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

• Sponsor: Eisai Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01995838
• Collaborator: (none)
• Enrollment: 291
• Locations: 29
• Arms: 2
• Actual Duration (Months): 5.5
• Patients Per Site: 10
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

This is a multicenter, multiple dose, randomized, double-blind, placebo-controlled, parallel-group, Bayesian adaptive, dose response study in subjects with chronic insomnia. Subjects will be randomized to 1 of 6 doses of E2006 (1 mg, 2.5 mg, 5 mg, 10 mg, 15 mg, or 25 mg) or placebo.

Condition or Disease	Intervention/Treatment	Phase
Chronic Insomnia; Adults; Elderly	Drug: E2006; Drug: Placebo	Phase 2

Detailed Description

The study will have 2 phases, Prerandomization and Randomization. The Prerandomization Phase will last up to 21 days and will consist of a Screening Period (Days -21 to -2) and a Baseline Period (Day -1). Following the Baseline Period, all eligible subjects will be randomized, in a double-blind manner, to receive E2006 or placebo for 15 nights during the Treatment Period (Days 1 to 15), then all subjects will receive placebo, in a single-blind manner, for 2 nights (Days 16 to 17) during the Rebound Insomnia Assessment Period (Days 16 to 18). Subjects will not receive any treatment during the Follow-up Period (Days 19 to 29). All subjects will come to the clinic for screening procedures. During the Screening Period, subjects will complete the Sleep Diary each day. Polysomnographic sleep will be measured during the Screening Period on 2 consecutive nights between Day -9 and Day -3. These 8-hour polysomnograms (PSGs) will start at the median habitual bedtime calculated from responses on the Sleep Diary completed 7 days immediately prior to the first PSG night. Subjects may leave the clinic between the screening/baseline PSG nights.

Study Design

• Study Type: Interventional
• Actual Enrollment: 291 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Nov 13, 2013
• Actual Primary Completion Date: Apr 29, 2014
• Actual Study Completion Date: Apr 29, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: E2006 E2006 1 mg, 2.5 mg, 5 mg, 10 mg, 15 mg, or 25 mg, in tablet form, taken orally, 30 minutes prior to bedtime, each night for 15 consecutive nights	Drug: E2006; E2006 1 mg, 2.5 mg, 5 mg, 10 mg, 15 mg, or 25 mg, in tablet form, taken orally, 30 minutes prior to bedtime, each night for 15 consecutive nights
Placebo Comparator: Placebo E2006-matched placebo in tablet form, taken orally, 30 minutes prior to bedtime, each night for 15 consecutive nights	Drug: Placebo; E2006-matched placebo in tablet form, taken orally, 30 minutes prior to bedtime, each night for 15 consecutive nights

Outcome Measures

Primary Outcome Measures

1. Probability of Having Utility Function Greater Than (>) 1 Based on Bayesian Analysis [Baseline up to Day 3]

   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.

2. Mean Change From Baseline in Karolinska Sleepiness Scale (KSS) Score at End of Treatment [1 hour after morning wake time at Baseline and Days 15-16]

   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.

Secondary Outcome Measures

1. Mean Change From Baseline in Sleep Efficiency (SE) After Dosing on Days 1-2 and Days 14-15 [Baseline, Days 1-2, and Days 14-15]

   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.

2. Mean Change From Baseline in Latency to Persistent Sleep (LPS) After Dosing on Days 1-2 and Days 14-15 [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.

3. Mean Change From Baseline in Wakefulness After Sleep Onset (WASO) After Dosing on Days 1-2 and Days 14-15 [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.

4. 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 [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 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.

5. 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 [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.

6. 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 [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.

7. Rebound Insomnia: Mean Change From Baseline in Sleep Efficiency (SE) After Dosing on Days 16-17 [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.

8. Percentage of Participants With Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) [TEAEs: Baseline up to Day 30, SAEs: Baseline up to 30 days after last dose of study drug (up to 47 days)]

9. Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Parameters [Baseline up to Day 30]

10. Number of Participants With Clinically Significant Change From Baseline in Vital Signs [Baseline up to Day 30]

11. Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECGs) [Baseline up to Day 30]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

Subjects must meet all of the following criteria to be included in this study:

1. Male or female subjects age 18 to 80 years at the time of informed consent

2. Meets the 5th Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for Insomnia Disorder

3. Subjective Sleep Onset Latency (sSOL) typically greater than or equal to 30 minutes in the last 4 weeks and/or subjective WASO (sWASO) typically greater than or equal to 60 minutes in the last 4 weeks

4. Regular time in bed between 6.5 and 9.0 hours

5. Regular bedtime between 21:00 and 24:00 and regular waketime between 05:00 and 09:00

6. Insomnia Severity Index (ISI) score greater than or equal to 15 at Screening

7. Confirmation of current insomnia symptoms as determined from responses on the Sleep Diary completed for 7 nights prior to the first screening/baseline PSG

8. Objective (PSG) evidence of insomnia at the screening/baseline PSGs as follows:

9. LPS average greater than or equal to 30 minutes on the 2 consecutive screening/baseline PSGs, with neither night lesser than 15 minutes and/or

10. WASO average greater than or equal to 30 minutes on the 2 consecutive screening/baseline PSGs, with neither night lesser than 20 minutes

11. SE average lesser than or equal to 85% on the 2 consecutive screening/baseline PSGs, with neither night greater than 87.5%

12. Females of childbearing potential must not have had unprotected sexual intercourse within 30 days before study entry and must agree to use two highly effective method of contraception

13. Male subjects must have had a successful vasectomy (confirmed azoospermia) or they and their female partners must meet the criteria above (i.e., not of childbearing potential or practicing highly effective contraception throughout the study period and for 30 days after study drug discontinuation). No sperm donation is allowed during the study period and for 30 days after study drug discontinuation.

14. Provide written informed consent

15. Willing to stay in bed for at least 8 hours each night spent in the clinic

16. Willing and able to comply with all aspects of the protocol

Exclusion Criteria

Subjects who meet any of the following criteria will be excluded from this study:

1. Females who are pregnant (positive beta-human chorionic gonadotropin [B-hCG] test) or breastfeeding

2. Any lifetime diagnosis of sleep-related breathing disorder, periodic limb movement disorder, restless legs syndrome, nightmare disorder, sleep terror disorder, sleepwalking disorder, rapid eye movement (REM) behavior disorder, or narcolepsy

3. Aged 18 to 64 years: Apnea-Hypopnea Index greater than or equal to 10, or Periodic Limb Movements with Arousal Index greater than or equal to 10 on first (diagnostic) PSG night at Screening. Aged 65 to 80 years: Apnea-Hypopnea Index greater than 15, or Periodic Limb Movements with Arousal Index greater than 15 on first (diagnostic) PSG night at Screening

4. Beck Depression Inventory (BDI) - II score greater than 19 at Screening

5. Beck Anxiety Inventory (BAI) score greater than 15 at Screening

6. Used a prescription for any modality of treatment for insomnia, including cognitive behavioral therapy, within 2 weeks prior to screening/baseline PSG, or between Screening and Baseline

7. Used any medication or sleep aid with known effects on sleep, within 2 weeks prior to screening/baseline PSG, or between Screening and Baseline

8. Used any prohibited prescription or over-the-counter concomitant medications within the week prior to the first screening/baseline PSG.

9. Transmeridian travel across 3 or more time zones in the 2 weeks prior to Screening, or plans to travel across 3 or more time zones during study

10. Unwilling to limit caffeine consumption to lesser than or equal to 600 mg caffeine (approximately four 6-oz cups of caffeinated coffee, or three 12-oz caffeinated sodas, or three 8-oz caffeinated tea beverages), avoid caffeine after 18:00 throughout the study, and avoid caffeine after 13:00 on PSG visits

11. Unwilling to limit alcohol intake to two or fewer drinks per day throughout the study, or to refrain from any alcohol for 3 hours prior to bedtime while at home throughout the study, or any alcohol on days and nights spent in the clinic. A drink is defined as approximately 12 oz (360 mL) of beer, 4 oz (120 mL) of wine, or 1 oz (30 mL) of liquor.

12. Any subject that has a known history of malaria or has traveled to a country with known malarial risk (i.e., are designated as 'high' or 'moderate' risk country according to the list available at http://www.cdc.gov/malaria) within the last year.

13. A prolonged QT/QT interval corrected for heart rate (QTc) interval (QTc greater than 450 ms) as demonstrated by a repeated electrocardiogram (ECG) at Screening (repeated only if initial ECG indicates a QTc interval greater than 450 ms). A history of risk factors for torsade de pointes (e.g., heart failure, hypokalemia, family history of long QT Syndrome) or the use of concomitant medications that prolong the QT/QTc interval.

14. Any suicidal ideation with intent with or without a plan at Screening, Baseline, or within 6 months before Screening (i.e., answering "Yes" to questions 4 or 5 on the Suicidal Ideation section of the Columbia-Suicide Severity Rating Scale [C-SSRS])

15. Any lifetime suicidal behavior (per the Suicidal Behavior Section of the C-SSRS)

16. Evidence of clinically significant disease (e.g., cardiac, respiratory, gastrointestinal, renal disease) that in the opinion of the investigator(s) could affect the subject's safety or interfere with the study assessments

17. Hypersensitivity to the study drug or any of the excipients

18. Any history of a medical condition or a concomitant medical condition that in the opinion of the investigator(s) would compromise the subject's ability to safely complete the study

19. Scheduled for surgery during the study

20. Known to be human immunodeficiency virus (HIV) positive

21. Active viral hepatitis (B or C) as demonstrated by positive serology

22. Psychotic disorder(s) or unstable recurrent affective disorder(s) evident by use of antipsychotics or prior suicide attempt(s) within approximately the last 2 years

23. History of drug or alcohol dependency or abuse within approximately the last 2 years

24. Unwilling to refrain from use of illegal (or legalized) recreational drugs during the study or test positive for illegal (or legalized) drugs at Screening, Baseline, or Day 14

25. Currently enrolled in another clinical trial or used any investigational drug or device within 30 days or 5x the half-life, whichever is longer preceding informed consent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Glendale	Arizona	United States	85306
2		Phoenix	Arizona	United States	85006
3		Fountain Valley	California	United States	92708
4		Oceanside	California	United States	92054
5		San Diego	California	United States	92103
6		San Diego	California	United States	92123
7		Thousand Oaks	California	United States	91360
8		Colorado Springs	Colorado	United States	80907
9		Colorado Springs	Colorado	United States	80909
10		Brandon	Florida	United States	33511
11		Hallandale Beach	Florida	United States	33009
12		Hollywood	Florida	United States	33024
13		South Miami	Florida	United States	33143
14		Atlanta	Georgia	United States	30342
15		Chicago	Illinois	United States	60634
16		Chicago	Illinois	United States	60637
17		Overland Park	Kansas	United States	66212
18		Glen Burnie	Maryland	United States	21061
19		Las Vegas	Nevada	United States	89104
20		New York	New York	United States	10019
21		Raleigh	North Carolina	United States	27612
22		Cincinnati	Ohio	United States	45212
23		Cincinnati	Ohio	United States	45255
24		Philadelphia	Pennsylvania	United States	19118
25		Columbia	South Carolina	United States	29201-2953
26		Austin	Texas	United States	78731
27		Austin	Texas	United States	78744
28		Dallas	Texas	United States	75230
29		Vienna	Virginia	United States	22182

Sponsors and Collaborators

• Eisai Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eisai Inc.
• ClinicalTrials.gov Identifier: NCT01995838
• Other Study ID Numbers: E2006-G000-201
• First Posted: Nov 27, 2013
• Last Update Posted: Jan 31, 2020
• Last Verified: Nov 1, 2015

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Eisai Inc.: Chronic Insomnia; Adults; Elderly
• Additional relevant MeSH terms: Sleep Initiation and Maintenance Disorders

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 23 investigative sites in the United States from 13 Nov 2013 to 29 Apr 2014.
Pre-assignment Detail	A total of 616 participants were screened, of which 325 were screen failures and 291 were randomized to receive study treatment.

Arm/Group Title	Placebo	Lemborexant 1 Milligram (mg)	Lemborexant 2.5 mg	Lemborexant 5 mg	Lemborexant 10 mg	Lemborexant 15 mg	Lemborexant 25 mg
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.
Period Title: Overall Study
STARTED	56	32	27	38	32	56	50
COMPLETED	51	30	27	36	30	54	45
NOT COMPLETED	5	2	0	2	2	2	5

Baseline Characteristics

Arm/Group Title	Lemborexant 1 mg	Lemborexant 2.5 mg	Lemborexant 5 mg	Lemborexant 10 mg	Lemborexant 15 mg	Lemborexant 25 mg	Placebo	Total
Arm/Group Description	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.	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.	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.	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.	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.	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.	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 of all reporting groups
Overall Participants	32	27	38	32	56	50	56	291
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	53.3 (13.0)	49.7 (14.3)	51.1 (14.3)	47.1 (13.7)	44.0 (14.6)	48.9 (13.4)	47.1 (15.6)	48.3 (14.4)
Sex: Female, Male (Count of Participants)
Female	23 71.9%	17 63%	23 60.5%	20 62.5%	32 57.1%	31 62%	36 64.3%	182 62.5%
Male	9 28.1%	10 37%	15 39.5%	12 37.5%	24 42.9%	19 38%	20 35.7%	109 37.5%

Outcome Measures

1. Primary Outcome

Title	Probability of Having Utility Function Greater Than (>) 1 Based on Bayesian Analysis
Description	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.
Time Frame	Baseline up to Day 3

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Lemborexant 1 mg	Lemborexant 2.5 mg	Lemborexant 5 mg	Lemborexant 10 mg	Lemborexant 15 mg	Lemborexant 25 mg
Arm/Group Description	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.	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.	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.	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.	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.	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.
Measure Participants	32	27	38	32	56	50
Number [probability]	0.8789	0.8920	0.9032	0.9406	0.9866	0.9675

2. Primary Outcome

Title	Mean Change From Baseline in Karolinska Sleepiness Scale (KSS) Score at End of Treatment
Description	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.
Time Frame	1 hour after morning wake time at Baseline and Days 15-16

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Lemborexant 1 mg	Lemborexant 2.5 mg	Lemborexant 5 mg	Lemborexant 10 mg	Lemborexant 15 mg	Lemborexant 25 mg	Placebo
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.
Measure Participants	31	27	37	31	54	46	51
Least Squares Mean (Standard Error) [Units on a scale]	0.29 (0.219)	-0.10 (0.234)	0.20 (0.200)	-0.22 (0.219)	0.16 (0.166)	0.45 (0.180)	-0.23 (0.170)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 1 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0651
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.51
	Confidence Interval	(2-Sided) 95%; -0.03 to 1.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 2.5 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6490
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.13
	Confidence Interval	(2-Sided) 95%; -0.44 to 0.70
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 5 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1059
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.43
	Confidence Interval	(2-Sided) 95%; -0.09 to 0.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 10 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0. 9818
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 95%; -0. 54 to 0.55
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 15 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0. 1071
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.38
	Confidence Interval	(2-Sided) 95%; -0.08 to 0.85
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 25 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0063
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.68
	Confidence Interval	(2-Sided) 95%; 0.19 to 1.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Mean Change From Baseline in Sleep Efficiency (SE) After Dosing on Days 1-2 and Days 14-15
Description	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.
Time Frame	Baseline, Days 1-2, and Days 14-15

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Lemborexant 1 mg	Lemborexant 2.5 mg	Lemborexant 5 mg	Lemborexant 10 mg	Lemborexant 15 mg	Lemborexant 25 mg	Placebo
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.
Measure Participants	32	27	38	32	56	50	56
Days 1-2	18.72 (1.366)	18.59 (1.487)	19.89 (1.250)	22.25 (1.361)	24.22 (1.029)	24.28 (1.091)	14.16 (1.031)
Days 14-15	14.43 (1.428)	18.02 (1.528)	19.85 (1.302)	21.87 (1.421)	21.97 (1.077)	22.96 (1.169)	14.08 (1.100)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 1 mg, Placebo
	Comments	Days 1-2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0083
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	4.57
	Confidence Interval	(2-Sided) 95%; 1.19 to 7.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 2.5 mg, Placebo
	Comments	Days 1-2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0151
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	4.44
	Confidence Interval	(2-Sided) 95%; 0.86 to 8.01
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 5 mg, Placebo
	Comments	Days 1-2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	5.74
	Confidence Interval	(2-Sided) 95%; 2.54 to 8.93
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 10 mg, Placebo
	Comments	Days 1-2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	8.09
	Confidence Interval	(2-Sided) 95%; 4.73 to 11.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 15 mg, Placebo
	Comments	Days 1-2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	10.06
	Confidence Interval	(2-Sided) 95%; 7.20 to 12.93
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 25 mg, Placebo
	Comments	Days 1-2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	10.13
	Confidence Interval	(2-Sided) 95%; 7.18 to 13.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 1 mg, Placebo
	Comments	Days 14-15
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8505
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.34
	Confidence Interval	(2-Sided) 95%; -3.22 to 3.90
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 2.5 mg, Placebo
	Comments	Days 14-15
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0380
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.94
	Confidence Interval	(2-Sided) 95%; 0.22 to 7.66
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 5 mg, Placebo
	Comments	Days 14-15
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0008
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	5.76
	Confidence Interval	(2-Sided) 95%; 2.40 to 9.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 10 mg, Placebo
	Comments	Days 14-15
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	7.78
	Confidence Interval	(2-Sided) 95%; 4.24 to 11.32
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 15 mg, Placebo
	Comments	Days 14-15
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	7.89
	Confidence Interval	(2-Sided) 95%; 4.86 to 10.92
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 25 mg, Placebo
	Comments	Days 14-15
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	8.87
	Confidence Interval	(2-Sided) 95%; 5.72 to 12.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Mean Change From Baseline in Latency to Persistent Sleep (LPS) After Dosing on Days 1-2 and Days 14-15
Description	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.
Time Frame	Baseline, Days 1-2, and Days 14-15

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Lemborexant 1 mg	Lemborexant 2.5 mg	Lemborexant 5 mg	Lemborexant 10 mg	Lemborexant 15 mg	Lemborexant 25 mg	Placebo
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.
Measure Participants	32	27	38	32	56	50	56
Days 1-2	-42.92 (41.855)	-52.74 (50.149)	-47.72 (39.389)	-46.80 (46.106)	-51.59 (36.728)	-50.16 (43.140)	-22.90 (44.457)
Days 14-15	-41.23 (34.618)	-54.24 (44.918)	-51.86 (41.994)	-56.14 (45.553)	-51.95 (41.926)	-50.79 (40.160)	-22.43 (29.045)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 1 mg, Placebo
	Comments	Days 1-2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1407
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	Geometric Mean Ratio
	Estimated Value	0.77
	Confidence Interval	(2-Sided) 95%; 0.54 to 1.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 2.5 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments	Days 1-2
Statistical Test of Hypothesis	p-Value	0.0018
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	Geometric Mean Ratio
	Estimated Value	0.55
	Confidence Interval	(2-Sided) 95%; 0.38 to 0.80
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 5 mg, Placebo
	Comments	Days 1-2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0025
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	Geometric Mean Ratio
	Estimated Value	0.60
	Confidence Interval	(2-Sided) 95%; 0.43 to 0.83
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 10 mg, Placebo
	Comments	Days 1-2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0006
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	Geometric Mean Ratio
	Estimated Value	0.54
	Confidence Interval	(2-Sided) 95%; 0.38 to 0.76
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 15 mg, Placebo
	Comments	Days 1-2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	Geometric Mean Ratio
	Estimated Value	0.52
	Confidence Interval	(2-Sided) 95%; 0.38 to 0.70
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 25 mg, Placebo
	Comments	Days 1-2:
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	Geometric Mean Ratio
	Estimated Value	0.39
	Confidence Interval	(2-Sided) 95%; 0.29 to 0.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 1 mg, Placebo
	Comments	Days 14-15
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1158
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	Geometric Mean Ratio
	Estimated Value	0.73
	Confidence Interval	(2-Sided) 95%; 0.49 to 1.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 2.5 mg, Placebo
	Comments	Days 14-15
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0010
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	Geometric Mean Ratio
	Estimated Value	0.49
	Confidence Interval	(2-Sided) 95%; 0.33 to 0.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 5 mg, Placebo
	Comments	Days 14-15
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	Geometric Mean Ratio
	Estimated Value	0.47
	Confidence Interval	(2-Sided) 95%; 0.32 to 0.69
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 10 mg, Placebo
	Comments	Days 14-15
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	Geometric Mean Ratio
	Estimated Value	0.32
	Confidence Interval	(2-Sided) 95%; 0.21 to 0.47
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 15 mg, Placebo
	Comments	Days 14-15
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	Geometric Mean Ratio
	Estimated Value	0.41
	Confidence Interval	(2-Sided) 95%; 0.29 to 0.57
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 25 mg, Placebo
	Comments	Days 14-15
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	Geometric Mean Ratio
	Estimated Value	0.34
	Confidence Interval	(2-Sided) 95%; 0.24 to 0.48
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Mean Change From Baseline in Wakefulness After Sleep Onset (WASO) After Dosing on Days 1-2 and Days 14-15
Description	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.
Time Frame	Baseline, Days 1-2, and Days 14-15

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Lemborexant 1 mg	Lemborexant 2.5 mg	Lemborexant 5 mg	Lemborexant 10 mg	Lemborexant 15 mg	Lemborexant 25 mg	Placebo
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.
Measure Participants	32	27	38	32	56	50	56
Days 1-2	-52.11 (5.441)	-43.33 (5.915)	-52.29 (5.423)	-60.84 (1.302)	-70.38 (4.103)	-66.87 (4.342)	-41.03 (4.095)
Days 14-15	-32.46 (6.159)	-40.47 (6.581)	-48.84 (5.609)	-52.88 (6.129)	-58.95 (4.651)	-59.67 (5.039)	-38.15 (4.728)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 1 mg, Placebo
	Comments	Days 1-2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1050
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-11.08
	Confidence Interval	(2-Sided) 95%; -24.48 to 2.33
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 2.5 mg, Placebo
	Comments	Days 1-2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7501
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.29
	Confidence Interval	(2-Sided) 95%; -16.46 to 11.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 5 mg, Placebo
	Comments	Days 1-2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0818
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-11.26
	Confidence Interval	(2-Sided) 95%; -23.94 to 1.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 10 mg, Placebo
	Comments	Days 1-2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0038
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-19.81
	Confidence Interval	(2-Sided) 95%; -33.18 to -6.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 15 mg, Placebo
	Comments	Days 1-2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-29.34
	Confidence Interval	(2-Sided) 95%; -40.75 to 17.93
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 25 mg, Placebo
	Comments	Days 1-2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-25.84
	Confidence Interval	(2-Sided) 95%; -37.59 to -14.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 1 mg, Placebo
	Comments	Days 14-15
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4642
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.4642
	Confidence Interval	(2-Sided) 95%; -9.60 to 20.98
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 2.5 mg, Placebo
	Comments	Days 14-15
	Type of Statistical Test	Superiority
	Comments	Baseline value and treatment as covariates.
Statistical Test of Hypothesis	p-Value	0.7754
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.31
	Confidence Interval	(2-Sided) 95%; -18.27 to 13.64
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 5 mg, Placebo
	Comments	Days 14-15
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1461
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-10.69
	Confidence Interval	(2-Sided) 95%; -25.14 to 3.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 10 mg, Placebo
	Comments	Days 14-15
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0581
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-14.73
	Confidence Interval	(2-Sided) 95%; -29.97 to 0.51
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 15 mg, Placebo
	Comments	Days 14-15
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0019
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-20.80
	Confidence Interval	(2-Sided) 95%; -33.86 to -7.74
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 25 mg, Placebo
	Comments	Days 14-15
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0020
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-21.52
	Confidence Interval	(2-Sided) 95%; -35.12 to -7.91
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	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
Description	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.
Time Frame	Baseline, Days 1-2, and Days 14-15

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Lemborexant 1 mg	Lemborexant 2.5 mg	Lemborexant 5 mg	Lemborexant 10 mg	Lemborexant 15 mg	Lemborexant 25 mg	Placebo
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.
Measure Participants	31	27	37	31	54	46	52
Mean (Standard Deviation) [percentage of sleep time]	-4.04 (8.194)	-0.54 (10.505)	0.06 (6.888)	-0.68 (6.883)	-2.33 (6.600)	-2.15 (5.388)	-1.05 (7.192)

7. Secondary Outcome

Title	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
Description	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.
Time Frame	Baseline and Days 1-2, and Days 14-15

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Lemborexant 1 mg	Lemborexant 2.5 mg	Lemborexant 5 mg	Lemborexant 10 mg	Lemborexant 15 mg	Lemborexant 25 mg	Placebo
Arm/Group Description	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.	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.	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.	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.	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.	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.	Days 1 to 15: Three E2006-matched placebo tablets were taken orally, 30 minutes before bedtime, each night for 15 consecutive nights. Days 16 to 18: Two E2006-matched placebo tablets were taken for 2 consecutive nights. Days 10 to 30: No study drug, E2006 or placebo, was taken.
Measure Participants	31	27	37	31	54	46	52
Mean (Standard Deviation) [minutes]	2.71 (24.333)	-1.50 (22.120)	-4.60 (22.337)	-7.93 (17.415)	-1.11 (24.568)	1.38 (12.046)	0.57 (40.855)

8. Secondary Outcome

Title	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
Description	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.
Time Frame	Baseline, Days 1-2, and Days 14-15

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Lemborexant 1 mg	Lemborexant 2.5 mg	Lemborexant 5 mg	Lemborexant 10 mg	Lemborexant 15 mg	Lemborexant 25 mg	Placebo
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.
Measure Participants	31	27	36	31	54	45	52
Mean (Standard Deviation) [minutes]	17.98 (34.299)	2.16 (44.054)	2.68 (29.726)	9.30 (25.890)	11.76 (26.187)	9.28 (23.119)	5.99 (31.417)

9. Secondary Outcome

Title	Rebound Insomnia: Mean Change From Baseline in Sleep Efficiency (SE) After Dosing on Days 16-17
Description	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.
Time Frame	Baseline and Days 16-17

Outcome Measure Data

Analysis Population Description

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 timepoint.

Arm/Group Title	Lemborexant 1 mg	Lemborexant 2.5 mg	Lemborexant 5 mg	Lemborexant 10 mg	Lemborexant 15 mg	Lemborexant 25 mg	Placebo
Arm/Group Description	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.	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.	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.	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.	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.	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.	Days 1 to 15: Three E2006-matched placebo tablets were taken orally, 30 minutes before bedtime, each night for 15 consecutive nights. Days 16 to 18: Two E2006-matched placebo tablets were taken for 2 consecutive nights. Days 10 to 30: No study drug, E2006 or placebo, was taken.
Measure Participants	31	27	36	31	54	45	52
Least Squares Mean (Standard Error) [percentage of sleep time]	13.12 (1.661)	15.53 (1.777)	17.67 (1.535)	13.78 (1.653)	18.58 (1.253)	17.12 (1.374)	16.17 (1.280)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 1 mg, Placebo
	Comments	Days 16-17
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1483
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-3.05
	Confidence Interval	(2-Sided) 95%; -7.20 to 1.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 2.5 mg, Placebo
	Comments	Days 16-17
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7720
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.64
	Confidence Interval	(2-Sided) 95%; -4.96 to 3.69
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 5 mg, Placebo
	Comments	Days 16-17
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4548
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.50
	Confidence Interval	(2-Sided) 95%; -2.44 to 5.44
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 10 mg, Placebo
	Comments	Days 16-17
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2530
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.39
	Confidence Interval	(2-Sided) 95%; -6.51 to 1.72
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 15 mg, Placebo
	Comments	Days 16-17
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1794
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.41
	Confidence Interval	(2-Sided) 95%; -1.11 to 5.93
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Lemborexant 25 mg, Placebo
	Comments	Days 16-17
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6148
	Comments
	Method	ANCOVA
	Comments	Baseline value and treatment as covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 95%; -2.74 to 4.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Percentage of Participants With Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)
Time Frame	TEAEs: Baseline up to Day 30, SAEs: Baseline up to 30 days after last dose of study drug (up to 47 days)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Lemborexant 1 mg	Lemborexant 2.5 mg	Lemborexant 5 mg	Lemborexant 10 mg	Lemborexant 15 mg	Lemborexant 25 mg	Placebo
Arm/Group Description	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.	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.	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.	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.	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.	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.	Days 1 to 15: Three E2006-matched placebo tablets were taken orally, 30 minutes before bedtime, each night for 15 consecutive nights. Days 16 to 18: Two E2006-matched placebo tablets were taken for 2 consecutive nights. Days 10 to 30: No study drug, E2006 or placebo, was taken.
Measure Participants	32	27	38	32	56	50	56
TEAE	34.4 107.5%	40.7 150.7%	42.1 110.8%	59.4 185.6%	55.4 98.9%	60.0 120%	37.5 67%
SAE	0 0%	0 0%	0 0%	0 0%	0 0%	2.0 4%	1.8 3.2%

11. Secondary Outcome

Title	Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Parameters
Time Frame	Baseline up to Day 30

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Lemborexant 1 mg	Lemborexant 2.5 mg	Lemborexant 5 mg	Lemborexant 10 mg	Lemborexant 15 mg	Lemborexant 25 mg	Placebo
Arm/Group Description	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.	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.	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.	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.	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.	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.	Days 1 to 15: Three E2006-matched placebo tablets were taken orally, 30 minutes before bedtime, each night for 15 consecutive nights. Days 16 to 18: Two E2006-matched placebo tablets were taken for 2 consecutive nights. Days 10 to 30: No study drug, E2006 or placebo, was taken.
Measure Participants	32	27	38	32	56	50	56
Number [participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

12. Secondary Outcome

Title	Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Time Frame	Baseline up to Day 30

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Lemborexant 1 mg	Lemborexant 2.5 mg	Lemborexant 5 mg	Lemborexant 10 mg	Lemborexant 15 mg	Lemborexant 25 mg	Placebo
Arm/Group Description	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.	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.	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.	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.	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.	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.	Days 1 to 15: Three E2006-matched placebo tablets were taken orally, 30 minutes before bedtime, each night for 15 consecutive nights. Days 16 to 18: Two E2006-matched placebo tablets were taken for 2 consecutive nights. Days 10 to 30: No study drug, E2006 or placebo, was taken.
Measure Participants	32	27	38	32	56	50	56
Number [participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

13. Secondary Outcome

Title	Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECGs)
Time Frame	Baseline up to Day 30

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Lemborexant 1 mg	Lemborexant 2.5 mg	Lemborexant 5 mg	Lemborexant 10 mg	Lemborexant 15 mg	Lemborexant 25 mg	Placebo
Arm/Group Description	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.	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.	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.	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.	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.	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.	Days 1 to 15: Three E2006-matched placebo tablets were taken orally, 30 minutes before bedtime, each night for 15 consecutive nights. Days 16 to 18: Two E2006-matched placebo tablets were taken for 2 consecutive nights. Days 10 to 30: No study drug, E2006 or placebo, was taken.
Measure Participants	32	27	38	32	56	50	56
Number [participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

Adverse Events

Time Frame	TEAEs: Baseline up to Day 30, SAEs: Baseline up to 30 days after last dose of study drug (up to 47 days)
Adverse Event Reporting Description	Safety analysis set included participants who received at least one dose of study drug and had at least one postdose safety assessment.
Arm/Group Title	Lemborexant 1 mg		Lemborexant 2.5 mg		Lemborexant 5 mg		Lemborexant 10 mg		Lemborexant 15 mg		Lemborexant 25 mg		Placebo
Arm/Group Description	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.		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.		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.		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.		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.		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.		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.
All Cause Mortality
	Lemborexant 1 mg		Lemborexant 2.5 mg		Lemborexant 5 mg		Lemborexant 10 mg		Lemborexant 15 mg		Lemborexant 25 mg		Placebo
	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	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		0/50 (0%)		0/56 (0%)
Serious Adverse Events
	Lemborexant 1 mg		Lemborexant 2.5 mg		Lemborexant 5 mg		Lemborexant 10 mg		Lemborexant 15 mg		Lemborexant 25 mg		Placebo
	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	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		1/50 (2%)		1/56 (1.8%)
Metabolism and nutrition disorders
Hyperkalemia	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		0/50 (0%)		1/56 (1.8%)
Nervous system disorders
Grand Mal Convulsion	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		1/50 (2%)		0/56 (0%)
Other (Not Including Serious) Adverse Events
	Lemborexant 1 mg		Lemborexant 2.5 mg		Lemborexant 5 mg		Lemborexant 10 mg		Lemborexant 15 mg		Lemborexant 25 mg		Placebo
	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	11/32 (34.4%)		11/27 (40.7%)		16/38 (42.1%)		19/32 (59.4%)		31/56 (55.4%)		30/50 (60%)		21/56 (37.5%)
Cardiac disorders
Sinus bradycardia	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		0/50 (0%)		1/56 (1.8%)
Ear and labyrinth disorders
Ear pain	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		1/50 (2%)		0/56 (0%)
Hyperacusis	0/32 (0%)		0/27 (0%)		1/38 (2.6%)		0/32 (0%)		0/56 (0%)		0/50 (0%)		0/56 (0%)
Vertigo	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		1/50 (2%)		0/56 (0%)
Eye disorders
Eye pain	0/32 (0%)		0/27 (0%)		1/38 (2.6%)		0/32 (0%)		0/56 (0%)		1/50 (2%)		0/56 (0%)
Vision blurred	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		1/56 (1.8%)		1/50 (2%)		0/56 (0%)
Abnormal sensation in eye	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		1/56 (1.8%)		1/50 (2%)		0/56 (0%)
Blepharospasm	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		1/56 (1.8%)		0/50 (0%)		0/56 (0%)
Excessive eye blinking	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		0/50 (0%)		1/56 (1.8%)
Gastrointestinal disorders
Dry mouth	1/32 (3.1%)		0/27 (0%)		0/38 (0%)		1/32 (3.1%)		2/56 (3.6%)		2/50 (4%)		2/56 (3.6%)
Diarrhoea	0/32 (0%)		0/27 (0%)		1/38 (2.6%)		1/32 (3.1%)		1/56 (1.8%)		1/50 (2%)		0/56 (0%)
Nausea	0/32 (0%)		1/27 (3.7%)		0/38 (0%)		0/32 (0%)		1/56 (1.8%)		1/50 (2%)		3/56 (5.4%)
Abdominal pain	0/32 (0%)		0/27 (0%)		0/38 (0%)		1/32 (3.1%)		1/56 (1.8%)		0/50 (0%)		0/56 (0%)
Gastrooesophageal reflux disease	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		2/56 (3.6%)		0/50 (0%)		0/56 (0%)
Abdominal discomfort	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		1/56 (1.8%)		0/50 (0%)		1/56 (1.8%)
Abdominal distension	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		1/56 (1.8%)		0/50 (0%)		0/56 (0%)
Constipation	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		1/50 (2%)		0/56 (0%)
Food poisoning	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		1/50 (2%)		0/56 (0%)
Toothache	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		0/50 (0%)		1/56 (1.8%)
Vomiting	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		0/50 (0%)		1/56 (1.8%)
General disorders
Feeling drunk	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		3/50 (6%)		0/56 (0%)
Chills	0/32 (0%)		0/27 (0%)		0/38 (0%)		1/32 (3.1%)		1/56 (1.8%)		0/50 (0%)		0/56 (0%)
Pyrexia	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		2/50 (4%)		0/56 (0%)
Application site dermatitis	1/32 (3.1%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		0/50 (0%)		0/56 (0%)
Asthenia	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		1/50 (2%)		0/56 (0%)
Energy increased	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		1/50 (2%)		0/56 (0%)
Fatigue	0/32 (0%)		0/27 (0%)		1/38 (2.6%)		0/32 (0%)		0/56 (0%)		0/50 (0%)		0/56 (0%)
Irritability	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		1/50 (2%)		0/56 (0%)
Malaise	0/32 (0%)		0/27 (0%)		1/38 (2.6%)		0/32 (0%)		0/56 (0%)		0/50 (0%)		0/56 (0%)
Application site bruise	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		0/50 (0%)		1/56 (1.8%)
Infections and infestations
Upper respiratory tract infection	0/32 (0%)		1/27 (3.7%)		0/38 (0%)		1/32 (3.1%)		1/56 (1.8%)		0/50 (0%)		0/56 (0%)
Viral upper respiratory tract infection	1/32 (3.1%)		0/27 (0%)		0/38 (0%)		1/32 (3.1%)		0/56 (0%)		0/50 (0%)		0/56 (0%)
Influenza	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		1/50 (2%)		0/56 (0%)
Nasopharyngitis	0/32 (0%)		0/27 (0%)		1/38 (2.6%)		0/32 (0%)		0/56 (0%)		0/50 (0%)		0/56 (0%)
Sinusitis	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		1/50 (2%)		0/56 (0%)
Tooth abscess	1/32 (3.1%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		0/50 (0%)		0/56 (0%)
Acute sinusitis	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		0/50 (0%)		1/56 (1.8%)
Injury, poisoning and procedural complications
Contusion	1/32 (3.1%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		0/50 (0%)		0/56 (0%)
Excoriation	0/32 (0%)		0/27 (0%)		0/38 (0%)		1/32 (3.1%)		0/56 (0%)		0/50 (0%)		0/56 (0%)
Joint dislocation	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		1/50 (2%)		0/56 (0%)
Investigations
Alanine aminotransferase increased	0/32 (0%)		0/27 (0%)		0/38 (0%)		1/32 (3.1%)		0/56 (0%)		1/50 (2%)		0/56 (0%)
Aspartate aminotransferase increased	0/32 (0%)		0/27 (0%)		0/38 (0%)		1/32 (3.1%)		0/56 (0%)		1/50 (2%)		0/56 (0%)
Neutrophil count decreased	0/32 (0%)		1/27 (3.7%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		1/50 (2%)		0/56 (0%)
Blood pressure increased	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		1/50 (2%)		0/56 (0%)
Blood triglycerides increased	0/32 (0%)		1/27 (3.7%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		0/50 (0%)		0/56 (0%)
White blood cell count decreased	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		1/50 (2%)		0/56 (0%)
Metabolism and nutrition disorders
Hypercholesterolaemia	0/32 (0%)		1/27 (3.7%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		0/50 (0%)		0/56 (0%)
Hyperkalaemia	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		1/56 (1.8%)		0/50 (0%)		1/56 (1.8%)
Hypertriglyceridaemia	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		1/50 (2%)		0/56 (0%)
Increased appetite	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		1/56 (1.8%)		0/50 (0%)		0/56 (0%)
Decreased appetite	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		0/50 (0%)		1/56 (1.8%)
Musculoskeletal and connective tissue disorders
Back pain	0/32 (0%)		1/27 (3.7%)		0/38 (0%)		1/32 (3.1%)		3/56 (5.4%)		0/50 (0%)		0/56 (0%)
Myalgia	0/32 (0%)		0/27 (0%)		3/38 (7.9%)		1/32 (3.1%)		1/56 (1.8%)		0/50 (0%)		0/56 (0%)
Muscle twitching	0/32 (0%)		1/27 (3.7%)		1/38 (2.6%)		0/32 (0%)		1/56 (1.8%)		0/50 (0%)		0/56 (0%)
Muscular weakness	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		2/50 (4%)		0/56 (0%)
Muscle spasms	0/32 (0%)		0/27 (0%)		1/38 (2.6%)		0/32 (0%)		0/56 (0%)		0/50 (0%)		1/56 (1.8%)
Musculoskeletal pain	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		1/50 (2%)		0/56 (0%)
Arthralgia	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		0/50 (0%)		1/56 (1.8%)
Musculoskeletal discomfort	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		0/50 (0%)		1/56 (1.8%)
Musculoskeletal stiffness	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		0/50 (0%)		1/56 (1.8%)
Nervous system disorders
Somnolence	1/32 (3.1%)		1/27 (3.7%)		2/38 (5.3%)		4/32 (12.5%)		10/56 (17.9%)		11/50 (22%)		0/56 (0%)
Headache	3/32 (9.4%)		3/27 (11.1%)		3/38 (7.9%)		3/32 (9.4%)		6/56 (10.7%)		5/50 (10%)		3/56 (5.4%)
Sleep paralysis	0/32 (0%)		0/27 (0%)		1/38 (2.6%)		3/32 (9.4%)		4/56 (7.1%)		2/50 (4%)		0/56 (0%)
Dizziness	0/32 (0%)		1/27 (3.7%)		2/38 (5.3%)		0/32 (0%)		2/56 (3.6%)		1/50 (2%)		3/56 (5.4%)
Syncope	1/32 (3.1%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		1/50 (2%)		0/56 (0%)
Amnesia	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		1/50 (2%)		0/56 (0%)
Cataplexy	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		1/56 (1.8%)		0/50 (0%)		0/56 (0%)
Disturbance in attention	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		1/50 (2%)		0/56 (0%)
Dysgeusia	0/32 (0%)		0/27 (0%)		1/38 (2.6%)		0/32 (0%)		0/56 (0%)		0/50 (0%)		0/56 (0%)
Grand mal convulsion	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		1/50 (2%)		0/56 (0%)
Sedation	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		1/50 (2%)		0/56 (0%)
Sleep phase rhythm disturbance	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		1/50 (2%)		0/56 (0%)
Balance disorder	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		0/50 (0%)		1/56 (1.8%)
Migraine	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		0/50 (0%)		1/56 (1.8%)
Paraesthesia	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		0/50 (0%)		1/56 (1.8%)
Psychiatric disorders
Rapid eye movements sleep abnormal	0/32 (0%)		2/27 (7.4%)		1/38 (2.6%)		1/32 (3.1%)		3/56 (5.4%)		2/50 (4%)		2/56 (3.6%)
Nightmare	0/32 (0%)		0/27 (0%)		1/38 (2.6%)		3/32 (9.4%)		4/56 (7.1%)		0/50 (0%)		0/56 (0%)
Abnormal dreams	2/32 (6.3%)		0/27 (0%)		1/38 (2.6%)		3/32 (9.4%)		0/56 (0%)		0/50 (0%)		0/56 (0%)
Hypnagogic hallucination	0/32 (0%)		0/27 (0%)		1/38 (2.6%)		1/32 (3.1%)		2/56 (3.6%)		1/50 (2%)		0/56 (0%)
Anxiety	0/32 (0%)		0/27 (0%)		2/38 (5.3%)		1/32 (3.1%)		0/56 (0%)		1/50 (2%)		1/56 (1.8%)
Elevated mood	1/32 (3.1%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		1/50 (2%)		0/56 (0%)
Anger	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		1/56 (1.8%)		0/50 (0%)		0/56 (0%)
Bruxism	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		1/56 (1.8%)		0/50 (0%)		0/56 (0%)
Depression	0/32 (0%)		0/27 (0%)		0/38 (0%)		1/32 (3.1%)		0/56 (0%)		0/50 (0%)		0/56 (0%)
Euphoric mood	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		1/56 (1.8%)		0/50 (0%)		0/56 (0%)
Hypervigilance	1/32 (3.1%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		0/50 (0%)		2/56 (3.6%)
Restlessness	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		1/50 (2%)		0/56 (0%)
Sleep talking	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		1/56 (1.8%)		0/50 (0%)		0/56 (0%)
Renal and urinary disorders
Micturition urgency	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		1/50 (2%)		0/56 (0%)
Pollakiuria	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		1/56 (1.8%)		0/50 (0%)		0/56 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		1/56 (1.8%)		0/50 (0%)		0/56 (0%)
Diaphragmatic disorder	0/32 (0%)		0/27 (0%)		0/38 (0%)		1/32 (3.1%)		0/56 (0%)		0/50 (0%)		0/56 (0%)
Oropharyngeal pain	0/32 (0%)		0/27 (0%)		1/38 (2.6%)		0/32 (0%)		0/56 (0%)		0/50 (0%)		0/56 (0%)
Pulmonary congestion	0/32 (0%)		0/27 (0%)		0/38 (0%)		1/32 (3.1%)		0/56 (0%)		0/50 (0%)		0/56 (0%)
Asthma	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		0/50 (0%)		1/56 (1.8%)
Rhinorrhoea	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		0/50 (0%)		1/56 (1.8%)
Skin and subcutaneous tissue disorders
Photosensitivity reaction	0/32 (0%)		0/27 (0%)		1/38 (2.6%)		0/32 (0%)		0/56 (0%)		0/50 (0%)		0/56 (0%)
Pruritus	0/32 (0%)		0/27 (0%)		0/38 (0%)		1/32 (3.1%)		0/56 (0%)		0/50 (0%)		0/56 (0%)
Rash maculo-papular	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		1/50 (2%)		0/56 (0%)
Skin hyperpigmentation	0/32 (0%)		0/27 (0%)		0/38 (0%)		1/32 (3.1%)		0/56 (0%)		0/50 (0%)		0/56 (0%)
Onychoclasis	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		0/50 (0%)		1/56 (1.8%)
Rash	0/32 (0%)		0/27 (0%)		0/38 (0%)		0/32 (0%)		0/56 (0%)		0/50 (0%)		1/56 (1.8%)

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.