The Effects of Lemborexant on the Ability to Sleep During Daytime

Inclusion Criteria:

Participants must fulfill all of the following inclusion criteria to be eligible for inclusion in this study:

1. Men or women aged between 20 and 65 years, inclusive

2. Be willing and able to give informed consent for study participation

3. Participants must not have done shiftwork in the past year

4. Normal vital signs values are: oral body temperature between 36.1 and 37.5 ºC (95and 99.5 °F), supine SBP between 90 and 140 mmHg inclusive; supine DBP between 55and 90 mmHg inclusive; heart rate between 50 and 100 bpm inclusive.

5. Be willing to comply with all study requirements and procedures for the duration ofthe study, including refraining from consuming alcohol 48 hours prior to eachexperimental visit and grapefruit products (juice or fruit itself), Seville orange,lime, pomelo, carambola and pomegranate during all the duration of the study (fromVisit 1 to Visit 4).

6. Women who:

• Are postmenopausal, with amenorrhea for at least 1 year before the screeningvisit, OR

• Are surgically sterile, OR

• If of childbearing potential agree to practice effective double barrier methodsof contraception, from the time of the signing of informed consent through thelast dose of study drug and for 30 days after dosing stops (1 ovulatory cycle),or agree to completely abstain from intercourse. Men with women partners of childbearing potential are also expected to practiceeffective barrier methods of contraception from the time of signing informed consentthrough the last dose of study drug and for 30 days after dosing stops.

7. Self-reported bedtime was between 9 pm and midnight on 4-7 nights per week.

Exclusion Criteria:

Participants must not meet any of the following exclusion criteria:

1. Body mass index > 32 as calculated from the participant's height (m) and weight (kg); weight (kg)/square height (m²)

2. Presence of a sleep disorder, such as a diagnosis of insomnia, narcolepsy, sleepparalysis, active somnambulism (history of childhood somnambulism is accepted),hypnagogic/ hypnopompic hallucinations, and REM behavior disorder, will be excludedbased on the clinical interview. For sleep apnea syndrome, an apnea-hypopnea index > 15 per hour of sleep on the first screening night will be used as an exclusioncriterion. For periodic limb movement disorder, an index of periodic limb movementsduring sleep associated with an arousal > 15 per hour of sleep on the firstscreening night will be used as an exclusion criterion.

3. History of epilepsy

4. Any previous serious head injury or stroke

5. Any evidence of psychiatric disorder (including Beck Depression Inventory [BDI] ≥ 20at screening, or a score of 3 on item related to suicidal ideas)

6. Evidence of any clinically significant, or unstable, acute or chronicallyprogressive medical or surgical disorder (including planned medical procedures thatmay impact sleep), or any condition that may interfere with the absorption,metabolism, distribution, or excretion of the study drug, or may affect theparticipant's safety

7. Clinically significant and abnormal electrocardiogram (ECG; including QTc ≥ 450 msfor males, 460 ms for females) or a history of cardiovascular disease includingpoorly controlled hypertension, ischemic heart disease, arrhythmia, or severe heartfailure

8. Severe hepatic impairment

9. Positive qualitative urine drug screen (opiates, cocaine, amphetamine, cannabinoids,barbiturates, phencyclidine, benzodiazepines, methadone, propoxyphene) and alcoholtest (breathalyzer), at screening and before each experimental visit

10. Current use of medications that are moderate or strong CYP3A4 inhibitors or inducersor CYP2B6 substrates (Appendix 1)

11. Use of any substance with psychotropic effects or properties known to affectsleep/wake, including hypnotics, neuroleptics, opioid derivatives, antihistamines,stimulants, antidepressants, within one week or five half-lives (whichever islonger) prior to PSG screening

12. Use of any over-the-counter sleep medications including tryptophan, valerian root (Valeriana officinalis), kava (Piper methysticum Forst), melatonin, St John's Wort (Hypericum perforatum), Alluna (herbal sleep supplement with valerian root), andhemp within one week or five half-lives (whichever is longer) prior to screening

13. Consumption of xanthine-containing beverages (i.e., tea, coffee, or cola) of morethan 5 cups or glasses per day

14. Participation in any other trial within 30 days before the screening visit

15. Any travel across more than one time zone in the month prior to screening at anytime during the study

16. Other exclusion criteria based on adverse events (AE) or serious adverse events (SAE) reported in the Investigator Brochure

17. Women who are pregnant, during the study or within one month after the study, or arebreastfeeding

18. Individuals may be excluded from participating in the study based on the clinician'sjudgement.

19. Participants with lactose or galactose intolerance (galactosemia orglucose-galactose malabsorption)