A Study to Evaluate Next-Dose Transition From Zolpidem to Lemborexant (LEM) for the Treatment of Insomnia
Condition: Insomnia
MeSH terms: Sleep Initiation and Maintenance Disorders
Intervention: LEM 5 mg; LEM 10 mg
Intervention description: LEM tablet.; LEM tablet.
Intervention MeSH terms: Lemborexant
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 53.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Insomnia; Sleep Initiation and Maintenance Disorders; Insomnia Disorder; Sleeplessness; E2006; Zolpidem; Lemborexant

Summary:

      The primary objective of the study is to evaluate the proportion of adult [greater than or
      equal to (>=) 18 years] participants with insomnia disorder taking zolpidem tartrate
      immediate release (ZOL-IR) or zolpidem tartrate extended release (ZOL-ER), intermittently or
      frequently, who transition to lemborexant 5 milligram (mg) (LEM5) or 10 mg (LEM10) after 2
      weeks of receiving LEM.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Meets the Diagnostic and Statistical Manual of Mental Disorders, 5th ed (DSM-5)
             criteria for Insomnia Disorder, either currently or prior to zolpidem use, 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

               -  Frequency of complaint >=3 times per week

               -  Duration of complaint >=3 months

               -  Associated with complaint of daytime impairment

          2. Reports spending at least 7 hours in bed per night

          3. History of intermittent [taking zolpidem at least 3 or 4 nights per week], or frequent
             use (at least 5 nights per week) of ZOL-IR or ZOL-ER, for at least 1 month

          4. Confirmation of intermittent or frequent use of zolpidem (based on review of drug use
             data). Intermittent use is defined as taking zolpidem at least 3 but fewer than 5
             nights per week, for at least 2 weeks each of the 3-week Screening Period. Frequent
             use is defined as taking zolpidem at least 5 nights per week, during, at minimum, the
             last 2 weeks of the 3-week Screening Period

          5. Willing and able to comply with all aspects of the protocol, including staying in bed
             for at least 7 hours each night

          6. Willing not to start another pharmacologic treatment for the management of insomnia
             during the participant's participation in the study

        Exclusion Criteria:

          1. Females who are breastfeeding or pregnant at screening or baseline (as documented by a
             positive serum pregnancy 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 (IUS)

               -  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 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)

          3. Any history of moderate or severe obstructive sleep apnea (OSA)

          4. Current evidence of a clinically significant, active respiratory disorder other than
             mild OSA. This includes bronchiectasis, emphysema, asthma, chronic obstructive
             pulmonary disease or any other pulmonary disorder identified by review of medical
             history or physical examination, and which in the opinion of the investigator, could
             compromise the participant's safety or interfere with study assessments

          5. A current diagnosis of periodic limb movement disorder, restless legs syndrome,
             circadian rhythm sleep disorder, or an exclusionary score on screening instruments to
             rule out individuals with symptoms of certain sleep disorders other than insomnia as
             follows:

               -  STOP-Bang score >=5 (participants previously diagnosed with mild OSA are not
                  excluded)

               -  International Restless Legs Scale (IRLS) score >=16

          6. Habitually naps during the day more than 3 times per week

          7. 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

          8. Reports a history of sleep-related violent behavior, or sleep driving, or any other
             complex sleep-related behavior (eg, making phone calls or preparing and eating food
             while sleeping), whether spontaneous or associated with a pharmacological sleep agent

          9. Takes a dose of ZOL-IR greater (>)10 mg per night, or ZOL-ER >12.5 mg per night

         10. Takes a dose of zolpidem that is lower than what is prescribed

         11. Reports having altered zolpidem tablets

         12. Unwilling to forgo alcohol consumption within 3 hours of bedtime for the duration of
             participation in the study

         13. 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
             (A list of prohibited concomitant medications is presented in the protocol)

         14. Used any pharmacologic modality of treatment for insomnia other than zolpidem,
             including marijuana, within 1-week or 5 half-lives, whichever is longer, before the
             Screening Period

         15. A prolonged difference between QTc corrected by Fridericia's formulas (QTcF) interval
             [QTcF >450 millisecond (ms)] as demonstrated by a repeated electrocardiogram

         16. Any suicidal ideation with intent with or without a plan at Screening or within 6
             months of Screening (ie, answering "Yes" to questions 4 or 5 on the Suicidal Ideation
             section of the Columbia-Suicide Severity Rating Scale [C-SSRS])

         17. Any lifetime suicidal behavior (per the Suicidal Behavior section of the C-SSRS)

         18. Evidence of clinically significant disease (eg, cardiac, respiratory,
             gastrointestinal, and renal disease) 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

         19. Hypersensitivity to LEM or any of the excipients

         20. Any history of or concomitant medical condition that in the opinion of the
             investigator(s) would compromise the participant's ability to safely complete the
             study

         21. Planned surgery that requires general, spinal, or epidural anesthesia that would take
             place during the study. Planned surgery, which requires only local anesthesia and
             which can be undertaken as a day case without inpatient stay postoperatively, need not
             result in exclusion if in the opinion of the investigator this operation does not
             interfere with the study procedures and patient safety

         22. Psychotic disorder(s) or unstable recurrent affective disorder(s) evident by use of
             antipsychotics or prior suicide attempt(s) within approximately the last 2 years

         23. History of drug or alcohol dependency or abuse within approximately the last 2 years

         24. Currently enrolled in another clinical study or used any investigational drug or
             device within 28 days or 5 times the half-life, whichever is longer, preceding
             informed consent

         25. Previously participated in any clinical trial of LEM