Long-term Study of Lemborexant in Insomnia Disorder (SUNRISE 2)

A Long-Term Multicenter, Randomized, Double-Blind, Controlled, Parallel Group Study of the Safety and Efficacy of Lemborexant in Subjects With Insomnia Disorder (SUNRISE 2)

The key objectives of this study are to determine, using sleep diaries, whether lemborexant at the doses 5 milligrams (mg) and 10 mg is superior to placebo on subjective sleep onset, subjective sleep efficiency, and subjective sleep maintenance in participants with insomnia disorder.

This is a long-term (approximately 1 year), multicenter, randomized, controlled, double-blind, parallel group study of two doses of lemborexant and placebo in approximately 900 male or female participants with insomnia disorder. Approximately 40% of participants will be age 65 years or older. The study will last a maximum of 60 weeks, and will include a Screening Period, an approximately 54-week Treatment Period (during which study medication will be administered), and a 2-week Follow-up Period. All participants will receive lemborexant for at least 6 months and will receive placebo at some point during the study. Participants will not know which medication they receive (lemborexant or placebo) until the study has been completed, and will not know the timings at which the medication will change.

Inclusion Criteria:

• Male or female, age 18 years or older at the time of informed consent

• Meets the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM 5) criteria for Insomnia Disorder, as follows:

  • Complains of dissatisfaction with nighttime sleep in the form of difficulty getting to sleep, 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

• History of (Subjective Sleep Onset Latency) sSOL ≥30 minutes on at least 3 nights per week in the previous 4 weeks and/or subjective Wake after Sleep Onset (sWASO) ≥60 minutes on at least 3 nights per week in the previous 4 weeks

• History of regular time spent in bed, either sleeping or trying to sleep, between 7 and 9 hours

• Regular bedtime, between 21:00 and 01:00 and regular wake time, the time the participant gets out of bed for the day, between 05:00 and 10:00

• Insomnia Severity Index (ISI) score ≥15

• Confirmation of current insomnia symptoms as determined from the Sleep Diary completed on at least 7 consecutive mornings (minimum 5 of 7 for eligibility), 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

• Confirmation of time spent in bed, as determined from on the Sleep Diary completed on 7 mornings between the first and second screening visit, such that there are not more than 2 nights with duration of time spent in bed 7 hours and 10 hours

• Confirmation of regular bedtimes and wake times such that the participant has a regular time spent in bed, either sleeping or trying to sleep, between 7 and 10 hours for the final 7 nights of the before visit 3.

• Confirmation of regular bedtime between 21:00 and 01:00 and time of getting out of bed for the day between 05:00 and 10:00 for the final 7 nights of the before visit 3.

• Willing and able to comply with all aspects of the protocol, including staying in bed for at least 7 hours each night

• Willing to not start a behavioral or other treatment program for insomnia during the participants participation in the study

Exclusion Criteria:

• A current diagnosis of sleep-related breathing disorder, 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.

  • STOPBang score greater than or equal to (>=) 5
  • International Restless Legs Scale (IRLS) score >=16
  • Epworth Sleepiness Scale (ESS) score >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

• 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 asleep

• For participants who underwent polysomnography (PSG) within the previous year:

  • 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

• Beck Depression Inventory - II (BDI II) score >19 at Screening

• Beck Anxiety Inventory (BAI) score >15 at Screening

• Habitually naps more than 3 times per week

• Females who are breastfeeding or pregnant at Screening or Study Baseline

• Females of childbearing potential who are not practicing acceptable pregnancy prevention methods (NOTE: All females will be considered to be of childbearing potential unless they are postmenopausal or have been sterilized surgically.)

• 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

• History of drug or alcohol dependency or abuse within approximately the previous 2 years

• 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

• A prolonged QT/QT interval corrected by Fridericia's formula (QTcF >450 ms) as demonstrated by a repeated electro cardiogram(ECG) at Screening (repeated only if initial ECG indicates a QTcF interval >450 ms)

• Current evidence of clinically significant disease (e.g., cardiac, respiratory, gastrointestinal, renal, neurological [including participants who lack capacity and/or whose cognitive decline indicates disorientation to person/place/time and/or situation], or psychiatric disease or malignancy other than 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

• Comorbid nocturia resulting in frequent need to get out of bed to use the bathroom during the night

• Scheduled for major surgery during the study

• Used any prohibited prescription or over-the-counter concomitant medications within 1 week before the first dose of study medication

• Used any modality of treatment for insomnia, including cognitive behavioral therapy or marijuana within 2 weeks before Screening

• 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

• Transmeridian travel across more than 3 time zones in the 2 weeks before Screening, or between Screening and Study Baseline

• Previously participated in any clinical trial of lemborexant