Trial Outcomes & Findings for Study to Evaluate the Effect of 2 Dosage Strengths of Lemborexant (E2006) on a Multiple Sleep Latency Test in Participants With Insomnia Disorder (NCT NCT02350309)

Last Updated: 2020-01-18

Results Overview

SOL is defined as the length of time that it takes to accomplish the transition from full wakefulness to sleep. The multiple sleep latency test (MSLT) is a widely used method for objectively quantifying excessive, pathological, or pharmacologically induced residual sleepiness by measuring the number of minutes that it takes a participant to fall asleep. The MSLT was modified to include four Sleep Latency Tests (SLTs), with the first starting at 45 minutes after morning wake time, and the subsequent three occurring at 30-minute intervals for a total of 4 SLT's per M-MSLT. Each SLT was scored to determine the latency in minutes (with precision to 0.5 minute) from lights off to sleep onset; trials during which sleep onset did not occur were assigned a latency of 20 minutes. The four SLTs for each participant were averaged to obtain the mean SOL.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

69 participants

Primary outcome timeframe

Baseline, Day 2 of each of three treatment periods that were separated by approximately 2 weeks (for a total of up to 4 weeks)

Results posted on

2020-01-18

Participant Flow

Participants took part in the study at 2 investigative sites in the United Sates from 13 December 2014 to 21 April 2015.

A total of 123 participants were screened, of which 54 participants were screen failures and 69 participants were randomized to receive study treatment.

Participant milestones

Participant milestones
Measure	Placebo, Lemborexant 5 mg, Lemborexant 10 mg, Flurazepam 30 mg Participants received a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Period 1, followed by a single oral dose of lemborexant 5 milligrams (mg) tablet, on Day 1 of Treatment Period 2, followed by a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Period 3, followed by a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4. All doses were administered within 5 minutes before bedtime. A washout period of 12 to 16 days was maintained between the 2 treatment periods.	Lemborexant 10 mg, Placebo, Lemborexant 5 mg, Flurazepam 30 mg Participants received a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Period 1, followed by a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Period 2, followed by a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Period 3, followed by a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4. All doses were administered within 5 minutes before bedtime. A washout period of 12 to 16 days was maintained between the 2 treatment periods.	Lemborexant 5 mg, Lemborexant 10 mg, Placebo, Flurazepam 30 mg Participants received a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Period 1, followed by a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Period 2, followed by a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Period 3, followed by a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4. All doses were administered within 5 minutes before bedtime. A washout period of 12 to 16 days was maintained between the 2 treatment periods.	Lemborexant 10 mg, Lemborexant 5 mg, Placebo, Flurazepam 30 mg Participants received a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Period 1, followed by a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Period 2, followed by a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Period 3, followed by a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4. All doses were administered within 5 minutes before bedtime. A washout period of 12 to 16 days was maintained between the 2 treatment periods.	Lemborexant 5 mg, Placebo, Lemborexant 10 mg, Flurazepam 30 mg Participants received a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Period 1, followed by a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Period 2, followed by a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Period 3, followed by a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4. All doses were administered within 5 minutes before bedtime. A washout period of 12 to 16 days was maintained between the 2 treatment periods.	Placebo, Lemborexant 10 mg, Lemborexant 5 mg, Flurazepam 30 mg Participants received a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Period 1, followed by a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Period 2, followed by a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Period 3, followed by a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4. All doses were administered within 5 minutes before bedtime. A washout period of 12 to 16 days was maintained between the 2 treatment periods.
Treatment Period 1 (2 Days) STARTED	12	11	11	11	12	12
Treatment Period 1 (2 Days) COMPLETED	12	11	10	11	12	12
Treatment Period 1 (2 Days) NOT COMPLETED	0	0	1	0	0	0
Washout Period 1 (12-16 Days) STARTED	12	11	10	11	12	12
Washout Period 1 (12-16 Days) COMPLETED	12	11	10	11	12	12
Washout Period 1 (12-16 Days) NOT COMPLETED	0	0	0	0	0	0
Treatment Period 2 (2 Days) STARTED	12	11	10	11	12	12
Treatment Period 2 (2 Days) COMPLETED	12	11	10	11	12	12
Treatment Period 2 (2 Days) NOT COMPLETED	0	0	0	0	0	0
Washout Period 2 (12-16 Days) STARTED	12	11	10	11	12	12
Washout Period 2 (12-16 Days) COMPLETED	12	11	10	11	12	12
Washout Period 2 (12-16 Days) NOT COMPLETED	0	0	0	0	0	0
Treatment Period 3 (2 Days) STARTED	12	11	10	11	12	12
Treatment Period 3 (2 Days) COMPLETED	12	11	10	11	12	12
Treatment Period 3 (2 Days) NOT COMPLETED	0	0	0	0	0	0
Washout Period 3 (12-16 Days) STARTED	12	11	10	11	12	12
Washout Period 3 (12-16 Days) COMPLETED	12	11	10	11	12	12
Washout Period 3 (12-16 Days) NOT COMPLETED	0	0	0	0	0	0
Treatment Period 4 (2 Days) STARTED	12	11	10	11	12	12
Treatment Period 4 (2 Days) COMPLETED	12	11	10	11	12	11
Treatment Period 4 (2 Days) NOT COMPLETED	0	0	0	0	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo, Lemborexant 5 mg, Lemborexant 10 mg, Flurazepam 30 mg Participants received a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Period 1, followed by a single oral dose of lemborexant 5 milligrams (mg) tablet, on Day 1 of Treatment Period 2, followed by a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Period 3, followed by a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4. All doses were administered within 5 minutes before bedtime. A washout period of 12 to 16 days was maintained between the 2 treatment periods.	Lemborexant 10 mg, Placebo, Lemborexant 5 mg, Flurazepam 30 mg Participants received a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Period 1, followed by a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Period 2, followed by a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Period 3, followed by a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4. All doses were administered within 5 minutes before bedtime. A washout period of 12 to 16 days was maintained between the 2 treatment periods.	Lemborexant 5 mg, Lemborexant 10 mg, Placebo, Flurazepam 30 mg Participants received a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Period 1, followed by a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Period 2, followed by a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Period 3, followed by a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4. All doses were administered within 5 minutes before bedtime. A washout period of 12 to 16 days was maintained between the 2 treatment periods.	Lemborexant 10 mg, Lemborexant 5 mg, Placebo, Flurazepam 30 mg Participants received a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Period 1, followed by a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Period 2, followed by a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Period 3, followed by a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4. All doses were administered within 5 minutes before bedtime. A washout period of 12 to 16 days was maintained between the 2 treatment periods.	Lemborexant 5 mg, Placebo, Lemborexant 10 mg, Flurazepam 30 mg Participants received a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Period 1, followed by a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Period 2, followed by a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Period 3, followed by a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4. All doses were administered within 5 minutes before bedtime. A washout period of 12 to 16 days was maintained between the 2 treatment periods.	Placebo, Lemborexant 10 mg, Lemborexant 5 mg, Flurazepam 30 mg Participants received a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Period 1, followed by a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Period 2, followed by a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Period 3, followed by a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4. All doses were administered within 5 minutes before bedtime. A washout period of 12 to 16 days was maintained between the 2 treatment periods.
Treatment Period 1 (2 Days) Physician Decision	0	0	1	0	0	0
Treatment Period 4 (2 Days) Death in the Family	0	0	0	0	0	1

Baseline Characteristics

Study to Evaluate the Effect of 2 Dosage Strengths of Lemborexant (E2006) on a Multiple Sleep Latency Test in Participants With Insomnia Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo, Lemborexant 5 mg, Lemborexant 10 mg, Flurazepam 30 mg n=12 Participants Participants received a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Period 1, followed by a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Period 2, followed by a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Period 3, followed by a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4. All doses were administered within 5 minutes before bedtime. A washout period of 12 to 16 days was maintained between the 2 treatment periods.	Lemborexant 10 mg, Placebo, Lemborexant 5 mg, Flurazepam 30 mg n=11 Participants Participants received a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Period 1, followed by a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Period 2, followed by a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Period 3, followed by a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4. All doses were administered within 5 minutes before bedtime. A washout period of 12 to 16 days was maintained between the 2 treatment periods.	Lemborexant 5 mg, Lemborexant 10 mg, Placebo, Flurazepam 30 mg n=11 Participants Participants received a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Period 1, followed by a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Period 2, followed by a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Period 3, followed by a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4. All doses were administered within 5 minutes before bedtime. A washout period of 12 to 16 days was maintained between the 2 treatment periods.	Lemborexant 10 mg, Lemborexant 5 mg, Placebo, Flurazepam 30 mg n=11 Participants Participants received a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Period 1, followed by a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Period 2, followed by a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Period 3, followed by a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4. All doses were administered within 5 minutes before bedtime. A washout period of 12 to 16 days was maintained between the 2 treatment periods.	Lemborexant 5 mg, Placebo, Lemborexant 10 mg, Flurazepam 30 mg n=12 Participants Participants received a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Period 1, followed by a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Period 2, followed by a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Period 3, followed by a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4. All doses were administered within 5 minutes before bedtime. A washout period of 12 to 16 days was maintained between the 2 treatment periods.	Placebo, Lemborexant 10 mg, Lemborexant 5 mg, Flurazepam 30 mg n=12 Participants Participants received a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Period 1, followed by a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Period 2, followed by a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Period 3, followed by a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4. All doses were administered within 5 minutes before bedtime. A washout period of 12 to 16 days was maintained between the 2 treatment periods.	Total n=69 Participants Total of all reporting groups
Age, Continuous	49.5 years STANDARD_DEVIATION 15.73 • n=5 Participants	50.2 years STANDARD_DEVIATION 12.54 • n=7 Participants	49.0 years STANDARD_DEVIATION 12.32 • n=5 Participants	52.5 years STANDARD_DEVIATION 15.91 • n=4 Participants	48.1 years STANDARD_DEVIATION 13.90 • n=21 Participants	52.2 years STANDARD_DEVIATION 7.86 • n=8 Participants	50.2 years STANDARD_DEVIATION 12.91 • n=8 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	8 Participants n=7 Participants	10 Participants n=5 Participants	9 Participants n=4 Participants	7 Participants n=21 Participants	8 Participants n=8 Participants	51 Participants n=8 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	5 Participants n=21 Participants	4 Participants n=8 Participants	18 Participants n=8 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=5 Participants	11 Participants n=7 Participants	11 Participants n=5 Participants	11 Participants n=4 Participants	12 Participants n=21 Participants	12 Participants n=8 Participants	69 Participants n=8 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=8 Participants	1 Participants n=8 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	7 Participants n=7 Participants	7 Participants n=5 Participants	3 Participants n=4 Participants	6 Participants n=21 Participants	5 Participants n=8 Participants	33 Participants n=8 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	8 Participants n=4 Participants	5 Participants n=21 Participants	7 Participants n=8 Participants	35 Participants n=8 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants

PRIMARY outcome

Timeframe: Baseline, Day 2 of each of three treatment periods that were separated by approximately 2 weeks (for a total of up to 4 weeks)

Population: The full analysis set (FAS) was the group of randomized participants who received at least 1 dose of study drug and had at least 1 postdose pharmacodynamics (PD) measurement.

Outcome measures

Outcome measures
Measure	Lemborexant-matched Placebo n=68 Participants Participants received a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Periods 1, 2, or 3.	Lemborexant 5 mg n=69 Participants Participants received a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Periods 1, 2, or 3.	Lemborexant 10 mg n=68 Participants Participants received a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Periods 1, 2, or 3.	Flurazepam 30 mg Participants received a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4.
Mean Change From Baseline in the Average Sleep Onset Latency (SOL) From Modified-Multiple Sleep Latency Test (M-MSLT) for Each Treatment in Treatment Periods 1 to 3 Baseline	18.25 minutes Standard Deviation 2.621	18.28 minutes Standard Deviation 2.61	18.25 minutes Standard Deviation 2.621	—
Mean Change From Baseline in the Average Sleep Onset Latency (SOL) From Modified-Multiple Sleep Latency Test (M-MSLT) for Each Treatment in Treatment Periods 1 to 3 Change at Day 2 After Each Treatment	-3.43 minutes Standard Deviation 4.424	-4.56 minutes Standard Deviation 4.693	-6.95 minutes Standard Deviation 4.967	—

SECONDARY outcome

Timeframe: Day 2 of each of three treatment periods that were separated by approximately 2 weeks (for a total of up to 6 weeks)

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

SOL is defined as the length of time that it takes to accomplish the transition from full wakefulness to sleep. The MSLT is a widely used method for objectively quantifying excessive, pathological, or pharmacologically induced residual sleepiness by measuring the number of minutes that it takes a participant to fall asleep. The MSLT was modified to include four SLTs, with the first starting at 45 minutes after morning wake time, and the subsequent three occurring at 30-minute intervals for a total of 4 SLT's per M-MSLT. Each SLT was scored to determine the latency in minutes (with precision to 0.5 minute) from lights off to sleep onset; trials during which sleep onset did not occur were assigned a latency of 20 minutes. The four SLTs for each participant were averaged to obtain the mean SOL.

Outcome measures

Outcome measures
Measure	Lemborexant-matched Placebo n=68 Participants Participants received a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Periods 1, 2, or 3.	Lemborexant 5 mg n=69 Participants Participants received a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Periods 1, 2, or 3.	Lemborexant 10 mg n=68 Participants Participants received a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Periods 1, 2, or 3.	Flurazepam 30 mg n=68 Participants Participants received a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4.
Number of Participants With an Average SOL of Less Than (<) 8.0 Minutes for Each Treatment	3 Participants	11 Participants	20 Participants	36 Participants

SECONDARY outcome

Timeframe: Day 2 of each of three treatment periods that are separated by approximately 2 weeks (for a total of up to 6 weeks)

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

Outcome measures

Outcome measures
Measure	Lemborexant-matched Placebo n=68 Participants Participants received a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Periods 1, 2, or 3.	Lemborexant 5 mg n=68 Participants Participants received a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Periods 1, 2, or 3.	Lemborexant 10 mg n=68 Participants Participants received a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Periods 1, 2, or 3.	Flurazepam 30 mg Participants received a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4.
Number of Participants Whose Treatment Difference (Under Either Dose of Lemborexant) Average SOL Score is More Than (>) 6.0 Minutes Shorter Than Placebo	9 Participants	20 Participants	35 Participants	—

SECONDARY outcome

Timeframe: Day 2 of each of three treatment periods that are separated by approximately 2 weeks (for a total of up to 6 weeks)

Outcome measures

Outcome measures
Measure	Lemborexant-matched Placebo n=68 Participants Participants received a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Periods 1, 2, or 3.	Lemborexant 5 mg n=68 Participants Participants received a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Periods 1, 2, or 3.	Lemborexant 10 mg n=68 Participants Participants received a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Periods 1, 2, or 3.	Flurazepam 30 mg Participants received a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4.
Number of Participants Whose Average SOL is <8.0 Minutes and >6.0 Minutes Shorter Than Placebo	4 Participants	13 Participants	25 Participants	—

SECONDARY outcome

Timeframe: Baseline, Day 2 of Treatment Period 4 (Week 6)

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

Outcome measures

Outcome measures
Measure	Lemborexant-matched Placebo n=68 Participants Participants received a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Periods 1, 2, or 3.	Lemborexant 5 mg Participants received a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Periods 1, 2, or 3.	Lemborexant 10 mg Participants received a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Periods 1, 2, or 3.	Flurazepam 30 mg Participants received a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4.
Mean Change From Baseline in the Average SOL From the M-MSLT in Treatment Period 4 Baseline	18.25 minutes Standard Deviation 2.621	—	—	—
Mean Change From Baseline in the Average SOL From the M-MSLT in Treatment Period 4 Change at Day 2 of Treatment Period 4	-9.49 minutes Standard Deviation 5.413	—	—	—

SECONDARY outcome

Timeframe: Days 2, 16 and 30 within 20 minutes after the end of 4th SLT (up to 155 minutes after wake time)

Population: The pharmacokinetic (PK) analysis set was the group of participants who received at least one dose of lemborexant and had at least one quantifiable postdose drug concentration. The PK analysis set where data at specified time points was available.

The MSLT is a widely used method for objectively quantifying excessive, pathological, or pharmacologically induced residual sleepiness by measuring the number of minutes that it takes a participant to fall asleep. The MSLT was modified to include four SLTs, with the first starting at 45 minutes after morning wake time, and the subsequent three occurring at 30-minute intervals for a total of 4 SLT's per M-MSLT.

Outcome measures

Outcome measures
Measure	Lemborexant-matched Placebo n=69 Participants Participants received a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Periods 1, 2, or 3.	Lemborexant 5 mg n=68 Participants Participants received a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Periods 1, 2, or 3.	Lemborexant 10 mg Participants received a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Periods 1, 2, or 3.	Flurazepam 30 mg Participants received a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4.
Mean Plasma Concentrations of Lemborexant and Metabolite M10 in the Morning Following M-MSLT Lemborexant: Day 2	2.285 nanogram per milliliter (ng/mL) Standard Deviation 1.426	6.423 nanogram per milliliter (ng/mL) Standard Deviation 3.262	—	—
Mean Plasma Concentrations of Lemborexant and Metabolite M10 in the Morning Following M-MSLT Metabolite M10: Day 2	1.246 nanogram per milliliter (ng/mL) Standard Deviation 0.792	2.582 nanogram per milliliter (ng/mL) Standard Deviation 0.959	—	—
Mean Plasma Concentrations of Lemborexant and Metabolite M10 in the Morning Following M-MSLT Lemborexant: Day 16	3.236 nanogram per milliliter (ng/mL) Standard Deviation 1.895	5.306 nanogram per milliliter (ng/mL) Standard Deviation 3.175	—	—
Mean Plasma Concentrations of Lemborexant and Metabolite M10 in the Morning Following M-MSLT Metabolite M10: Day 16	1.361 nanogram per milliliter (ng/mL) Standard Deviation 0.634	2.689 nanogram per milliliter (ng/mL) Standard Deviation 1.592	—	—
Mean Plasma Concentrations of Lemborexant and Metabolite M10 in the Morning Following M-MSLT Lemborexant: Day 30	2.020 nanogram per milliliter (ng/mL) Standard Deviation 1.446	5.293 nanogram per milliliter (ng/mL) Standard Deviation 4.293	—	—
Mean Plasma Concentrations of Lemborexant and Metabolite M10 in the Morning Following M-MSLT Metabolite M10: Day 30	0.994 nanogram per milliliter (ng/mL) Standard Deviation 0.639	2.304 nanogram per milliliter (ng/mL) Standard Deviation 1.534	—	—

SECONDARY outcome

Timeframe: From first dose of study drug up to Day 54

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

Outcome measures

Outcome measures
Measure	Lemborexant-matched Placebo n=68 Participants Participants received a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Periods 1, 2, or 3.	Lemborexant 5 mg n=69 Participants Participants received a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Periods 1, 2, or 3.	Lemborexant 10 mg n=68 Participants Participants received a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Periods 1, 2, or 3.	Flurazepam 30 mg n=68 Participants Participants received a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4.
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) That Led to Death and Study Drug Discontinuation TEAEs	2 Participants	5 Participants	8 Participants	5 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) That Led to Death and Study Drug Discontinuation SAEs	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) That Led to Death and Study Drug Discontinuation AEs Leading to Death	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) That Led to Death and Study Drug Discontinuation AEs Leading to Discontinuation	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From first dose of study drug up to Day 54

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

Outcome measures

Outcome measures
Measure	Lemborexant-matched Placebo n=68 Participants Participants received a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Periods 1, 2, or 3.	Lemborexant 5 mg n=69 Participants Participants received a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Periods 1, 2, or 3.	Lemborexant 10 mg n=68 Participants Participants received a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Periods 1, 2, or 3.	Flurazepam 30 mg n=68 Participants Participants received a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4.
Number of Participants With Clinically Significant Abnormal Laboratory Values	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From first dose of study drug up to Day 54

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

Outcome measures

Outcome measures
Measure	Lemborexant-matched Placebo n=68 Participants Participants received a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Periods 1, 2, or 3.	Lemborexant 5 mg n=69 Participants Participants received a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Periods 1, 2, or 3.	Lemborexant 10 mg n=68 Participants Participants received a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Periods 1, 2, or 3.	Flurazepam 30 mg n=68 Participants Participants received a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4.
Number of Participants With Clinically Significant Change From Baseline in Vital Signs Values	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From first dose of study drug up to Day 54

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

Outcome measures

Outcome measures
Measure	Lemborexant-matched Placebo n=68 Participants Participants received a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Periods 1, 2, or 3.	Lemborexant 5 mg n=69 Participants Participants received a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Periods 1, 2, or 3.	Lemborexant 10 mg n=68 Participants Participants received a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Periods 1, 2, or 3.	Flurazepam 30 mg n=68 Participants Participants received a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4.
Number of Participants With Clinically Significant Shifts From Baseline in Electrocardiogram (ECG) Parameters	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline up to Day 44 (Week 6)

Population: The PK analysis set was the group of participants who received at least one dose of E2006 and had at least one quantifiable postdose drug concentration. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.

Pearson correlation was used to calculate the relationship between PK concentration of lemborexant and sleepiness. The M-MSLT is a widely used method for objectively quantifying excessive, pathological, or pharmacologically induced residual sleepiness by measuring the number of minutes that it takes a participant to fall asleep. The MSLT was modified to include four SLTs, with the first starting at 45 minutes after morning wake time, and the subsequent three occurring at 30-minute intervals for a total of 4 SLT's per M-MSLT. Each SLT was scored to determine the latency in minutes (with precision to 0.5 minute) from lights off to sleep onset; trials during which sleep onset did not occur were assigned a latency of 20 minutes.

Outcome measures

Outcome measures
Measure	Lemborexant-matched Placebo n=62 Participants Participants received a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Periods 1, 2, or 3.	Lemborexant 5 mg Participants received a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Periods 1, 2, or 3.	Lemborexant 10 mg Participants received a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Periods 1, 2, or 3.	Flurazepam 30 mg Participants received a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4.
Relationship Between PK Concentrations of Lemborexant and Sleepiness as Measured by M-MSLT	-0.2746 correlation coefficient	—	—	—

Adverse Events

Lemborexant-matched Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Lemborexant 5 mg

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Lemborexant 10 mg

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Flurazepam 30 mg

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Lemborexant-matched Placebo n=68 participants at risk Participants received a single oral dose of lemborexant-matched placebo tablet, on Day 1 of Treatment Periods 1, 2, or 3.	Lemborexant 5 mg n=69 participants at risk Participants received a single oral dose of lemborexant 5 mg tablet, on Day 1 of Treatment Periods 1, 2, or 3.	Lemborexant 10 mg n=68 participants at risk Participants received a single oral dose of lemborexant 10 mg tablet, on Day 1 of Treatment Periods 1, 2, or 3.	Flurazepam 30 mg n=68 participants at risk Participants received a single oral dose of flurazepam 30 mg capsule on Day 1 of Treatment Period 4.
Gastrointestinal disorders Diarrhoea	0.00% 0/68 • From date of first dose of study drug up to Day 54	1.4% 1/69 • From date of first dose of study drug up to Day 54	0.00% 0/68 • From date of first dose of study drug up to Day 54	0.00% 0/68 • From date of first dose of study drug up to Day 54
Gastrointestinal disorders Dry mouth	0.00% 0/68 • From date of first dose of study drug up to Day 54	0.00% 0/69 • From date of first dose of study drug up to Day 54	1.5% 1/68 • From date of first dose of study drug up to Day 54	0.00% 0/68 • From date of first dose of study drug up to Day 54
Gastrointestinal disorders Dyspepsia	0.00% 0/68 • From date of first dose of study drug up to Day 54	0.00% 0/69 • From date of first dose of study drug up to Day 54	1.5% 1/68 • From date of first dose of study drug up to Day 54	0.00% 0/68 • From date of first dose of study drug up to Day 54
Gastrointestinal disorders Nausea	0.00% 0/68 • From date of first dose of study drug up to Day 54	0.00% 0/69 • From date of first dose of study drug up to Day 54	1.5% 1/68 • From date of first dose of study drug up to Day 54	0.00% 0/68 • From date of first dose of study drug up to Day 54
Infections and infestations Gastroenteritis	2.9% 2/68 • From date of first dose of study drug up to Day 54	0.00% 0/69 • From date of first dose of study drug up to Day 54	1.5% 1/68 • From date of first dose of study drug up to Day 54	0.00% 0/68 • From date of first dose of study drug up to Day 54
Infections and infestations Upper respiratory tract infection	0.00% 0/68 • From date of first dose of study drug up to Day 54	0.00% 0/69 • From date of first dose of study drug up to Day 54	1.5% 1/68 • From date of first dose of study drug up to Day 54	1.5% 1/68 • From date of first dose of study drug up to Day 54
Nervous system disorders Dysgeusia	0.00% 0/68 • From date of first dose of study drug up to Day 54	0.00% 0/69 • From date of first dose of study drug up to Day 54	0.00% 0/68 • From date of first dose of study drug up to Day 54	1.5% 1/68 • From date of first dose of study drug up to Day 54
Nervous system disorders Headache	0.00% 0/68 • From date of first dose of study drug up to Day 54	1.4% 1/69 • From date of first dose of study drug up to Day 54	0.00% 0/68 • From date of first dose of study drug up to Day 54	1.5% 1/68 • From date of first dose of study drug up to Day 54
Nervous system disorders Somnolence	0.00% 0/68 • From date of first dose of study drug up to Day 54	1.4% 1/69 • From date of first dose of study drug up to Day 54	4.4% 3/68 • From date of first dose of study drug up to Day 54	2.9% 2/68 • From date of first dose of study drug up to Day 54
Psychiatric disorders Anxiety	0.00% 0/68 • From date of first dose of study drug up to Day 54	1.4% 1/69 • From date of first dose of study drug up to Day 54	0.00% 0/68 • From date of first dose of study drug up to Day 54	0.00% 0/68 • From date of first dose of study drug up to Day 54
Psychiatric disorders Hypnopompic hallucination	0.00% 0/68 • From date of first dose of study drug up to Day 54	1.4% 1/69 • From date of first dose of study drug up to Day 54	0.00% 0/68 • From date of first dose of study drug up to Day 54	0.00% 0/68 • From date of first dose of study drug up to Day 54

Additional Information

Eisai Medical Information

Eisai Inc.

Phone: +1-888-274-2378

Email: [email protected]

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Principal investigator is a sponsor employee
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