Clinical trial NCT04549168: A Study of Lemborexant in Chinese Participants With Insomnia Disorder
Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 3 Study of the Efficacy and Safety of Lemborexant in Chinese Subjects With Insomnia Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Sleep Initiation and Maintenance Disorders
Keywords: Insomnia disorder
Lemborexant
Chinese Participants
E2006
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2020-09-16
Enrollment: 194
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study is to confirm using polysomnography (PSG) that lemborexant 10 milligram (mg) is superior to placebo on objective sleep onset as assessed by latency to persistent sleep (LPS) during the last 2 nights of 1 month of treatment in participants with insomnia disorder.

Detailed description: The study will have 2 phases: the Prerandomization Phase and the Randomization Phase. The Prerandomization Phase will comprise 3 periods that will last up to a maximum of 35 days: a Screening Period, a Run-in Period, and a Baseline Period. The Randomization Phase will comprise a Treatment Period during which participants will be treated for 30 nights (1 month) and a minimum 14-day Follow-up Period before an End of Study (EOS) Visit (up to 54 days). The total study duration for each participant on this study is 89 days.

Eligibility criteria: Inclusion Criteria:

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

1. Chinese male or female, age 18 years or older, at the time of informed consent (in Taiwan only participants with age 20 years or older are eligible)
2. Meets the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for Insomnia Disorder, as follows:

   * Complains of dissatisfaction with night time sleep, in the form of 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. At Screening: History of sSOL \>=30 minutes on at least 3 nights per week in the previous 4 weeks and/or sWASO \>=60 minutes on at least 3 nights per week in the previous 4 weeks
4. At Screening: Reports regular time spent in bed, either sleeping or trying to sleep, between 7 and 9 hours
5. At second Screening Visit (Visit 2a) and Run-in Visit (Visit 3a): Sleep diary confirms regular bedtime, defined as the time the participant attempts to sleep, between 21:00 and 01:00 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 10:00 on at least 5 of the final 7 nights
6. At Screening and Baseline: ISI score \>=15
7. Confirmation of current insomnia symptoms, as determined from responses on the sleep diary on the 7 most recent mornings before the first PSG during Screening Period (Visit 2a) and Run-in visit (Visit 3a), such that sSOL \>=30 minutes on at least 3 of the 7 nights and/or sWASO \>=60 minutes on at least 3 of the 7 nights
8. At the second Screening Visit (Visit 2a) and the Run-in visit (Visit 3a): 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 Visit, 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 the Run-in Period, objective (PSG) evidence of insomnia as follows:

   1. LPS average \>=30 minutes on the 2 consecutive Baseline PSGs, with neither night \<20 minutes and/or
   2. WASO average \>=60 minutes on the two consecutive Baseline PSGs, with neither night \<45 minutes
10. Willing and able to comply with all aspects of the protocol, including staying in bed for at least 7 hours each night
11. Willing not to start a behavioral or other treatment program for the treatment of insomnia during the participant's participation in the study

Exclusion Criteria:

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

1. Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin test). 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
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
   * a contraceptive implant
   * an oral contraceptive (participant must be on a stable dose of the same oral contraceptive product for at least 28 days before dosing and 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 participant's safety or interfere with the study assessments
4. A prolonged corrected QT interval by Fredericia's formula (QTcF) interval (QTcF \>450 millisecond \[ms\]) as demonstrated by a repeated electrocardiogram. A history of risk factors for torsade de pointes (for 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 suicidal behavior in the past 10 years
7. Evidence of clinically significant disease (for 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 participant's safety or interfere with the study assessments. Participants for whom a sedating drug would be contraindicated for safety reasons because of the participant's occupation or activities are also excluded
8. Hypersensitivity to lemborexant or to their excipients
9. Scheduled for surgery during the study
10. Known to be human immunodeficiency virus 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 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:

    * Snoring, Tiredness, Observed apnea, high blood Pressure (STOP)-Body mass index (BMI), Age, Neck circumference, and Gender (BANG) score \>=5
    * International Restless Legs Scale score \>=16
14. Apnea-hypopnea Index \>15 or Periodic Limb Movement with Arousal Index \>15 as measured on the PSG at the second 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 (for 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 18 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 score \>19 at Screening
19. Beck Anxiety Inventory 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 participant's 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. Excluding 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 first 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 first 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 more than 3 time zones during the study (China mainland will be considered as 1 time zone)
28. A positive drug test at Screening, Run-in, or Baseline, or unwilling to refrain from use of recreational drugs during the study
29. Currently enrolled in another clinical trial or used any investigational drug or device within 30 days or 5 half-lives, whichever is longer preceding informed consent
30. Previously participated in any clinical trial of lemborexant

Primary outcomes:
measure: Change From Baseline of Mean Latency to Persistent Sleep (LPS) Over the Last 2 Nights of 1 Month of Treatment of Lemborexant 10 mg Compared to Placebo
timeFrame: Baseline, Days 29 and 30
Secondary outcomes:
measure: Change From Baseline of Mean Objective Sleep Efficiency (SE) Over the Last 2 Nights of 1 Month Treatment of Lemborexant 10 mg Compared to Placebo
timeFrame: Baseline, Days 29 and 30
measure: Change From Baseline in Mean Objective Wake After Sleep Onset (WASO) Over the Last 2 Nights of 1 Month Treatment of Lemborexant 10 mg Compared to Placebo
timeFrame: Baseline, Days 29 and 30
measure: Change From Baseline of Subjective Sleep Onset Latency (sSOL) Over the Last 7 Nights of 1 Month Treatment of Lemborexant 10 mg Compared to Placebo
timeFrame: Baseline, Nights 24 to 30
measure: Change From Baseline of Subjective Sleep Efficiency (sSE) Over the Last 7 Nights of 1 Month of Treatment of Lemborexant 10 mg Compared to Placebo
timeFrame: Baseline, Nights 24 to 30
measure: Change From Baseline in Subjective Wake After Sleep Onset Over the Last 7 Nights of 1 Month Treatment of Lemborexant 10 mg Compared to Placebo
timeFrame: Baseline, Nights 24 to 30
measure: Change From Baseline of Mean Latency to Persistent Sleep Over the First 2 Nights of 1 Month of Treatment of Lemborexant 10 mg Compared to Placebo
timeFrame: Baseline, Nights 1 and 2
measure: Change From Baseline of Mean Sleep Efficiency Over the First 2 Nights of 1 Month of Treatment of Lemborexant 10 mg Compared to Placebo
timeFrame: Baseline, Nights 1 and 2
measure: Change From Baseline of Mean Wake After Sleep Onset Over the First 2 Nights of 1 Month of Treatment of Lemborexant 10 mg Compared to Placebo
timeFrame: Baseline, Nights 1 and 2
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: From the first dose of study drug up to 44 days
measure: Change From Baseline in Insomnia Severity Index (ISI) Total Score After 1 Month of Treatment With Lemborexant 10 mg Compared to Placebo
timeFrame: Baseline to Day 31
measure: Change From Baseline in Insomnia Severity Index Daytime Functioning Score After 1 Month of Treatment With Lemborexant 10 mg Compared to Placebo
timeFrame: Baseline to Day 31
measure: Number of Participants With Rebound Insomnia on Average of First 3 Nights (Nights 31 to 33), Average of First 7 Nights (Nights 31 to 37), and Average of Last 7 Nights (Nights 38 to 44) During the Follow-up Period
timeFrame: First 3 nights (Nights 31 to 33), First 7 nights (Nights 31 to 37) and Last 7 nights (Nights 38 to 44) of Follow up Period
measure: Change From Baseline in Mean Morning Residual Sleepiness Score Evaluated During Treatment and Follow-up Periods
timeFrame: Baseline, First 7 mornings (Mornings 1 to 7) and Last 7 mornings (Mornings 24 to 30) of Treatment period; First 7 mornings (Mornings 31 to 37) and Last 7 mornings (Mornings 38 to 44) of Follow-up period
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tiantan Hosptial, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Peking University Sixth Hospital
state: Beijing
city: Beijing
country: China
facility: Xuanwu Hospital Capital Medical University
state: Beijing
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital of Southern Medical University
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Jinan University
state: Guangdong
city: Shijiazhuang
country: China
facility: The First Hospital of Hebei Medical University
state: Hebei
city: Shijiazhuang
country: China
facility: The Third Hospital of Hebei Medical University
state: Hebei
city: Xinxiang
country: China
facility: Henan Mental Health Center
state: Henan
city: Wuhan
country: China
facility: Wuhan Mental Health Center
state: Hubei
city: Nanjing
country: China
facility: Nanjing Brain Hosptial
state: Jiangsu
city: Suzhou
country: China
facility: The Second Affiliated Hospital of Soochow University
state: Jiangsu
city: Nanchang
country: China
facility: The Second Affiliated Hospital of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: Jilin First University Affiliated Hospital
state: Jilin
city: Hohhot
country: China
facility: Inner Mongolia Autonomous Region Peoples Hospital
state: Mongolia
city: Xian
country: China
facility: Tangdu Hospital
state: Shaanxi
city: Jinan
country: China
facility: Shandong Provincial Qianfushan Hospital
state: Shandong
city: Shanghai
country: China
facility: Huashan Hospital Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Mental Health Center
state: Shanghai
city: Taiyuan
country: China
facility: First Hospital of Shanxi Medical University
state: Shannxi
city: Tianjin
country: China
facility: Tianjin Anding Hospital
state: Tianjin
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation Linkou Chang Gung Memorial Hospital
state: Taipei
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
References: