Clinical trial NCT05594589: A Study to Assess the Pharmacodynamics of Lemborexant in Korean Participants With Insomnia Disorder
Official title: A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study to Assess the Pharmacodynamics of Lemborexant in Korean Subjects With Insomnia Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sleep Initiation and Maintenance Disorders
Keywords: Lemborexant
E2006
Dayvigo
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2022-10-26
Enrollment: 65
Sex: ALL
Minimum age (years): 19
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary purpose of the study is to evaluate the treatment difference between lemborexant 5 milligram (mg) (LEM5) and placebo (PBO) on latency to persistent sleep (LPS) using polysomnography (PSG) on Day 30.


Eligibility criteria: Inclusion Criteria:

1. Korean male or female, age 19 to 80 years, at the time of informed consent
2. Meets the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for Insomnia Disorder, as follows:

   * Complains of dissatisfaction with nighttime sleep, in the form of difficulty getting to sleep with or without difficulty staying asleep and/or awakening earlier in the morning than desired despite adequate opportunity for sleep
   * Frequency of complaint greater than or equal to (\>=) 3 times per week
   * Duration of complaint \>= 3 months
   * Associated with complaint of daytime impairment
3. Subjective Sleep Onset Latency (sSOL) typically \>= 30 minutes on at least 3 nights per week in the previous 4 weeks at Screening
4. Insomnia Severity Index (ISI) score \>=13 at Screening
5. Regular time in bed between 6.5 and 9.0 hours at Screening
6. At 2nd Screening Visit (Visit 2): Confirmation (via Sleep Diary) of a regular bedtime, defined as the time the participant attempts to sleep, between 21:00 and 24:00 on at least 5 of the final 7 nights and regular waketime, defined as the time the participant gets out of bed for the day, between 05:00 and 09:00 on at least 5 of the final 7 nights.
7. Confirmation of current insomnia symptoms, as determined from responses on the sleep diary on the 7 most recent mornings before the PSG during Screening Period (Visit 2), such that sSOL \>=30 minutes on at least 3 of the 7 nights
8. Confirmation of sufficient duration of time spent in bed, as determined from responses on the sleep diary on the 7 most recent mornings before the 2nd Screening Visit (Visit 2), such that there are no more than 2 nights with time spent in bed duration less than (\<) 7 hours or greater than (\>) 10 hours
9. During Run-in period, objective (PSG) evidence of insomnia as follows:

   * SE less than or equal to (\<=) 85 percent (%); and
   * LPS \>= 30 minutes
10. Provide written informed consent
11. Willing and able to comply with all aspects of the protocol, including staying in bed for at least 7 hours each night

Exclusion Criteria:

1. Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin (beta-hCG). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the 1st dose of study drug
2. Females of childbearing potential who:

   * Within 28 days before study entry, did not use a highly effective method of contraception, which includes any of the following:

     * total abstinence (if it is their preferred and usual lifestyle)
     * an intrauterine device or intrauterine hormone-releasing system (IUS)
     * a contraceptive implant
     * an oral contraceptive (Participant must have been on a stable dose of the same oral contraceptive product for at least 28 days before dosing and must agree to stay on the same dose of the oral contraceptive throughout the study and for 28 days after study drug discontinuation.)
     * have a vasectomized partner with confirmed azoospermia
   * Do not agree to use a highly effective method of contraception (as described above) throughout the entire study period and for 28 days after study drug discontinuation. It is permissible that if a highly effective method of contraception is not appropriate or acceptable to the participant, then the participant must agree to use a medically acceptable method of contraception, that is, double-barrier methods of contraception such as latex or synthetic condom plus diaphragm or cervical/vault cap with spermicide 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 (that is, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing)
3. Any history of a medical or psychiatric condition that in the opinion of the investigator(s) could affect the participants safety or interfere with the study assessments
4. A prolonged QT interval corrected for heart rate by Fridericia's formula (QTcF) interval (QTcF \>450 millisecond \[ms\]) as demonstrated by a repeated ECG. A history of risk factors for torsade de pointes (example, heart failure, hypokalemia, family history of long QT Syndrome) or the use of concomitant medications that prolonged the QTcF interval
5. Any suicidal ideation with intent with or without a plan at Screening or within 6 months of Screening
6. Any lifetime suicidal behavior
7. Evidence of clinically significant disease (example, cardiac; respiratory including chronic obstructive pulmonary disease, acute and/or severe respiratory depression; gastrointestinal; moderate and severe hepatic impairment; renal including severe renal impairment; neurological including myasthenia gravis; psychiatric disease; or malignancy within the past 5 years other than adequately treated basal cell carcinoma) or chronic pain that in the opinion of the investigator(s) could affect the participants safety or interfere with the study assessments. Participants for whom a sedating drug would be contraindicated for safety reasons because of the participants occupation or activities
8. Hypersensitivity to lemborexant or to their excipients
9. Scheduled for surgery during the study that requires general anesthesia or administration of prohibited medications
10. Known to be human immunodeficiency virus (HIV) positive
11. Active viral hepatitis (B or C) as demonstrated by positive serology
12. History of drug or alcohol dependency or abuse within approximately the last 2 years
13. A current diagnosis of sleep-related breathing disorder including obstructive sleep apnea (with or without continuous positive airway pressure \[CPAP\] treatment), periodic limb movement disorder, restless legs syndrome, circadian rhythm sleep disorder, or narcolepsy, or an exclusionary score on screening instruments to rule out individuals with symptoms of certain sleep disorders other than insomnia as follows:

    * STOPBang score \>=5
    * International Restless Legs Scale (IRLS) \>=16
14. Apnea-Hypopnea Index \>15 or Periodic Limb Movement with Arousal Index \>15 as measured on the PSG at the 2nd Screening Visit
15. Reports symptoms potentially related to narcolepsy, that in the clinical opinion of the investigator indicates the need for referral for a diagnostic evaluation for the presence of narcolepsy
16. Reports a history of sleep-related violent behavior, or sleep driving, or any other complex sleep-related behavior (example, making phone calls or preparing and eating food while sleeping)
17. For participants who underwent diagnostic PSG within 1 year before informed consent:

    * Age 19 to 64 years: Apnea hypopnea Index \>=10, or Periodic Limb Movements with Arousal Index \>=10,
    * Age \>=65 years: Apnea Hypopnea Index \>15, or Periodic Limb Movements with Arousal Index \>15
18. Beck Depression Inventory-II (BDI-II) score \>19 at Screening
19. Beck Anxiety Inventory (BAI) score \>15 at Screening
20. Habitually naps during the day more than 3 times per week
21. Excessive caffeine use that in the opinion of the investigator contributes to the participants insomnia, or habitually consumes caffeine containing beverages after 18:00 and is unwilling to forego caffeine after 18:00 for the duration of his/her participation in the study. Participants are excluded if, in the previous 3 months, they had symptoms that would meet DSM-5 criteria for caffeine intoxication, which includes consumption of a high dose of caffeine (significantly in excess of 250 mg) and \>=5 of the following symptoms: restlessness, nervousness, excitement, insomnia, flushed face, diuresis, gastrointestinal disturbance, muscle twitching, rambling flow of thought and speech, tachycardia or cardiac arrhythmia, periods of high energy, or psychomotor agitation. To be exclusionary, those symptoms must cause distress or impairment in social, occupational and other forms of functioning, and not be associated with other substance, mental disorder or medical condition
22. Reports habitually consuming more than 14 drinks containing alcohol per week (females) or more than 21 drinks containing alcohol per week (males), or unwilling to limit alcohol intake to no more than 2 drinks per day or forego having alcohol within the 3 hours before bedtime for the duration of his/her participation in the study
23. Comorbid nocturia that is causing or exacerbating the insomnia
24. Used any prohibited prescription or over-the-counter concomitant medications within 1 week or 5 half-lives, whichever is longer, before the 1st dose of study medication (Run-in Period)
25. Used any modality of treatment for insomnia, including cognitive behavioral therapy or marijuana within 1 week or 5 half-lives, whichever is longer, before the 1st dose of study medication (Run-in Period)
26. Failed treatment with dual orexin receptor antagonist drugs (efficacy and/or safety) following treatment with an appropriate dose and of adequate duration in the opinion of the investigator
27. Transmeridian travel across more than 3 time zones in the 2 weeks before Screening, or between Screening and Baseline, or plans to travel across different time zones during the study
28. Performed shift work in the 2 weeks before Screening, or between Screening and Baseline, or plans to do during the study
29. A positive drug test at Screening, Run-in, or Baseline, or unwilling to refrain from use of recreational drugs during the study
30. Currently enrolled in another clinical trial or used any investigational drug or device within 30 days or 5\* the half-life, whichever is longer, preceding informed consent
31. Previously participated in any clinical trial of lemborexant

Primary outcomes:
measure: Change From Baseline of LPS on Day 30 of LEM5 Treatment Compared to PBO
timeFrame: Baseline, Day 30
Secondary outcomes:
measure: Change From Baseline of LPS on Day 30 of LEM10 Treatment Compared to PBO
timeFrame: Baseline, Day 30
measure: Change From Baseline of Objective Sleep Efficiency (SE) on Day 30 of LEM5 Treatment Compared to PBO
timeFrame: Baseline, Day 30
measure: Change From Baseline of Objective SE on Day 30 of LEM10 Treatment Compared to PBO
timeFrame: Baseline, Day 30
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From start of study drug administration up to Day 58
measure: Number of Participants With Clinically Significant Abnormal Laboratory Parameters
timeFrame: From start of study drug administration up to Day 58
measure: Number of Participants With Clinically Significant Abnormal Vital Signs Values
timeFrame: From start of study drug administration up to Day 58
measure: Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) Findings
timeFrame: From start of study drug administration up to Day 58
measure: Plasma Concentrations of Lemborexant and its Metabolites (M4, M9, and M10)
timeFrame: Days 30 and 31: 0-1.5 hour
Other outcomes:
Locations:
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Suwon-si
country: Korea, Republic of
facility: The Catholic University of Korea, St. Vincent Hospital
state: Gyeonggi-do
city: Daegu-si
country: Korea, Republic of
facility: Keimyung University Dongsan Hospital
city: Incheon
country: Korea, Republic of
facility: Gacheon University Gil Medical Centre
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Konkuk University Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Hospital at Gangdong
Study officials:
References: