Lemborexant in Delayed Sleep Phase Syndrome (Eisai DSPS)

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, the investigators 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.

Study Overview

• Status: Recruiting
• Conditions: Delayed Sleep Phase Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: Lemborexant

Detailed Description

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 need 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. The prevalence of this condition is approximately 7-16% among adolescents and young adults.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Andrew D Krystal, MD, MS; Phone Number: 415-476-7702; Email: andrew.krystal@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94107
      • Recruiting
      • University of California San Francisco
      • Contact: Andrew D Krystal, MD MS; Phone Number: 415-476-7702; Email: andrew.krystal@ucsf.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

- Participants will be required to be 18 years of age or older and have delayed sleep phase syndrome (DSPS). Questionnaires will be used to identify potential confounders and to confirm a potential diagnosis of DSPS based on ICSD3 criteria: a) Sleep is delayed by two hours or more beyond what is considered an acceptable or conventional bedtime for the subject (their desired bedtime). b) Subjects not able to fall asleep if trying to sleep before the later bedtime; c) This is interfering with their wishes/having a 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, or any medical disorder/therapy that could interfere with the trial
• 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.
• 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, 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: Eisai Co., Ltd.; Stanford University
• Investigators: Principal Investigator: Andrew D Krystal, MD, MS, University of California, San Francisco

Publications and helpful links

General Publications

• Duffy JF, Dijk DJ, Hall EF, Czeisler CA. Relationship of endogenous circadian melatonin and temperature rhythms to self-reported preference for morning or evening activity in young and older people. J Investig Med. 1999 Mar;47(3):141-50.
• Micic G, Richardson C, Cain N, Reynolds C, Bartel K, Maddock B, Gradisar M. Readiness to change and commitment as predictors of therapy compliance in adolescents with Delayed Sleep-Wake Phase Disorder. Sleep Med. 2019 Mar;55:48-55. doi: 10.1016/j.sleep.2018.12.002. Epub 2018 Dec 14.
• Zeitzer JM, Joyce DS, McBean A, Quevedo YL, Hernandez B, Holty JE. Effect of Suvorexant vs Placebo on Total Daytime Sleep Hours in Shift Workers: A Randomized Clinical Trial. JAMA Netw Open. 2020 Jun 1;3(6):e206614. doi: 10.1001/jamanetworkopen.2020.6614.
• Zeitzer JM, Buckmaster CL, Lyons DM, Mignot E. Increasing length of wakefulness and modulation of hypocretin-1 in the wake-consolidated squirrel monkey. Am J Physiol Regul Integr Comp Physiol. 2007 Oct;293(4):R1736-42. doi: 10.1152/ajpregu.00460.2007. Epub 2007 Aug 8.
• Zhang S, Zeitzer JM, Yoshida Y, Wisor JP, Nishino S, Edgar DM, Mignot E. Lesions of the suprachiasmatic nucleus eliminate the daily rhythm of hypocretin-1 release. Sleep. 2004 Jun 15;27(4):619-27. doi: 10.1093/sleep/27.4.619.

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2023
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2027

Study Registration Dates

• First Submitted: March 7, 2025
• First Submitted That Met QC Criteria: March 7, 2025
• First Posted (Actual): March 13, 2025

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Lemborexant; Syndrome; Delayed Sleep Phase Syndrome
• Additional Relevant MeSH Terms: Nervous System Diseases; Mental Disorders; Pathologic Processes; Disease; Sleep Wake Disorders; Dyssomnias; Chronobiology Disorders; Occupational Diseases; Pathological Conditions, Signs and Symptoms; Syndrome; Sleep Disorders, Circadian Rhythm; Sleep Aids, Pharmaceutical; Orexin Receptor Antagonists; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Neurotransmitter Agents; Hypnotics and Sedatives; lemborexant
• Other Study ID Numbers: 23-38738

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data may be shared only with collaborators at Stanford University who are mirroring this study and recruiting half of the required participants and with Eisai Inc Ltd, the study sponsor that is providing the drug of investigation. Individuals will be assigned a unique coded identifier to limit risk of privacy loss
• IPD Sharing Time Frame: IPD from enrolled participants will be available to collaborators for the duration of the study (Mar 2023 - May 2027 (anticipated) until the study has ended.
• IPD Sharing Access Criteria: Collaborator Emmanuel Mignot from Stanford University and study sponsor Eisai will be able to access the data as participants from UCSF and Stanford will be combined for the overall data analyses
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No