Carolina	United States	27612
35	Facility #1	Norristown	Pennsylvania	United States	19401
36	Facility #1	Willow Grove	Pennsylvania	United States	19090
37	Facility #1	Columbia	South Carolina	United States	29203
38	Eisai Trial Site #1	Nagoya	Aichi	Japan	451-8511
39	Eisai Trial Site #1	Fujisawa	Kanagawa	Japan	251-0038
40	Eisai Trial Site #1	Kawasaki-shi	Kanagawa	Japan	210-0852
41	Eisai Trial Site #1	Wako	Saitama	Japan	351-0111
42	Eisai Trial Site #1	Kodaira	Tokyo	Japan	187-8551
43	Eisai Trial Site #1	Setagaya	Tokyo	Japan	156-0041
44	Eisai Trial Site #1	Shinjuku	Tokyo	Japan	169-0073
45	Eisai Trial Site #1	Tachikawa-shi	Tokyo	Japan	190-8531
46	Brighton and Sussex Medical School	Brighton	East Sussex	United Kingdom	BN1 9PX
47	Cognitive Treatment and Research Unit	Crowborough	East Sussex	United Kingdom	TN6 1NY
48	University of Edinburgh - PPDS	Edinburgh		United Kingdom	EH1 64UX

Sponsors and Collaborators

Eisai Inc.
Purdue Pharma LP

Investigators

None specified.

Study Documents (Full-Text)

More Information

Publications

None provided.

Responsible Party:

Eisai Inc.

ClinicalTrials.gov Identifier:

NCT03001557

Other Study ID Numbers:

E2006-G000-202
2017-003306-40

First Posted:

Dec 23, 2016

Last Update Posted:

May 17, 2021

Last Verified:

Apr 1, 2021

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Eisai Inc.

Mild to Moderate Alzheimer's Disease Dementia

sleep

circadian rhythms

Additional relevant MeSH terms:

Alzheimer Disease

Dementia

Lemborexant

Study Results

Participant Flow

Recruitment Details

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.

Pre-assignment Detail

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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg	Extension Phase: Lemborexant 5 mg	Extension Phase: Lemborexant 10 mg	Extension Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	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.
Period Title: Core Phase
STARTED	12	12	14	13	12	0	0	0
Treated	12	12	13	13	12	0	0	0
COMPLETED	12	12	13	13	12	0	0	0
NOT COMPLETED	0	0	1	0	0	0	0	0
Period Title: Core Phase
STARTED	0	0	0	0	0	5	14	6
COMPLETED	0	0	0	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	5	14	6

Baseline Characteristics

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg	Total
Arm/Group Description	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.	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.	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.	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.	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 of all reporting groups
Overall Participants	12	12	13	13	12	62
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	75.3 (6.15)	76.5 (6.32)	76.9 (7.98)	71.8 (7.05)	71.9 (6.11)	74.5 (6.94)
Sex: Female, Male (Count of Participants)
Female	7 58.3%	6 50%	8 61.5%	6 46.2%	10 83.3%	37 59.7%
Male	5 41.7%	6 50%	5 38.5%	7 53.8%	2 16.7%	25 40.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 33.3%	2 16.7%	4 30.8%	6 46.2%	8 66.7%	24 38.7%
Not Hispanic or Latino	8 66.7%	10 83.3%	9 69.2%	7 53.8%	4 33.3%	38 61.3%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	2 16.7%	2 16.7%	2 15.4%	3 23.1%	2 16.7%	11 17.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	2 16.7%	1 8.3%	2 15.4%	1 7.7%	1 8.3%	7 11.3%
White	8 66.7%	9 75%	8 61.5%	9 69.2%	9 75%	43 69.4%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	1 7.7%	0 0%	0 0%	1 1.6%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	76.34 (6.559)	77.64 (7.883)	78.45 (6.844)	76.38 (8.037)	77.35 (8.624)
Change at Week 1	0.14 (5.766)	2.43 (3.910)	3.87 (4.646)	-0.17 (5.861)	0.05 (4.475)

2. Primary Outcome

Title	Core Phase: Change From Baseline in Mean aSE With Lemborexant Compared to Placebo During Week 2 of Treatment
Description	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.
Time Frame	Baseline, Week 2

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	76.34 (6.559)	77.64 (7.883)	78.45 (6.844)	76.38 (8.037)	77.35 (8.624)
Change at Week 2	-1.31 (7.004)	2.17 (2.833)	1.65 (4.644)	-1.41 (5.896)	-0.07 (5.449)

3. Primary Outcome

Title	Core Phase: Change From Baseline in Mean aSE With Lemborexant Compared to Placebo During Week 3 of Treatment
Description	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.
Time Frame	Baseline, Week 3

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	76.34 (6.559)	77.64 (7.883)	78.45 (6.844)	76.38 (8.037)	77.35 (8.624)
Change at Week 3	-0.30 (10.552)	1.68 (3.229)	0.91 (7.571)	-1.49 (4.442)	1.10 (7.112)

4. Primary Outcome

Title	Core Phase: Change From Baseline in Mean aSE With Lemborexant Compared to Placebo During Week 4 of Treatment
Description	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.
Time Frame	Baseline, Week 4

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	76.34 (6.559)	77.64 (7.883)	78.45 (6.844)	76.38 (8.037)	77.35 (8.624)
Change at Week 4	-0.78 (9.555)	1.68 (4.696)	0.00 (5.547)	-1.04 (5.920)	-0.81 (7.735)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 2.5 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.1099
	Comments	Based on a mixed model for repeated measure (MMRM) analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	Least square mean (LSM) difference
	Estimated Value	3.177
	Confidence Interval	(2-Sided) 95% -0.741 to 7.096
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 5 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.1576
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	2.802
	Confidence Interval	(2-Sided) 95% -1.119 to 6.723
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 10 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.6160
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	-0.960
	Confidence Interval	(2-Sided) 95% -4.777 to 2.857
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 15 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.7135
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	0.713
	Confidence Interval	(2-Sided) 95% -3.160 to 4.585
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Primary Outcome

Title	Core Phase: Change From Baseline in Mean Sleep Fragmentation Index (SFI) During Week 1 of Treatment
Description	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.
Time Frame	Baseline, Week 1

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	58.51 (12.923)	53.87 (17.594)	50.07 (12.493)	54.75 (16.380)	54.78 (15.338)
Change at Week 1	-1.43 (9.294)	-5.80 (11.388)	-8.16 (8.802)	-2.55 (11.756)	-3.52 (8.882)

6. Primary Outcome

Title	Core Phase: Change From Baseline in Mean SFI During Week 2 of Treatment
Description	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.
Time Frame	Baseline, Week 2

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	58.51 (12.923)	53.87 (17.594)	50.07 (12.493)	54.75 (16.380)	54.78 (15.338)
Change at Week 2	2.52 (11.845)	-6.91 (5.994)	-4.95 (8.399)	0.34 (14.194)	-3.18 (8.971)

7. Primary Outcome

Title	Core Phase: Change From Baseline in Mean SFI During Week 3 of Treatment
Description	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.
Time Frame	Baseline, Week 3

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	58.51 (12.923)	53.87 (17.594)	50.07 (12.493)	54.75 (16.380)	54.78 (15.338)
Change at Week 3	-3.30 (18.512)	-2.79 (7.541)	-5.22 (11.974)	0.36 (9.018)	-4.92 (9.572)

8. Primary Outcome

Title	Core Phase: Change From Baseline in Mean SFI During Week 4 of Treatment
Description	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.
Time Frame	Baseline, Week 4

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	58.51 (12.923)	53.87 (17.594)	50.07 (12.493)	54.75 (16.380)	54.78 (15.338)
Change at Week 4	-1.39 (19.383)	-1.35 (8.821)	-1.96 (8.459)	-0.45 (13.389)	-1.68 (12.683)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 2.5 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.1582
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	-5.098
	Confidence Interval	(2-Sided) 95% -12.240 to 2.045
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 5 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0961
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	-6.105
	Confidence Interval	(2-Sided) 95% -13.332 to 1.122
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 10 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.8449
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	0.680
	Confidence Interval	(2-Sided) 95% -6.262 to 7.623
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 15 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.3747
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	-3.140
	Confidence Interval	(2-Sided) 95% -10.178 to 3.897
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Primary Outcome

Title	Core Phase: Change From Baseline in the Mean Duration of Wake Bouts (aMeanDurWB) During Week 1 of Treatment
Description	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.
Time Frame	Baseline, Week 1

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	20.32 (6.625)	20.40 (5.140)	20.62 (5.898)	21.89 (4.885)	21.94 (7.790)
Change at Week 1	-1.65 (5.078)	-1.99 (2.825)	-0.51 (6.522)	-0.82 (5.722)	1.54 (5.378)

10. Primary Outcome

Title	Core Phase: Change From Baseline in the aMeanDurWB During Week 2 of Treatment
Description	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.
Time Frame	Baseline, Week 2

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	20.32 (6.625)	20.40 (5.140)	20.62 (5.898)	21.89 (4.885)	21.94 (7.790)
Change at Week 2	-0.32 (7.904)	1.79 (12.957)	4.71 (13.845)	1.54 (6.333)	2.57 (6.708)

11. Primary Outcome

Title	Core Phase: Change From Baseline in the aMeanDurWB During Week 3 of Treatment
Description	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.
Time Frame	Baseline, Week 3

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	20.32 (6.625)	20.40 (5.140)	20.62 (5.898)	21.89 (4.885)	21.94 (7.790)
Change at Week 3	-2.88 (7.928)	3.67 (7.833)	-0.52 (4.595)	-0.64 (5.482)	2.76 (7.489)

12. Primary Outcome

Title	Core Phase: Change From Baseline in the aMeanDurWB During Week 4 of Treatment
Description	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.
Time Frame	Baseline, Week 4

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	20.32 (6.625)	20.40 (5.140)	20.62 (5.898)	21.89 (4.885)	21.94 (7.790)
Change at Week 4	-1.26 (8.621)	-0.43 (8.053)	3.16 (8.140)	-2.03 (4.947)	3.38 (12.354)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 2.5 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.3966
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	1.932
	Confidence Interval	(2-Sided) 95% -2.601 to 6.465
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 5 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.1381
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	3.386
	Confidence Interval	(2-Sided) 95% -1.125 to 7.897
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 10 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.5487
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	1.337
	Confidence Interval	(2-Sided) 95% -3.104 to 5.778
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 15 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0581
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	4.320
	Confidence Interval	(2-Sided) 95% -0.153 to 8.793
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Primary Outcome

Title	Core Phase: Change From Baseline in Mean Actigraphy Wake Efficiency (aWE) During Week 1 of Treatment
Description	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.
Time Frame	Baseline, Week 1

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	69.74 (12.609)	70.57 (11.669)	72.53 (11.473)	67.19 (11.523)	70.67 (11.221)
Change at Week 1	0.59 (4.177)	-2.41 (6.726)	1.09 (6.793)	-1.55 (9.216)	-2.37 (8.779)

14. Primary Outcome

Title	Core Phase: Change From Baseline in Mean aWE During Week 2 of Treatment
Description	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.
Time Frame	Baseline, Week 2

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	69.74 (12.609)	70.57 (11.669)	72.53 (11.473)	67.19 (11.523)	70.67 (11.221)
Change at Week 2	2.14 (2.773)	-1.54 (6.550)	1.04 (7.511)	-3.16 (12.816)	-0.63 (5.617)

15. Primary Outcome

Title	Core Phase: Change From Baseline in Mean aWE During Week 3 of Treatment
Description	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.
Time Frame	Baseline, Week 3

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	69.74 (12.609)	70.57 (11.669)	72.53 (11.473)	67.19 (11.523)	70.67 (11.221)
Change at Week 3	1.64 (5.451)	-2.37 (6.239)	2.34 (8.370)	-4.99 (11.479)	-1.83 (5.579)

16. Primary Outcome

Title	Core Phase: Change From Baseline in Mean aWE During Week 4 of Treatment
Description	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.
Time Frame	Baseline, Week 4

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	69.74 (12.609)	70.57 (11.669)	72.53 (11.473)	67.19 (11.523)	70.67 (11.221)
Change at Week 4	2.03 (6.841)	-2.29 (7.724)	3.62 (8.586)	-2.65 (9.627)	-0.43 (5.848)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 2.5 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.1777
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	-3.437
	Confidence Interval	(2-Sided) 95% -8.481 to 1.608
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 5 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.5630
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	1.458
	Confidence Interval	(2-Sided) 95% -3.564 to 6.479
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 10 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0482
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	-4.994
	Confidence Interval	(2-Sided) 95% -9.946 to -0.041
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 15 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.3036
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	-2.593
	Confidence Interval	(2-Sided) 95% -7.599 to 2.413
	Parameter Dispersion	Type: Value:
	Estimation Comments

17. Primary Outcome

Title	Core Phase: Change From Baseline in Mean Wake Fragmentation Index (WFI) During Week 1 of Treatment
Description	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.
Time Frame	Baseline, Week 1

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	92.43 (18.547)	85.72 (16.137)	86.53 (18.705)	94.76 (17.262)	87.96 (15.928)
Change at Week 1	-0.14 (6.968)	4.22 (9.988)	-2.18 (10.571)	2.01 (13.017)	3.25 (13.006)

18. Primary Outcome

Title	Core Phase: Change From Baseline in Mean WFI During Week 2 of Treatment
Description	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.
Time Frame	Baseline, Week 2

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	92.43 (18.547)	85.72 (16.137)	86.53 (18.705)	94.76 (17.262)	87.96 (15.928)
Change at Week 2	-3.76 (3.940)	4.12 (8.671)	-2.36 (11.453)	5.09 (19.006)	1.78 (9.271)

19. Primary Outcome

Title	Core Phase: Change From Baseline in Mean WFI During Week 3 of Treatment
Description	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.
Time Frame	Baseline, Week 3

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	92.43 (18.547)	85.72 (16.137)	86.53 (18.705)	94.76 (17.262)	87.96 (15.928)
Change at Week 3	-1.65 (7.980)	4.70 (9.674)	-3.69 (13.236)	6.88 (16.704)	2.10 (8.631)

20. Primary Outcome

Title	Core Phase: Change From Baseline in Mean WFI During Week 4 of Treatment
Description	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.
Time Frame	Baseline, Week 4

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	92.43 (18.547)	85.72 (16.137)	86.53 (18.705)	94.76 (17.262)	87.96 (15.928)
Change at Week 4	-3.01 (10.620)	4.55 (10.930)	-6.93 (14.428)	2.77 (13.407)	1.22 (8.054)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 2.5 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.1991
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	4.845
	Confidence Interval	(2-Sided) 95% -2.624 to 12.313
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 5 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.2982
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	-3.872
	Confidence Interval	(2-Sided) 95% -11.263 to 3.518
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 10 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0664
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	6.776
	Confidence Interval	(2-Sided) 95% -0.474 to 14.025
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 15 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.4148
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	3.017
	Confidence Interval	(2-Sided) 95% -4.344 to 10.379
	Parameter Dispersion	Type: Value:
	Estimation Comments

21. Primary Outcome

Title	Core Phase: Change From Baseline in the Mean Duration of Sleep Bouts (aMeanDurSB) During Week 1 of Treatment
Description	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.
Time Frame	Baseline, Week 1

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	18.36 (4.620)	20.65 (3.638)	23.13 (5.919)	19.84 (3.364)	23.30 (10.862)
Change at Week 1	2.15 (2.539)	0.09 (4.056)	-1.12 (5.202)	-0.40 (3.394)	-3.19 (10.405)

22. Primary Outcome

Title	Core Phase: Change From Baseline in the aMeanDurSB During Week 2 of Treatment
Description	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.
Time Frame	Baseline, Week 2

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	18.36 (4.620)	20.65 (3.638)	23.13 (5.919)	19.84 (3.364)	23.30 (10.862)
Change at Week 2	0.25 (2.999)	-0.88 (4.679)	-2.52 (5.965)	-0.80 (2.961)	-3.95 (8.980)

23. Primary Outcome

Title	Core Phase: Change From Baseline in the aMeanDurSB During Week 3 of Treatment
Description	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.
Time Frame	Baseline, Week 3

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	18.36 (4.620)	20.65 (3.638)	23.13 (5.919)	19.84 (3.364)	23.30 (10.862)
Change at Week 3	-0.14 (3.249)	-1.17 (4.056)	-3.80 (3.701)	-0.68 (2.292)	-4.15 (10.264)

24. Primary Outcome

Title	Core Phase: Change From Baseline in the aMeanDurSB During Week 4 of Treatment
Description	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.
Time Frame	Baseline, Week 4

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	18.36 (4.620)	20.65 (3.638)	23.13 (5.919)	19.84 (3.364)	23.30 (10.862)
Change at Week 4	1.00 (4.568)	-1.31 (3.639)	-2.80 (5.727)	-0.03 (2.307)	-5.30 (9.745)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 2.5 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.9599
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	0.063
	Confidence Interval	(2-Sided) 95% -2.452 to 2.579
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 5 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.8541
	Comments	Based on a MMRM analysis adjusted for baseline value, country, Visit and treatment by Visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	-0.238
	Confidence Interval	(2-Sided) 95% -2.817 to 2.342
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 10 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.8117
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	-0.293
	Confidence Interval	(2-Sided) 95% -2.745 to 2.160
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 15 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.2274
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	-1.557
	Confidence Interval	(2-Sided) 95% -4.113 to 1.000
	Parameter Dispersion	Type: Value:
	Estimation Comments

25. Primary Outcome

Title	Core Phase: Change From Baseline in Mean Intradaily Variability Over Week 1 of Treatment
Description	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.
Time Frame	Baseline, Week 1

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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	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.	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.
Measure Participants	12	12	13	13	12
Baseline	1.10 (0.262)	0.90 (0.272)	0.98 (0.295)	1.10 (0.295)	1.03 (0.330)
Change at Week 1	-0.01 (0.200)	0.06 (0.218)	-0.03 (0.237)	0.10 (0.271)	-0.01 (0.278)

26. Primary Outcome

Title	Core Phase: Change From Baseline in Mean Intradaily Variability Over Week 2 of Treatment
Description	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.
Time Frame	Baseline, Week 2

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	1.10 (0.262)	0.90 (0.272)	0.98 (0.295)	1.10 (0.295)	1.03 (0.330)
Change at Week 2	-0.05 (0.132)	0.14 (0.325)	0.02 (0.235)	0.07 (0.143)	0.05 (0.234)

27. Primary Outcome

Title	Core Phase: Change From Baseline in Mean Intradaily Variability Over Week 3 of Treatment
Description	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.
Time Frame	Baseline, Week 3

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	1.10 (0.262)	0.90 (0.272)	0.98 (0.295)	1.10 (0.295)	1.03 (0.330)
Change at Week 3	-0.06 (0.243)	0.07 (0.246)	-0.00 (0.241)	-0.06 (0.311)	-0.01 (0.219)

28. Primary Outcome

Title	Core Phase: Change From Baseline in Mean Intradaily Variability Over Week 4 of Treatment
Description	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.
Time Frame	Baseline, Week 4

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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	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.	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.
Measure Participants	12	12	13	13	12
Baseline	1.10 (0.262)	0.90 (0.272)	0.98 (0.295)	1.10 (0.295)	1.03 (0.330)
Change at Week 4	-0.10 (0.324)	0.10 (0.196)	0.02 (0.157)	-0.12 (0.274)	-0.10 (0.222)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 2.5 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.2421
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	0.086
	Confidence Interval	(2-Sided) 95% -0.060 to 0.232
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 5 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.8661
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	-0.012
	Confidence Interval	(2-Sided) 95% -0.155 to 0.131
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 10 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.4251
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	0.057
	Confidence Interval	(2-Sided) 95% -0.085 to 0.199
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 15 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.7248
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	0.025
	Confidence Interval	(2-Sided) 95% -0.116 to 0.166
	Parameter Dispersion	Type: Value:
	Estimation Comments

29. Primary Outcome

Title	Core Phase: Change From Baseline in Mean Interdaily Stability (IS) Over Week 1 of Treatment
Description	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.
Time Frame	Baseline, Week 1

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	0.45 (0.173)	0.47 (0.111)	0.49 (0.118)	0.46 (0.160)	0.41 (0.104)
Change at Week 1	0.04 (0.083)	-0.02 (0.089)	0.04 (0.115)	-0.00 (0.155)	0.06 (0.063)

30. Primary Outcome

Title	Core Phase: Change From Baseline in Mean IS Over Week 2 of Treatment
Description	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.
Time Frame	Baseline, Week 2

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	0.45 (0.173)	0.47 (0.111)	0.49 (0.118)	0.46 (0.160)	0.41 (0.104)
Change at Week 2	0.06 (0.093)	-0.01 (0.101)	0.03 (0.133)	-0.06 (0.091)	0.09 (0.085)

31. Primary Outcome

Title	Core Phase: Change From Baseline in Mean IS Over Week 3 of Treatment
Description	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.
Time Frame	Baseline, Week 3

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	0.45 (0.173)	0.47 (0.111)	0.49 (0.118)	0.46 (0.160)	0.41 (0.104)
Change at Week 3	0.03 (0.104)	-0.01 (0.107)	0.03 (0.115)	-0.04 (0.136)	0.04 (0.075)

32. Primary Outcome

Title	Core Phase: Change From Baseline in Mean IS Over Week 4 of Treatment
Description	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.
Time Frame	Baseline, Week 4

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	0.45 (0.173)	0.47 (0.111)	0.49 (0.118)	0.46 (0.160)	0.41 (0.104)
Change at Week 4	0.02 (0.098)	0.01 (0.119)	0.08 (0.092)	0.03 (0.127)	0.00 (0.102)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 2.5 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.2991
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	-0.032
	Confidence Interval	(2-Sided) 95% -0.094 to 0.029
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 5 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.2861
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	0.033
	Confidence Interval	(2-Sided) 95% -0.028 to 0.095
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 10 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0938
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	-0.052
	Confidence Interval	(2-Sided) 95% -0.113 to 0.009
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 15 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.8618
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	0.005
	Confidence Interval	(2-Sided) 95% -0.055 to 0.066
	Parameter Dispersion	Type: Value:
	Estimation Comments

33. Primary Outcome

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

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	1163.5 (373.3)	1266.4 (678.1)	1163.2 (591.8)	1257.1 (836.6)	1490.4 (963.1)
Change at Week 1	200.9 (633.3)	-259.8 (450.3)	-243.2 (333.6)	-211.6 (378.3)	-434.2 (509.1)

34. Primary Outcome

Title	Core Phase: Change From Baseline in Average Activity Counts Across L5 Per 24-Hour Period Over Week 2 of Treatment
Description	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.
Time Frame	Baseline, Week 2

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	1163.5 (373.3)	1266.4 (678.1)	1163.2 (591.8)	1257.1 (836.6)	1490.4 (963.1)
Change at Week 2	85.8 (525.3)	-259.8 (244.9)	-218.7 (321.6)	218.5 (455.9)	-246.1 (637.6)

35. Primary Outcome

Title	Core Phase: Change From Baseline in Average Activity Counts Across L5 Per 24-Hour Period Over Week 3 of Treatment
Description	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.
Time Frame	Baseline, Week 3

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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	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.	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.
Measure Participants	12	12	13	13	12
Baseline	1163.5 (373.3)	1266.4 (678.1)	1163.2 (591.8)	1257.1 (836.6)	1490.4 (963.1)
Change at Week 3	299.2 (1070.2)	-265.3 (507.0)	-233.0 (369.3)	-114.6 (376.6)	-396.1 (543.9)

36. Primary Outcome

Title	Core Phase: Change From Baseline in Average Activity Counts Across L5 Per 24-Hour Period Over Week 4 of Treatment
Description	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.
Time Frame	Baseline, Week 4

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	1163.5 (373.3)	1266.4 (678.1)	1163.2 (591.8)	1257.1 (836.6)	1490.4 (963.1)
Change at Week 4	293.1 (662.6)	-334.0 (476.4)	-344.5 (419.1)	30.5 (772.5)	-160.7 (471.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 2.5 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0294
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	-389.873
	Confidence Interval	(2-Sided) 95% -739.177 to -40.569
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 5 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0243
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	-402.994
	Confidence Interval	(2-Sided) 95% -751.670 to -54.319
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 10 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.4209
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	-141.026
	Confidence Interval	(2-Sided) 95% -489.805 to 207.752
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 15 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0398
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	-367.845
	Confidence Interval	(2-Sided) 95% -717.870 to -17.820
	Parameter Dispersion	Type: Value:
	Estimation Comments

37. Primary Outcome

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

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	8560.4 (2631.2)	11567.0 (4266.3)	12158.1 (3639.9)	10662.1 (5023.6)	11460.5 (4954.3)
Change at Week 1	59.7 (1832.6)	-731.4 (3373.5)	42.5 (1789.3)	-334.6 (2659.2)	-111.2 (2558.0)

38. Primary Outcome

Title	Core Phase: Change From Baseline in the Average Activity Count During the M10 Per 24-Hour Period Over Week 2 of Treatment
Description	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.
Time Frame	Baseline, Week 2

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	8560.4 (2631.2)	11567.0 (4266.3)	12158.1 (3639.9)	10662.1 (5023.6)	11460.5 (4954.3)
Change at Week 2	232.7 (1829.1)	-968.8 (2885.6)	-121.1 (2137.3)	-564.2 (1975.7)	-325.4 (1585.4)

39. Primary Outcome

Title	Core Phase: Change From Baseline in the Average Activity Count During the M10 Per 24-Hour Period Over Week 3 of Treatment
Description	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.
Time Frame	Baseline, Week 3

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	8560.4 (2631.2)	11567.0 (4266.3)	12158.1 (3639.9)	10662.1 (5023.6)	11460.5 (4954.3)
Change at Week 3	300.3 (2094.9)	-986.2 (3502.0)	572.6 (2216.0)	-828.3 (1970.2)	-635.8 (2413.6)

40. Primary Outcome

Title	Core Phase: Change From Baseline in the Average Activity Count During the M10 Per 24-Hour Period Over Week 4 of Treatment
Description	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.
Time Frame	Baseline, Week 4

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	8560.4 (2631.2)	11567.0 (4266.3)	12158.1 (3639.9)	10662.1 (5023.6)	11460.5 (4954.3)
Change at Week 4	1650.4 (1815.3)	-1392.1 (2249.3)	-477.4 (963.2)	279.8 (2204.0)	-457.8 (1788.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 2.5 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.1162
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	-1276.180
	Confidence Interval	(2-Sided) 95% -2878.587 to 326.226
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 5 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.7781
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	227.464
	Confidence Interval	(2-Sided) 95% -1382.850 to 1837.777
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 10 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.4255
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	-620.581
	Confidence Interval	(2-Sided) 95% -2170.342 to 929.179
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 15 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.4672
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	-577.820
	Confidence Interval	(2-Sided) 95% -2160.337 to 1004.697
	Parameter Dispersion	Type: Value:
	Estimation Comments

41. Primary Outcome

Title	Core Phase: Change From Baseline in Amplitude of the Rest-activity Rhythm (AMP) Over Week 1 of Treatment
Description	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.
Time Frame	Baseline, Week 1

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	7396.9 (2728.3)	10300.6 (4235.8)	10994.8 (3601.8)	9405.0 (5133.9)	9970.0 (4905.8)
Change at Week 1	-141.1 (1583.8)	-471.6 (3414.4)	285.8 (1788.6)	-123.0 (2784.1)	323.0 (2436.0)

42. Primary Outcome

Title	Core Phase: Change From Baseline in AMP Over Week 2 of Treatment
Description	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.
Time Frame	Baseline, Week 2

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	7396.9 (2728.3)	10300.6 (4235.8)	10994.8 (3601.8)	9405.0 (5133.9)	9970.0 (4905.8)
Change at Week 2	146.8 (1603.7)	-708.9 (2934.6)	97.6 (2105.2)	-782.7 (2141.4)	-79.3 (1672.5)

43. Primary Outcome

Title	Core Phase: Change From Baseline in AMP Over Week 3 of Treatment
Description	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.
Time Frame	Baseline, Week 3

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	7396.9 (2728.3)	10300.6 (4235.8)	10994.8 (3601.8)	9405.0 (5133.9)	9970.0 (4905.8)
Change at Week 3	1.1 (1862.7)	-721.0 (3502.2)	805.6 (2195.6)	-713.7 (2178.3)	-239.7 (2592.5)

44. Primary Outcome

Title	Core Phase: Change From Baseline in AMP Over Week 4 of Treatment
Description	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.
Time Frame	Baseline, Week 4

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	7396.9 (2728.3)	10300.6 (4235.8)	10994.8 (3601.8)	9405.0 (5133.9)	9970.0 (4905.8)
Change at Week 4	1357.3 (1801.9)	-1058.0 (2170.9)	-132.9 (840.7)	249.4 (2694.7)	-297.1 (1608.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 2.5 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.2984
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	-839.088
	Confidence Interval	(2-Sided) 95% -2440.854 to 762.678
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 5 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.4218
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	651.922
	Confidence Interval	(2-Sided) 95% -962.835 to 2266.678
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 10 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.5655
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	-447.245
	Confidence Interval	(2-Sided) 95% -1998.440 to 1103.950
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 15 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.8686
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	-130.603
	Confidence Interval	(2-Sided) 95% -1706.478 to 1445.272
	Parameter Dispersion	Type: Value:
	Estimation Comments

45. Primary Outcome

Title	Core Phase: Change From Baseline in Relative Amplitude in the Rest-activity Rhythm (RA) Over Week 1 of Treatment
Description	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.
Time Frame	Baseline, Week 1

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	0.73 (0.136)	0.79 (0.141)	0.82 (0.089)	0.77 (0.165)	0.76 (0.148)
Change at Week 1	-0.02 (0.101)	0.01 (0.080)	0.03 (0.067)	0.02 (0.096)	0.07 (0.073)

46. Primary Outcome

Title	Core Phase: Change From Baseline in RA Over Week 2 of Treatment
Description	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.
Time Frame	Baseline, Week 2

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	0.73 (0.136)	0.79 (0.141)	0.82 (0.089)	0.77 (0.165)	0.76 (0.148)
Change at Week 2	-0.00 (0.073)	0.01 (0.063)	0.03 (0.052)	-0.05 (0.112)	0.05 (0.091)

47. Primary Outcome

Title	Core Phase: Change From Baseline in RA Over Week 3 of Treatment
Description	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.
Time Frame	Baseline, Week 3

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	0.73 (0.136)	0.79 (0.141)	0.82 (0.089)	0.77 (0.165)	0.76 (0.148)
Change at Week 3	-0.01 (0.143)	0.01 (0.088)	0.04 (0.063)	0.01 (0.090)	0.06 (0.080)

48. Primary Outcome

Title	Core Phase: Change From Baseline in RA Over Week 4 of Treatment
Description	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.
Time Frame	Baseline, Week 4

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	0.73 (0.136)	0.79 (0.141)	0.82 (0.089)	0.77 (0.165)	0.76 (0.148)
Change at Week 4	-0.00 (0.117)	0.01 (0.060)	0.05 (0.049)	0.01 (0.136)	0.02 (0.069)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 2.5 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.4638
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	0.020
	Confidence Interval	(2-Sided) 95% -0.034 to 0.074
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 5 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0322
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	0.060
	Confidence Interval	(2-Sided) 95% 0.005 to 0.115
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 10 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.9144
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction.
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	0.003
	Confidence Interval	(2-Sided) 95% -0.051 to 0.056
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Core Phase: Lemborexant-matched Placebo, Core Phase: Lemborexant 15 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0364
	Comments	Based on a MMRM analysis adjusted for baseline value, country, visit and treatment by visit interaction
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	0.057
	Confidence Interval	(2-Sided) 95% 0.004 to 0.110
	Parameter Dispersion	Type: Value:
	Estimation Comments

49. Other Pre-specified Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Description
Time Frame	First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg	Extension Phase: Lemborexant 5 mg	Extension Phase: Lemborexant 10 mg	Extension Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12	5	14	6
TEAEs	4 33.3%	3 25%	3 23.1%	4 30.8%	6 50%	4 6.5%	10 NaN	5 NaN
SAEs	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.6%	2 NaN	1 NaN

50. Other Pre-specified Outcome

Title	Core Phase: Number of Participants in Each Category With Clinician's Global Impression of Change-Irregular Sleep-Wake Rhythm Disorder (CGIC-ISWRD) Global Score at Day 29
Description	The CGIC-ISWRD scale is a validated categorical measure of change in the participant's clinical condition between baseline and follow-up visits. It relies on both direct examination of the participant and an interview of the informant. The instrument consisted of 3 parts: a guided baseline interview administered to the participant and an informant, a follow-up interview administered to the participant and an informant, and a clinician's rating review. The baseline interview served as a reference for future ratings. During the baseline interview, the rater evaluated participant regarding domains of (1) sleep and wake symptoms; (2) mood and behavioral symptoms; (3) attention/arousal; and (4) social functioning. In the follow-up interview, a 7-pointscale was used, from 1 = marked improvement, 4 = no change, to 7 = marked worsening, to score each of the 4 domains and to provide a global score (1 [marked improvement] to 7 [marked worsening]).
Time Frame	Day 29

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Global score: Marked improvement	1 8.3%	0 0%	0 0%	0 0%	0 0%
Global score: Moderate improvement	1 8.3%	0 0%	2 15.4%	1 7.7%	0 0%
Global score: Minimal improvement	4 33.3%	4 33.3%	4 30.8%	5 38.5%	3 25%
Global score: No change	6 50%	5 41.7%	4 30.8%	3 23.1%	7 58.3%
Global score: Minimal worsening	0 0%	3 25%	2 15.4%	3 23.1%	1 8.3%
Global score : Moderate worsening	0 0%	0 0%	0 0%	0 0%	0 0%
Global score : Marked worsening	0 0%	0 0%	0 0%	0 0%	0 0%

51. Other Pre-specified Outcome

Title	Core Phase: Change From Baseline in the Neuropsychiatric Inventory (NPI-10) Total Score at Day 29
Description	The NPI-10 assessed a wide range of behaviors seen in dementia for both frequency and severity. It is a 10 item questionnaire with the following domains: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/liability and aberrant motor behavior. The total score was summarized and analyzed. This scale was administered with the caregiver as proxy for the participant. The total score was a sum of the 10 domains, where the score of each domain was calculated as frequency (scale: 1=occasionally to 4=very frequently) * Severity (scale: 1=Mild to 3=Severe). Each domain has a maximum score of 12 and all domains were equally weighted for total score, thus the range for the total score is 0 to 120 with 0 being completely healthy to 120 which is the worse score participant could get.
Time Frame	Baseline, Day 29

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	12
Baseline	3.8 (4.13)	13.1 (17.77)	7.7 (12.32)	6.4 (10.27)	5.5 (5.73)
Change at Day 29	-2.8 (3.64)	-3.4 (9.23)	-0.3 (5.85)	-3.4 (8.95)	3.8 (13.02)

52. Other Pre-specified Outcome

Title	Core Phase: Change From Baseline in the Sleep Disorders Inventory (SDI) Score at Day 29
Description	The SDI is an expanded version of one item of the NPI. It described the frequency, severity, and caregiver burden of sleep-disturbed behaviors during a period prior to its administration. The SDI consists of the 7 sub questions relating to sleep from the NPI sleep disturbance item. Each of the sub questions is a separate question with frequency, severity, and caregiver distress rated by the caregiver with respect to the patient-participant for the 2 weeks prior to the visit. The SDI score is derived as the product of the average of the frequency ratings and the average of the severity ratings (range: 0-12 [worst]).
Time Frame	Baseline, Day 29

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Core Phase: Lemborexant-matched Placebo	Core Phase: Lemborexant 2.5 mg	Core Phase: Lemborexant 5 mg	Core Phase: Lemborexant 10 mg	Core Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	12	12	13	13	11
Baseline	0.79 (0.692)	1.24 (1.576)	0.74 (0.653)	0.66 (0.748)	1.44 (1.708)
Change at Day 29	-0.48 (1.078)	-0.10 (0.616)	-0.33 (0.503)	-0.09 (0.574)	-0.49 (1.220)

53. Other Pre-specified Outcome

Title	Extension Phase: Change From Baseline in SDI Total Score.
Description	The SDI is an expanded version of one item of the NPI. It described the frequency, severity, and caregiver burden of sleep-disturbed behaviors during a period prior to its administration. The SDI consists of the 7 sub questions relating to sleep from the NPI sleep disturbance item. Each of the sub questions is a separate question with frequency, severity, and caregiver distress rated by the caregiver with respect to the patient-participant for the 2 weeks prior to the visit. The SDI score is derived as the product of the average of the frequency ratings and the average of the severity ratings (range: 0-12 [worst]).
Time Frame	Baseline, Day 133, 223, 313, 343, 373, 403, 493, 583, 673, and 763

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Extension Phase: Lemborexant 5 mg	Extension Phase: Lemborexant 10 mg	Extension Phase: Lemborexant 15 mg
Arm/Group Description	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.	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.	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.
Measure Participants	5	12	6
Baseline	1.36 (1.948)	0.74 (0.728)	1.45 (2.331)
Change at Day 133 (Visit 9)	1.40	-0.45 (0.600)	-0.63 (0.473)
Change at Day 223 (Visit 12)	-0.60 (0.693)	0.17 (0.306)
Change at Day 313 (Visit 15)	-0.65 (0.574)	-0.17 (1.266)
Change at Day 343 (Visit 16)	0.60	0.55 (1.061)	0.45 (0.919)
Change at Day 373 (Visit 17)	-0.20
Change at Day 403 (Visit 18)	-0.50 (0.539)	-0.55 (0.656)
Change at Day 493 (Visit 19)	-0.13 (0.115)	-0.10
Change at Day 583 (Visit 20)	-0.15 (0.071)	-0.35 (0.354)
Change at Day 673 (Visit 21)	-0.30	-0.15 (0.071)
Change at Day 763 (Visit 22)	-0.05 (0.354)

Adverse Events

	Core Phase: Lemborexant-matched Placebo		Core Phase: Lemborexant 2.5 mg		Core Phase: Lemborexant 5 mg		Core Phase: Lemborexant 10 mg		Core Phase: Lemborexant 15 mg		Extension Phase: Lemborexant 5 mg		Extension Phase: Lemborexant 10 mg		Extension Phase: Lemborexant 15 mg
Time Frame	First dose of study drug (Day 1) to 14 days after last dose of study drug (approximately up to 2 years 7 months)
Adverse Event Reporting Description

Arm/Group Title	Core Phase: Lemborexant-matched Placebo		Core Phase: Lemborexant 2.5 mg		Core Phase: Lemborexant 5 mg		Core Phase: Lemborexant 10 mg		Core Phase: Lemborexant 15 mg		Extension Phase: Lemborexant 5 mg		Extension Phase: Lemborexant 10 mg		Extension Phase: Lemborexant 15 mg
Arm/Group Description	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.		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.		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.		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.		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.		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.		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.		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.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/13 (0%)		0/12 (0%)		0/5 (0%)		0/14 (0%)		0/6 (0%)
Serious Adverse Events
	Core Phase: Lemborexant-matched Placebo		Core Phase: Lemborexant 2.5 mg		Core Phase: Lemborexant 5 mg		Core Phase: Lemborexant 10 mg		Core Phase: Lemborexant 15 mg		Extension Phase: Lemborexant 5 mg		Extension Phase: Lemborexant 10 mg		Extension Phase: Lemborexant 15 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)		0/13 (0%)		0/13 (0%)		0/12 (0%)		1/5 (20%)		2/14 (14.3%)		1/6 (16.7%)
General disorders
Asthenia	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	0/5 (0%)	0	1/14 (7.1%)	1	0/6 (0%)	0
Injury, poisoning and procedural complications
Ilium fracture	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	0/5 (0%)	0	0/14 (0%)	0	1/6 (16.7%)	1
Nervous system disorders
Ischaemic stroke	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	1/5 (20%)	1	0/14 (0%)	0	0/6 (0%)	0
Respiratory, thoracic and mediastinal disorders
Hypercapnia	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	0/5 (0%)	0	1/14 (7.1%)	1	0/6 (0%)	0
Hypoxia	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	0/5 (0%)	0	1/14 (7.1%)	1	0/6 (0%)	0
Vascular disorders
Orthostatic hypotension	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	0/5 (0%)	0	1/14 (7.1%)	1	0/6 (0%)	0
Other (Not Including Serious) Adverse Events
	Core Phase: Lemborexant-matched Placebo		Core Phase: Lemborexant 2.5 mg		Core Phase: Lemborexant 5 mg		Core Phase: Lemborexant 10 mg		Core Phase: Lemborexant 15 mg		Extension Phase: Lemborexant 5 mg		Extension Phase: Lemborexant 10 mg		Extension Phase: Lemborexant 15 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/12 (33.3%)		3/12 (25%)		3/13 (23.1%)		4/13 (30.8%)		6/12 (50%)		4/5 (80%)		10/14 (71.4%)		5/6 (83.3%)
Blood and lymphatic system disorders
Nephrogenic anaemia	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	0/5 (0%)	0	1/14 (7.1%)	1	0/6 (0%)	0
Cardiac disorders
Atrioventricular block first degree	0/12 (0%)	0	0/12 (0%)	0	1/13 (7.7%)	1	0/13 (0%)	0	0/12 (0%)	0	0/5 (0%)	0	1/14 (7.1%)	1	0/6 (0%)	0
Bradycardia	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	1/12 (8.3%)	1	1/5 (20%)	1	0/14 (0%)	0	0/6 (0%)	0
Palpitations	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	1/12 (8.3%)	1	0/5 (0%)	0	0/14 (0%)	0	0/6 (0%)	0
Gastrointestinal disorders
Constipation	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	1/13 (7.7%)	1	2/12 (16.7%)	2	0/5 (0%)	0	0/14 (0%)	0	1/6 (16.7%)	1
Diarrhoea	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	1/12 (8.3%)	1	1/5 (20%)	1	0/14 (0%)	0	2/6 (33.3%)	2
Dry mouth	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	1/12 (8.3%)	1	0/5 (0%)	0	0/14 (0%)	0	1/6 (16.7%)	1
Intestinal obstruction	0/12 (0%)	0	1/12 (8.3%)	1	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	0/5 (0%)	0	0/14 (0%)	0	0/6 (0%)	0
Diverticulum	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	0/5 (0%)	0	1/14 (7.1%)	1	0/6 (0%)	0
Dyspepsia	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	0/5 (0%)	0	1/14 (7.1%)	1	0/6 (0%)	0
Infections and infestations
Bronchitis	0/12 (0%)	0	0/12 (0%)	0	1/13 (7.7%)	1	0/13 (0%)	0	0/12 (0%)	0	0/5 (0%)	0	0/14 (0%)	0	0/6 (0%)	0
Cellulitis	0/12 (0%)	0	1/12 (8.3%)	1	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	0/5 (0%)	0	1/14 (7.1%)	1	0/6 (0%)	0
Eye infection	1/12 (8.3%)	1	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	0/5 (0%)	0	0/14 (0%)	0	0/6 (0%)	0
Nasopharyngitis	1/12 (8.3%)	1	0/12 (0%)	0	1/13 (7.7%)	1	0/13 (0%)	0	0/12 (0%)	0	0/5 (0%)	0	4/14 (28.6%)	4	2/6 (33.3%)	2
Urinary tract infection	1/12 (8.3%)	1	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	0/5 (0%)	0	0/14 (0%)	0	1/6 (16.7%)	1
Cystitis	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	0/5 (0%)	0	0/14 (0%)	0	1/6 (16.7%)	1
Otitis media	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	0/5 (0%)	0	1/14 (7.1%)	1	0/6 (0%)	0
Tooth abscess	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	0/5 (0%)	0	0/14 (0%)	0	1/6 (16.7%)	1
Upper respiratory tract infection	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	0/5 (0%)	0	2/14 (14.3%)	2	0/6 (0%)	0
Injury, poisoning and procedural complications
Contusion	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	1/5 (20%)	1	0/14 (0%)	0	0/6 (0%)	0
Fall	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	1/5 (20%)	1	2/14 (14.3%)	2	1/6 (16.7%)	1
Genital injury	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	0/5 (0%)	0	1/14 (7.1%)	1	0/6 (0%)	0
Joint injury	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	0/5 (0%)	0	1/14 (7.1%)	1	0/6 (0%)	0
Laceration	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	0/5 (0%)	0	1/14 (7.1%)	1	0/6 (0%)	0
Limb injury	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	0/5 (0%)	0	1/14 (7.1%)	1	0/6 (0%)	0
Upper limb fracture	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	1/5 (20%)	1	0/14 (0%)	0	0/6 (0%)	0
Metabolism and nutrition disorders
Hypercholesterolaemia	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	0/5 (0%)	0	0/14 (0%)	0	1/6 (16.7%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	2/12 (16.7%)	3	0/5 (0%)	0	0/14 (0%)	0	1/6 (16.7%)	1
Musculoskeletal pain	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	1/12 (8.3%)	1	0/5 (0%)	0	0/14 (0%)	0	0/6 (0%)	0
Osteoporosis	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	1/5 (20%)	1	0/14 (0%)	0	0/6 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of skin	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	0/5 (0%)	0	1/14 (7.1%)	1	0/6 (0%)	0
Nervous system disorders
Dizziness	0/12 (0%)	0	1/12 (8.3%)	1	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	0/5 (0%)	0	1/14 (7.1%)	1	0/6 (0%)	0
Headache	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	2/12 (16.7%)	2	0/5 (0%)	0	0/14 (0%)	0	1/6 (16.7%)	1
Sedation	0/12 (0%)	0	0/12 (0%)	0	1/13 (7.7%)	1	0/13 (0%)	0	0/12 (0%)	0	1/5 (20%)	1	0/14 (0%)	0	0/6 (0%)	0
Somnolence	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	1/13 (7.7%)	1	2/12 (16.7%)	2	3/5 (60%)	3	0/14 (0%)	0	0/6 (0%)	0
Syncope	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	0/5 (0%)	0	0/14 (0%)	0	1/6 (16.7%)	1
Psychiatric disorders
Libido increased	0/12 (0%)	0	0/12 (0%)	0	1/13 (7.7%)	1	0/13 (0%)	0	0/12 (0%)	0	0/5 (0%)	0	0/14 (0%)	0	0/6 (0%)	0
Nightmare	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	2/13 (15.4%)	2	0/12 (0%)	0	0/5 (0%)	0	1/14 (7.1%)	1	0/6 (0%)	0
Anxiety	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	0/5 (0%)	0	1/14 (7.1%)	1	0/6 (0%)	0
Delirium	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	1/5 (20%)	1	0/14 (0%)	0	0/6 (0%)	0
Depression	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	0/5 (0%)	0	3/14 (21.4%)	3	0/6 (0%)	0
Irritability	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	1/5 (20%)	1	0/14 (0%)	0	0/6 (0%)	0
Renal and urinary disorders
Nephrolithiasis	1/12 (8.3%)	1	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	0/5 (0%)	0	0/14 (0%)	0	0/6 (0%)	0
Acute kidney injury	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	1/5 (20%)	1	0/14 (0%)	0	0/6 (0%)	0
Chronic kidney disease	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	0/5 (0%)	0	1/14 (7.1%)	1	0/6 (0%)	0
Reproductive system and breast disorders
Genital discharge	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	0/12 (0%)	0	0/5 (0%)	0	1/14 (7.1%)	1	0/6 (0%)	0
Vascular disorders
Hypertension	0/12 (0%)	0	0/12 (0%)	0	0/13 (0%)	0	0/13 (0%)	0	1/12 (8.3%)	1	0/5 (0%)	0	0/14 (0%)	0	0/6 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title	Eisai Medical Information
Organization	Eisai Inc.
Phone	1-888-274-2378
Email	esi_medinfo@eisai.com

Responsible Party:

Eisai Inc.

ClinicalTrials.gov Identifier:

NCT03001557

Other Study ID Numbers:

E2006-G000-202
2017-003306-40

First Posted:

Dec 23, 2016

Last Update Posted:

May 17, 2021

Last Verified:

Apr 1, 2021