Study to Evaluate the Effect of Lemborexant Versus Placebo on Driving Performance in Healthy Adult and Elderly Subjects
Study to Evaluate the Effect of Lemborexant Versus Placebo on Driving Performance in Healthy Adult and Elderly Subjects
This is a randomized, double-blind, placebo- and active-controlled, 4-period crossover study
 of lemborexant in healthy adult and elderly subjects to evaluate driving performance
The study will have 2 phases, Prerandomization and Randomization. The Prerandomization Phase
 will consist of 2 periods that will last up to a maximum of 21 days: Screening and Baseline.
 The Randomization Phase will comprise of four, 9-day treatment periods (Treatment Period 1 -
 Treatment Period 4) with a minimum 14-day washout between treatment periods, and a follow-up
 interval of at least 14 days after Treatment Period 4 before the end-of-study (EOS) visit.
 Participants will be randomized to 1 of 12 sequences in an incomplete blocks design.
Inclusion Criteria:

 1. Healthy, male or female, aged 21 years or older at Screening

 2. Regular time spent in bed between 7.0 and 8.5 hours per night

 3. Regular bedtime, defined as the time the participant attempts to fall asleep, between
 22:00 hours and 01:00 hours, and regular waketime, defined as the time the participant
 gets out of bed for the day, between 05:00 hours and 09:00 hours

 4. Body mass index (BMI) ≥18 and <31 kg/m2 at Screening

 5. Subjective sleep onset latency (sSOL) <30 minutes and subjective wake after sleep
 onset (sWASO) <60 minutes on the Sleep Diary

 6. At least 3 years of experience driving at least 3000 km per year

 7. Holds a valid license to drive a vehicle in the European Union (EU) as confirmed at
 the Screening visit

 8. Has driving ability during the practice driving test that is judged to be adequate by
 the driving instructor

 9. Able to communicate adequately (written and verbal) in either Dutch or English as
 determined by the investigator

 Exclusion Criteria:

 1. A current complaint or diagnosis of insomnia disorder (per either The Diagnostic and
 Statistical Manual of Mental Disorders Version IV [DSM-IV] or Version 5 [DSM-5]
 criteria), sleep-related breathing disorder, periodic limb movement disorder, restless
 legs or narcolepsy, or an exclusionary score on a subscale of the SLEEP50

 2. Habitually naps more than 3 times per week

 3. Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a
 positive beta-human chorionic gonadotropin [B-hCG] test with a minimum sensitivity of
 25 IU/L or equivalent units of B-hCG). A separate baseline assessment is required if a
 negative screening pregnancy test was obtained more than 72 hours before the first
 dose of study drug.

 4. Females of childbearing potential who:

 -  Had unprotected sexual intercourse within 30 days before study entry and who do
 not agree to use a highly effective method of contraception (eg, total
 abstinence, an intrauterine device, a double-barrier method [such as condom plus
 diaphragm with spermicide], a contraceptive implant, an oral contraceptive, or
 have a vasectomized partner with confirmed azoospermia) throughout the entire
 study period or for 28 days after study drug discontinuation.

 -  Are currently abstinent, and do not agree to use a double-barrier method (as
 described above) or refrain from sexually active during the study period or for
 28 days after study drug discontinuation.

 -  Are using hormonal contraceptives but are not on a stable dose of the same
 hormonal contraceptive product for at least 4 weeks before dosing and who do not
 agree to use the same contraceptive during the study or for 28 days after study
 drug discontinuation. (NOTE: All females will be considered to be of childbearing
 potential unless they are postmenopausal [amenorrheic for at least 12 consecutive
 months, in the appropriate age group, and without other known or suspected cause]
 or have been sterilized surgically [ie, bilateral tubal ligation, total
 hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before
 dosing]).

 5. Males who have not had a successful vasectomy (confirmed azoospermia) or they and
 their female partners must meet the criteria above (ie, not of childbearing potential
 or practicing highly effective contraception throughout the study period or for 28
 days after study drug discontinuation). No sperm donation is allowed during the study
 period or for 28 days after study drug discontinuation.

 6. Clinically significant illness that requires medical treatment between Screening and
 Baseline

 7. Any clinically abnormal symptom or organ impairment found by medical history at
 Screening or Baseline and physical examinations, vital signs, ECG finding, or
 laboratory test results that require medical treatment

 8. Has a QT interval corrected using Fridericia's formula interval (QTcF interval) >450
 ms demonstrated on repeated ECGs (repeated only if initial ECG showed corrected QT
 interval (QTc) >450 ms) at Screening or Baseline

 9. Has a history of or a family history of congenital QT prolongation or with a history
 of risk factors for torsade de pointes (eg, heart failure, hypokalemia, family history
 of long QT syndrome), or uses concomitant medications that prolong the QT/QT interval
 corrected for heart rate (QTc interval)

 10. Has systolic blood pressure (BP) >140 mmHg (age 21-59) or >150 mmHg (age ≥60) or
 diastolic BP >90 mmHg (all ages) at Screening or Baseline

 11. Has a resting heart rate <50 or ≥100 beats/min at Screening or Baseline

 12. Has a history of drug or alcohol dependency or abuse (as defined by DSM-5 criteria)
 within approximately 2 years before Screening

 13. Any suicidal ideation with intent with or without a plan within 6 months of the
 Screening Period (ie, answering "Yes" to questions 4 or 5 on the Suicidal Ideation
 section of the C-SSRS)

 14. Habitually consumes more than 14 drinks per week (females) or more than 21 drinks per
 week (males)

 15. Has a positive alcohol breathalyzer test at Screening or Baseline check-in

 16. Smokes more than 6 cigarettes per day habitually and is unwilling to abstain from
 smoking cigarettes on evenings spent in the clinic until discharge after the driving
 test

 17. Habitually consumes more than 3 cups of caffeinated beverages per day

 18. Used any prohibited prescription or over-the-counter (OTC) concomitant medications
 within 1 week prior to starting the Sleep Diary during the Screening Period

 19. Transmeridian travel across more than 3 time zones in the 2 weeks before Screening, or
 between Screening and Baseline or plans for transmeridian travel across more than 3
 time zones during the study

 20. A positive urine drug test at Screening or unwilling to refrain from use of illegal
 recreational drugs or marijuana during the study

 21. Hypersensitivity to the study drug or any of the excipients or to zopiclone

 22. Participated (received investigational product) in another clinical trial less than 1
 month (or 5 elimination half-lives of the investigational product) before dosing or is
 currently enrolled in another clinical study