Trial Outcomes & Findings for A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Bayesian Adaptive Randomization Design, Dose Response Study of the Efficacy of E2006 in Adults and Elderly Subjects With Chronic Insomnia (NCT NCT01995838)

NCT ID: NCT01995838

Last Updated: 2020-01-31

Results Overview

The utility of a dose was a function of both Sleep Efficiency (SE) and Karolinska Sleepiness Scale (KSS), constructed by specifying the 1-dimensional component for each outcome measure and then combining them multiplicatively. Sufficient utility was defined as a probability of having utility function \>1. Probability of having utility function \>1 at the end of study visit (full analysis) was reported.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

291 participants

Primary outcome timeframe

Baseline up to Day 3

Results posted on

2020-01-31

Participant Flow

Participants took part in the study at 23 investigative sites in the United States from 13 Nov 2013 to 29 Apr 2014.

A total of 616 participants were screened, of which 325 were screen failures and 291 were randomized to receive study treatment.

Participant milestones

Participant milestones
Measure	Placebo Participants received lemborexant placebo-matching tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 1 Milligram (mg) Participants received lemborexant 1 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 2.5 mg Participants received lemborexant 2.5 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 5 mg Participants received lemborexant 5 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 10 mg Participants received lemborexant 10 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 15 mg Participants received lemborexant 15 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 25 mg Participants received lemborexant 25 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.
Overall Study STARTED	56	32	27	38	32	56	50
Overall Study COMPLETED	51	30	27	36	30	54	45
Overall Study NOT COMPLETED	5	2	0	2	2	2	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received lemborexant placebo-matching tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 1 Milligram (mg) Participants received lemborexant 1 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 5 mg Participants received lemborexant 5 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 10 mg Participants received lemborexant 10 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 15 mg Participants received lemborexant 15 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 25 mg Participants received lemborexant 25 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.
Overall Study Lost to Follow-up	0	1	0	0	0	1
Overall Study Participant choice	2	0	0	0	1	1
Overall Study Adverse Event	0	0	0	0	0	1
Overall Study Withdrawal by Subject	0	0	0	1	0	0
Overall Study Other	3	1	2	1	1	2

Baseline Characteristics

A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Bayesian Adaptive Randomization Design, Dose Response Study of the Efficacy of E2006 in Adults and Elderly Subjects With Chronic Insomnia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lemborexant 1 mg n=32 Participants Participants received lemborexant 1 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 2.5 mg n=27 Participants Participants received lemborexant 2.5 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 5 mg n=38 Participants Participants received lemborexant 5 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 10 mg n=32 Participants Participants received lemborexant 10 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 15 mg n=56 Participants Participants received lemborexant 15 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 25 mg n=50 Participants Participants received lemborexant 25 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Placebo n=56 Participants Participants received lemborexant placebo-matching tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Total n=291 Participants Total of all reporting groups
Age, Continuous	53.3 Years STANDARD_DEVIATION 13.0 • n=5 Participants	49.7 Years STANDARD_DEVIATION 14.3 • n=7 Participants	51.1 Years STANDARD_DEVIATION 14.3 • n=5 Participants	47.1 Years STANDARD_DEVIATION 13.7 • n=4 Participants	44.0 Years STANDARD_DEVIATION 14.6 • n=21 Participants	48.9 Years STANDARD_DEVIATION 13.4 • n=8 Participants	47.1 Years STANDARD_DEVIATION 15.6 • n=8 Participants	48.3 Years STANDARD_DEVIATION 14.4 • n=24 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	17 Participants n=7 Participants	23 Participants n=5 Participants	20 Participants n=4 Participants	32 Participants n=21 Participants	31 Participants n=8 Participants	36 Participants n=8 Participants	182 Participants n=24 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	10 Participants n=7 Participants	15 Participants n=5 Participants	12 Participants n=4 Participants	24 Participants n=21 Participants	19 Participants n=8 Participants	20 Participants n=8 Participants	109 Participants n=24 Participants

PRIMARY outcome

Timeframe: Baseline up to Day 3

Population: The full analysis set (FAS) included all participants who were randomized, received at least 1 dose of study drug and had at least 1 postdose primary efficacy measurement.

Outcome measures

Outcome measures
Measure	Lemborexant 15 mg n=56 Participants Participants received lemborexant 15 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 1 mg n=32 Participants Participants received lemborexant 1 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 2.5 mg n=27 Participants Participants received lemborexant 2.5 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 5 mg n=38 Participants Participants received lemborexant 5 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 10 mg n=32 Participants Participants received lemborexant 10 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 25 mg n=50 Participants Participants received lemborexant 25 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Placebo Participants received lemborexant placebo-matching tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.
Probability of Having Utility Function Greater Than (>) 1 Based on Bayesian Analysis	0.9866 probability	0.8789 probability	0.8920 probability	0.9032 probability	0.9406 probability	0.9675 probability	—

PRIMARY outcome

Timeframe: 1 hour after morning wake time at Baseline and Days 15-16

Population: The FAS included all participants who were randomized, received at least 1 dose of study drug and had at least 1 post-dose primary efficacy measurement. Here, number of participants analyzed (N) represents participants who were available for analysis at the specified timepoints.

The KSS was used to measure next-day residual effects at prespecified time points. The KSS was a 9-point scale on which the participant rated their sleepiness from 1 (extremely alert) to 9 (extremely sleepy/fighting sleep), where higher scores indicated an increase in sleepiness. The end of treatment score was calculated by the mean scores at the timepoint at 1 hour after morning wake time of Day 15 and 16.

Outcome measures

Outcome measures
Measure	Lemborexant 15 mg n=54 Participants Participants received lemborexant 15 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 1 mg n=31 Participants Participants received lemborexant 1 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 2.5 mg n=27 Participants Participants received lemborexant 2.5 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 5 mg n=37 Participants Participants received lemborexant 5 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 10 mg n=31 Participants Participants received lemborexant 10 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 25 mg n=46 Participants Participants received lemborexant 25 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Placebo n=51 Participants Participants received lemborexant placebo-matching tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.
Mean Change From Baseline in Karolinska Sleepiness Scale (KSS) Score at End of Treatment	0.16 Units on a scale Standard Error 0.166	0.29 Units on a scale Standard Error 0.219	-0.10 Units on a scale Standard Error 0.234	0.20 Units on a scale Standard Error 0.200	-0.22 Units on a scale Standard Error 0.219	0.45 Units on a scale Standard Error 0.180	-0.23 Units on a scale Standard Error 0.170

SECONDARY outcome

Timeframe: Baseline, Days 1-2, and Days 14-15

Population: The FAS included all participants who were randomized, received at least 1 dose of study drug, had at least 1 post-dose primary efficacy measurement with both baseline and post baseline data available for analysis at each timepoints.

Sleep efficiency was calculated as total sleep time divided by time spent in bed multiplied by 100. An increase in SE indicated improvement in sleeping, such that, the participant spends more time in bed asleep. Mean scores of Days 1-2 and Days 14-15 were used to evaluate change from baseline.

Outcome measures

Outcome measures
Measure	Lemborexant 15 mg n=56 Participants Participants received lemborexant 15 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 1 mg n=32 Participants Participants received lemborexant 1 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 2.5 mg n=27 Participants Participants received lemborexant 2.5 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 5 mg n=38 Participants Participants received lemborexant 5 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 10 mg n=32 Participants Participants received lemborexant 10 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 25 mg n=50 Participants Participants received lemborexant 25 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Placebo n=56 Participants Participants received lemborexant placebo-matching tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.
Mean Change From Baseline in Sleep Efficiency (SE) After Dosing on Days 1-2 and Days 14-15 Days 1-2	24.22 percentage of sleep time Standard Error 1.029	18.72 percentage of sleep time Standard Error 1.366	18.59 percentage of sleep time Standard Error 1.487	19.89 percentage of sleep time Standard Error 1.250	22.25 percentage of sleep time Standard Error 1.361	24.28 percentage of sleep time Standard Error 1.091	14.16 percentage of sleep time Standard Error 1.031
Mean Change From Baseline in Sleep Efficiency (SE) After Dosing on Days 1-2 and Days 14-15 Days 14-15	21.97 percentage of sleep time Standard Error 1.077	14.43 percentage of sleep time Standard Error 1.428	18.02 percentage of sleep time Standard Error 1.528	19.85 percentage of sleep time Standard Error 1.302	21.87 percentage of sleep time Standard Error 1.421	22.96 percentage of sleep time Standard Error 1.169	14.08 percentage of sleep time Standard Error 1.100

SECONDARY outcome

Timeframe: Baseline, Days 1-2, and Days 14-15

LPS was calculated as minutes from lights off to the first 30-second epoch of 20 consecutive epochs of non-wakefulness. A decrease in LPS indicated improvement in time needed to fall asleep. Mean scores of Days 1-2 and Days 14-15 were used to evaluate change from baseline.

Outcome measures

Outcome measures
Measure	Lemborexant 15 mg n=56 Participants Participants received lemborexant 15 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 1 mg n=32 Participants Participants received lemborexant 1 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 2.5 mg n=27 Participants Participants received lemborexant 2.5 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 5 mg n=38 Participants Participants received lemborexant 5 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 10 mg n=32 Participants Participants received lemborexant 10 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 25 mg n=50 Participants Participants received lemborexant 25 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Placebo n=56 Participants Participants received lemborexant placebo-matching tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.
Mean Change From Baseline in Latency to Persistent Sleep (LPS) After Dosing on Days 1-2 and Days 14-15 Days 1-2	-51.59 minutes Standard Deviation 36.728	-42.92 minutes Standard Deviation 41.855	-52.74 minutes Standard Deviation 50.149	-47.72 minutes Standard Deviation 39.389	-46.80 minutes Standard Deviation 46.106	-50.16 minutes Standard Deviation 43.140	-22.90 minutes Standard Deviation 44.457
Mean Change From Baseline in Latency to Persistent Sleep (LPS) After Dosing on Days 1-2 and Days 14-15 Days 14-15	-51.95 minutes Standard Deviation 41.926	-41.23 minutes Standard Deviation 34.618	-54.24 minutes Standard Deviation 44.918	-51.86 minutes Standard Deviation 41.994	-56.14 minutes Standard Deviation 45.553	-50.79 minutes Standard Deviation 40.160	-22.43 minutes Standard Deviation 29.045

SECONDARY outcome

Timeframe: Baseline, Days 1-2, and Days 14-15

WASO was calculated as minutes of wakefulness from the onset of persistent sleep until lights on. A decrease in WASO indicated improvement in sleep maintenance. Mean scores of Days 1-2 and Days 14-15 were used to evaluate change from baseline.

Outcome measures

Outcome measures
Measure	Lemborexant 15 mg n=56 Participants Participants received lemborexant 15 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 1 mg n=32 Participants Participants received lemborexant 1 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 2.5 mg n=27 Participants Participants received lemborexant 2.5 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 5 mg n=38 Participants Participants received lemborexant 5 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 10 mg n=32 Participants Participants received lemborexant 10 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 25 mg n=50 Participants Participants received lemborexant 25 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Placebo n=56 Participants Participants received lemborexant placebo-matching tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.
Mean Change From Baseline in Wakefulness After Sleep Onset (WASO) After Dosing on Days 1-2 and Days 14-15 Days 1-2	-70.38 minutes Standard Error 4.103	-52.11 minutes Standard Error 5.441	-43.33 minutes Standard Error 5.915	-52.29 minutes Standard Error 5.423	-60.84 minutes Standard Error 1.302	-66.87 minutes Standard Error 4.342	-41.03 minutes Standard Error 4.095
Mean Change From Baseline in Wakefulness After Sleep Onset (WASO) After Dosing on Days 1-2 and Days 14-15 Days 14-15	-58.95 minutes Standard Error 4.651	-32.46 minutes Standard Error 6.159	-40.47 minutes Standard Error 6.581	-48.84 minutes Standard Error 5.609	-52.88 minutes Standard Error 6.129	-59.67 minutes Standard Error 5.039	-38.15 minutes Standard Error 4.728

SECONDARY outcome

Timeframe: Baseline, Days 1-2, and Days 14-15

Population: The FAS included all participants who were randomized, received at least 1 dose of study drug and had at least 1 post-dose primary efficacy measurement. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.

Potential habituation effect evaluated the possibility of participants being habituated to changes in sleep during the 15 days of treatment with lemborexant. Data reported here was calculated as change from baseline of mean SE of Days 14-15 minus change from baseline of mean SE of Days 1-2. An increase in SE indicated improvement in sleeping, such that, the participant spends more time in bed asleep.

Outcome measures

Outcome measures
Measure	Lemborexant 15 mg n=54 Participants Participants received lemborexant 15 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 1 mg n=31 Participants Participants received lemborexant 1 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 2.5 mg n=27 Participants Participants received lemborexant 2.5 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 5 mg n=37 Participants Participants received lemborexant 5 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 10 mg n=31 Participants Participants received lemborexant 10 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 25 mg n=46 Participants Participants received lemborexant 25 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Placebo n=52 Participants Participants received lemborexant placebo-matching tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.
Potential Habituation Effect: Comparison Between Mean Change From Baseline in SE on Days 1-2 and Mean Change From Baseline in SE on Days 14-15	-2.33 percentage of sleep time Standard Deviation 6.600	-4.04 percentage of sleep time Standard Deviation 8.194	-0.54 percentage of sleep time Standard Deviation 10.505	0.06 percentage of sleep time Standard Deviation 6.888	-0.68 percentage of sleep time Standard Deviation 6.883	-2.15 percentage of sleep time Standard Deviation 5.388	-1.05 percentage of sleep time Standard Deviation 7.192

SECONDARY outcome

Timeframe: Baseline and Days 1-2, and Days 14-15

Potential habituation effect evaluated the possibility of participants being habituated to changes in sleep during the 15 days of treatment with lemborexant. Data reported here was calculated as change from baseline of mean LPS of Days 14-15 minus change from baseline of mean LPS of Days 1-2. LPS was calculated as minutes from lights off to the first 30-second epoch of 20 consecutive epochs of non-wakefulness. A decrease in LPS indicated improvement in time needed to fall asleep.

Outcome measures

Outcome measures
Measure	Lemborexant 15 mg n=54 Participants Participants received lemborexant 15 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 1 mg n=31 Participants Participants received lemborexant 1 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 2.5 mg n=27 Participants Participants received lemborexant 2.5 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 5 mg n=37 Participants Participants received lemborexant 5 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 10 mg n=31 Participants Participants received lemborexant 10 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 25 mg n=46 Participants Participants received lemborexant 25 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Placebo n=52 Participants Participants received lemborexant placebo-matching tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.
Potential Habituation Effect: Comparison Between Mean Change From Baseline in Latency to Persistent Sleep (LPS) on Days 1-2 and Mean Change From Baseline in LPS on Days 14-15	-1.11 minutes Standard Deviation 24.568	2.71 minutes Standard Deviation 24.333	-1.50 minutes Standard Deviation 22.120	-4.60 minutes Standard Deviation 22.337	-7.93 minutes Standard Deviation 17.415	1.38 minutes Standard Deviation 12.046	0.57 minutes Standard Deviation 40.855

SECONDARY outcome

Timeframe: Baseline, Days 1-2, and Days 14-15

Potential habituation effect evaluated the possibility of participants being habituated to changes in sleep during the 15 days of treatment with lemborexant. Data reported here was calculated as change from baseline of mean WASO of Days 14-15 minus change from baseline of mean WASO of Days 1-2. WASO was calculated as minutes of wakefulness from the onset of persistent sleep until lights on. A decrease in WASO indicated improvement in sleep maintenance.

Outcome measures

Outcome measures
Measure	Lemborexant 15 mg n=54 Participants Participants received lemborexant 15 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 1 mg n=31 Participants Participants received lemborexant 1 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 2.5 mg n=27 Participants Participants received lemborexant 2.5 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 5 mg n=36 Participants Participants received lemborexant 5 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 10 mg n=31 Participants Participants received lemborexant 10 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 25 mg n=45 Participants Participants received lemborexant 25 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Placebo n=52 Participants Participants received lemborexant placebo-matching tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.
Potential Habituation Effect: Comparison Between Mean Change From Baseline in Wakefulness After Sleep Onset (WASO) on Days 1-2 and Mean Change From Baseline in WASO on Days 14-15	11.76 minutes Standard Deviation 26.187	17.98 minutes Standard Deviation 34.299	2.16 minutes Standard Deviation 44.054	2.68 minutes Standard Deviation 29.726	9.30 minutes Standard Deviation 25.890	9.28 minutes Standard Deviation 23.119	5.99 minutes Standard Deviation 31.417

SECONDARY outcome

Timeframe: Baseline and Days 16-17

Rebound insomnia was assessed by comparing the change from baseline of the mean SE on Days 16-17. Sleep efficiency was calculated as total sleep time divided by time spent in bed multiplied by 100. An increase in SE indicated improvement in sleeping, such that, the participant spends more time in bed asleep. A negative change from baseline in SE indicated that SE was worse on Days 16 and 17 than at Baseline, which was considered as evidence for rebound insomnia.

Outcome measures

Outcome measures
Measure	Lemborexant 15 mg n=54 Participants Participants received lemborexant 15 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 1 mg n=31 Participants Participants received lemborexant 1 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 2.5 mg n=27 Participants Participants received lemborexant 2.5 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 5 mg n=36 Participants Participants received lemborexant 5 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 10 mg n=31 Participants Participants received lemborexant 10 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 25 mg n=45 Participants Participants received lemborexant 25 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Placebo n=52 Participants Participants received lemborexant placebo-matching tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.
Rebound Insomnia: Mean Change From Baseline in Sleep Efficiency (SE) After Dosing on Days 16-17	18.58 percentage of sleep time Standard Error 1.253	13.12 percentage of sleep time Standard Error 1.661	15.53 percentage of sleep time Standard Error 1.777	17.67 percentage of sleep time Standard Error 1.535	13.78 percentage of sleep time Standard Error 1.653	17.12 percentage of sleep time Standard Error 1.374	16.17 percentage of sleep time Standard Error 1.280

SECONDARY outcome

Timeframe: TEAEs: Baseline up to Day 30, SAEs: Baseline up to 30 days after last dose of study drug (up to 47 days)

Population: The safety analysis set included all participants who received at least 1 dose of study drug and had at least 1 post-dose safety assessment.

Outcome measures

Outcome measures
Measure	Lemborexant 15 mg n=56 Participants Participants received lemborexant 15 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 1 mg n=32 Participants Participants received lemborexant 1 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 2.5 mg n=27 Participants Participants received lemborexant 2.5 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 5 mg n=38 Participants Participants received lemborexant 5 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 10 mg n=32 Participants Participants received lemborexant 10 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 25 mg n=50 Participants Participants received lemborexant 25 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Placebo n=56 Participants Participants received lemborexant placebo-matching tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.
Percentage of Participants With Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) TEAE	55.4 percentage of participants	34.4 percentage of participants	40.7 percentage of participants	42.1 percentage of participants	59.4 percentage of participants	60.0 percentage of participants	37.5 percentage of participants
Percentage of Participants With Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) SAE	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	2.0 percentage of participants	1.8 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to Day 30

Population: The safety analysis set included all participants who received at least 1 dose of study drug and had at least 1 post-dose safety assessment.

Outcome measures

Outcome measures
Measure	Lemborexant 15 mg n=56 Participants Participants received lemborexant 15 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 1 mg n=32 Participants Participants received lemborexant 1 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 2.5 mg n=27 Participants Participants received lemborexant 2.5 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 5 mg n=38 Participants Participants received lemborexant 5 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 10 mg n=32 Participants Participants received lemborexant 10 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 25 mg n=50 Participants Participants received lemborexant 25 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Placebo n=56 Participants Participants received lemborexant placebo-matching tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.
Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Parameters	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline up to Day 30

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

Outcome measures

Outcome measures
Measure	Lemborexant 15 mg n=56 Participants Participants received lemborexant 15 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 1 mg n=32 Participants Participants received lemborexant 1 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 2.5 mg n=27 Participants Participants received lemborexant 2.5 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 5 mg n=38 Participants Participants received lemborexant 5 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 10 mg n=32 Participants Participants received lemborexant 10 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Lemborexant 25 mg n=50 Participants Participants received lemborexant 25 mg tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.	Placebo n=56 Participants Participants received lemborexant placebo-matching tablets, orally, once daily on Day 1 to Day 15 in the double-blind treatment phase, followed by lemborexant placebo-matching tablets, orally, once daily on Days 16 and 17 in the single-blind placebo run-out phase.
Number of Participants With Clinically Significant Change From Baseline in Vital Signs	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline up to Day 30

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