Study of the Efficacy and Safety of Lemborexant in Subjects 55 Years and Older With Insomnia Disorder (SUNRISE 1)
Condition: Insomnia
MeSH terms: Sleep Initiation and Maintenance Disorders
Intervention: Lemborexant; Lemborexant; Lemborexant-matched placebo; Zolpidem tartrate; Zolpidem-matched placebo
Intervention description: Lemborexant 5 mg will be administered orally in tablet form at home each night, immediately before the time the participant intends to try to sleep.; Lemborexant 10 mg will be administered orally in tablet form at home each night, immediately before the time the participant intends to try to sleep.; Lemborexant-matched placebo be administered orally in tablet form at home each night, immediately before the time the participant intends to try to sleep.; Zolpidem tartrate extended release 6.25 mg will be administered orally in tablet form at home each night, immediately before the time the participant intends to try to sleep.; Zolpidem-matched placebo will be administered orally in tablet form at home each night, immediately before the time the participant intends to try to sleep.
Intervention MeSH terms: Zolpidem; Lemborexant
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 1006.0
Sex: All
Minimum age: 55 Years
Healthy volunteers: No
Keywords: E2006; Lemborexant; zolpidem tartrate; Ambien CR; Insomnia

Summary:

      This study will be conducted to demonstrate, using polysomnography, that lemborexant 10
      milligrams (mg) and 5 mg is superior to placebo on objective sleep onset as assessed by
      latency to persistent to sleep (LPS) after the last 2 nights of 1 month of treatment in
      participants 55 years and older with insomnia disorder.
    

Eligibility criteria:

        Inclusion Criteria

          1. Male age 65 years or older or female age 55 years or older at the time of informed
             consent

          2. Meets the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition
             criteria for Insomnia Disorder, as follows:

               -  Complains of dissatisfaction with nighttime sleep, in the form of difficulty
                  staying asleep and/or awakening earlier in the morning than desired despite
                  adequate opportunity for sleep (Note that if the complaint is limited to
                  difficulty initiating sleep, the participant is not eligible)

               -  Frequency of complaint ≥ 3 times per week

               -  Duration of complaint ≥ 3 months

               -  Associated with complaint of daytime impairment

          3. History of subjective wake after sleep onset (sWASO) typically ≥ 60 minutes on at
             least 3 nights per week in the previous 4 weeks

          4. Reports regular time spent in bed, either sleeping or trying to sleep, between 7 and 9
             hours

          5. Reports habitual bedtime, defined as the time the participant attempts to sleep,
             between 21:00 and 24:00 and habitual waketime between 05:00 and 09:00

          6. Insomnia Severity Index (ISI) score ≥ 13

          7. Confirmation of current insomnia symptoms as determined from responses on the Sleep
             Diary before the second screening visit

          8. Confirmation of regular bedtime and waketime as determined from responses on the Sleep
             Diary

          9. Confirmation of sufficient duration of time spent in bed, as determined from responses
             on the Sleep Diary

         10. Objective (polysomnography [PSG]) evidence of insomnia as follows:

             a) Wake after sleep onset (WASO) average ≥ 60 minutes on the 2 consecutive PSGs, with
             neither night < 45 minutes

         11. Willing and able to comply with all aspects of the protocol, including staying in bed
             for at least 7 hours each night

         12. 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

          1. 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:

               1. STOPBang score ≥5

               2. International Restless Legs Scale score ≥16

               3. Epworth Sleepiness Scale score >15 (scores of 11 to 15 require excessive daytime
                  sleepiness to be recorded in participant's Medical History)

          2. 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

          3. On the Munich Parasomnia Scale (MUPS), endorsed the item that corresponds to a history
             of sleep-eating or reports a history of sleep-related violent behavior, sleep-driving,
             or symptoms of another parasomnia that in the investigator's opinion make the
             participant unsuitable for the study

          4. Apnea-Hypopnea Index > 15 or Periodic Limb Movement with Arousal Index >15 as measured
             on the PSG at the second screening visit

          5. Beck Depression Inventory - II (BDI-II) score >19 at Screening

          6. Beck Anxiety Index (BAI) score >15 at Screening

          7. Habitually naps during the day more than 3 times per week

          8. Is a female of childbearing potential Note: All females will be considered to be of
             childbearing potential unless they are postmenopausal (defined as amenorrheic for at
             least 12 consecutive months, and are postmenopausal without other known or suspected
             cause), or have been sterilized surgically (i.e., bilateral tubal ligation, total
             hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before
             dosing).

          9. 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.

         10. History of drug or alcohol dependency or abuse within approximately the previous 2
             years

         11. 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

         12. Known to be positive for human immunodeficiency virus

         13. Active viral hepatitis (B or C) as demonstrated by positive serology at Screening

         14. A prolonged QT/QTcF interval (QTcF >450 milliseconds [ms]) as demonstrated by a
             repeated electrocardiogram (ECG) at Screening (repeated only if initial ECG indicates
             a QTcF interval >450 ms)

         15. Current evidence of clinically significant disease (e.g., cardiac; respiratory
             including chronic obstructive pulmonary disease, acute and/or severe respiratory
             depression; gastrointestinal; 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, including the ability to
             perform tasks on the cognitive performance assessment battery (PAB). Participants for
             whom a sedating drug would be contraindicated for safety reasons because of the
             participant's occupation or activities are also excluded.

         16. Comorbid nocturia resulting in frequent need to get out of bed to use the bathroom
             during the night

         17. 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
             assessment, including the ability to perform the PAB.

         18. Any suicidal ideation with intent with or without a plan, at the time of or within 6
             months before the electronic Columbia-Suicide Severity Rating Scale (eC-SSRS)
             administration during the Prerandomization Phase (i.e., answering "Yes" to questions 4
             or 5 on the Suicidal Ideation section of the eC-SSRS)

         19. Any suicidal behavior in the past 10 years (per the Suicidal Behavior section of the
             eC-SSRS)

         20. Scheduled for surgery during the study

         21. 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).

         22. 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)

         23. Failed treatment with suvorexant (Belsomra®) (efficacy and/or safety) following
             treatment with an appropriate dose and of adequate duration in the opinion of the
             investigator

         24. 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

         25. A positive drug test at Screening, Run-In, or Baseline, or unwilling to refrain from
             use of recreational drugs during the study

         26. Hypersensitivity to lemborexant or zolpidem or to their excipients

         27. 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

         28. Previously participated in any clinical trial of lemborexant