Lemborexant in Delayed Sleep Phase Syndrome

Study Overview
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Brief Summary
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The purpose of the study is to evaluate whether Lemborexant is more effective than placebo in shortening sleep onset latency in patients with delayed sleep phase syndrome (both type 1 and type 2). This will be tracked using sleep logs as well as actigraphy. In this 2-year study, we will examine if Lemborexant administered 5-10 mg nightly taken at desired bedtime (at least 2 hours prior to self-reported sleep onset habitual time) can improve the symptoms of Delayed Sleep Phase Syndrome.

Detailed Description
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Delayed sleep phase syndrome (DSPS) is a disorder in which a person's sleep is delayed by two hours or more beyond what is considered an acceptable or conventional bedtime. The delayed sleep then causes difficulty in being able to wake up at the desired time. In DSPS, bedtime is shifted later than the general population such that individuals have difficulty getting enough sleep to meet their sleep needs before they have to get up for their daytime obligations (work, school, childcare, etc.). As a result, patients experience daytime impairment, including daytime sleepiness and cognitive impairment. DSPS, if maintained in adulthood, is associated with numerous deleterious health effects, although causality is not well established. Two phenotypes of DSPS are recognized depending on the phase of entrainment: one with a late phase and normal phase angle (non-circadian) and other with a late phase and abnormal phase angle (circadian). The differentiation of these two phenotypes is theoretical: a mixed situation may be involved in some cases and the exact pathophysiology of each subtype is still controversial. In theory, however, separating the sample into these two subtypes is likely important to predict short- and long-term responses to orexin antagonists in DSPS. Lemborexant is one of the dual orexin receptor antagonists on the US market. The purpose of this study is to examine if lemborexant administered 5 to 10 mg nightly, taken at desired bedtime (at least 2 hours prior to self-reported sleep onset time), can improve the symptoms of Delayed Sleep Phase Syndrome both in the circadian and non-circadian phenotypes. The phenotypes will be recruited in 1:1 proportion.The effect of lemborexant will be analyzed based on the collection of information from actigraphy watches, sleep diaries, and sleep scales. The total participation time involved in this study will be approximately 6 weeks (2 weeks of baseline assessment followed by 2-weeks of treatment/placebo, and 2 weeks post-treatment).

Official Title
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Lemborexant in Delayed Sleep Phase Syndrome

Conditions
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Delayed Sleep Phase Syndrome

Intervention / Treatment
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* Drug: Lemborexant
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older. Diagnosed with delayed sleep phase syndrome (DSPS) meaning that: Sleep is delayed by two hours or more beyond what is considered an acceptable or conventional bedtime for the subject (their desired bedtime). Subjects not able to fall asleep if trying to sleep before the later bedtime; This is interfering with their wishes/having social impact. Concomitant medications will be allowed, though dosages will be required to remain fixed throughout participation in the study. The participant also needs to be willing and able to comply with all aspects of the protocol. Exclusion Criteria: Clinically significant depression (PHQ-9 score of 10 or more), anxiety disorder (GAD-7 score of 10 or more), substance use disorder, any other sleep disorder (assessed by the Alliance Sleep Questionnaire- ASQ), or any medical disorder/therapy that could interfere with the trial (this will be verified through interview and analysis of the ASQ). Use of medications with significant effects on sleep-wake function (insomnia therapies, stimulants)- unless they are discontinued at least 5 half-lives prior to study participation. Non-sedative antidepressants or SSRI will be allowed if at a stable dose in the absence of concomitant severe depression or severe anxiety. Use of CYP3A inhibitors and CYP3A inducers, at least 1 week (or five half-lives, whichever is longer) prior to the first day of the baseline phase. Pregnancy (verified by urine pregnancy test on visits 1, 2, and 3) or plan to become pregnant in the next 3 months or currently breastfeeding. Shift workers or subjects working unusual hours. Any risk of suicide within 6 months of screening period or throughout the trial (accessed by the Investigator and by the C-SSRS questionnaire). Transmeridian travel across more than 3 time zones 4 weeks prior to the screening phase. Transmeridian travel across more than 2 time zones during this trial (including the screening phase). Having a positive drug test or being unwilling to refrain from using illegal drugs or marijuana during this trial. Any clinically abnormal symptom or organ impairment found by medical history at Screening or Baseline and physical examinations, vital signs, ECG findings, or laboratory test results that require medical treatment. Impaired liver function (values for enzymes aspartate transaminase (AST) and alanine transaminase (ALT) > 1.5 times the Upper Limit of Normal). Known to be human immunodeficiency virus positive. Has a QT interval corrected using Fridericia's formula interval (QTcF interval) >450 ms demonstrated on repeated ECGs (repeated only if initial ECG showed corrected QT interval (QTc) >450 ms) at Screening or Baseline.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lemborexant<br>Patients receive Lemborexant 5mg for 7 days and may be dose adjusted to 10mg. Patients continue to take Lemborexant 5mg or 10 mg for an additional 7 days. | Drug: Lemborexant<br>* Lemborexant tablet administered orally once daily.<br>* Other names: dayvigo®;|
| Placebo Comparator: Placebo<br>Patients receive placebo to match Lemborexant for 14 days. | Drug: Placebo<br>* Placebo to match Lemborexant tablet administered orally once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in actigraphy sleep latency onset | Sleep latency is the time from laying down until falling asleep. Actigraphy data obtained using Axivity- AX6. | From 2 weeks prior to randomization to 4 weeks post randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Epworth Sleepiness Scale (ESS) | This is a scale to evaluate daytime sleepiness. Range from 0 to 24 points (higher scores mean more sleepiness). | From randomization to 4 weeks post randomization | 
| Change in Karolinska Sleepiness Scale (KSS) | Self-report for daytime sleepiness with 1 being extremely alert and 10 being extremely sleepy, can't keep awake. | From randomization to 4 weeks post randomization | 
| Change in sleep diary derived sleep onset latency | Sleep latency is the time from laying down until falling asleep as estimated by patient in dairy. | From 2 weeks prior to randomization to 4 weeks post randomization | 
| Sleep Regularity Index | Sleep Regularity Index is defined as the percentage probability of a person being asleep (or awake) at any two time points 24 hours apart. Actigraphy data obtained using Axivity- AX6. | From 2 weeks prior to randomization to 4 weeks post randomization | 
| Change in actigraphy derived total sleep time | Actigraphy data obtained using Axivity- AX6. | From 2 weeks prior to randomization to 4 weeks post randomization | 
| Change in sleep diary derived total sleep time. | Estimated by patient in dairy. | From 2 weeks prior to randomization to 4 weeks post randomization | 
| Change in mean actigraphy derived wake time | Wake time is total time awake over night after sleep onset. Actigraphy data obtained using Axivity- AX6. | From 2 weeks prior to randomization to 4 weeks post randomization | 
| Change in mean sleep diary derived wake time | Wake time is total time awake over night after sleep onset as estimated by patient in dairy. | From 2 weeks prior to randomization to 4 weeks post randomization |