Lemborexant for Delayed Sleep Phase Syndrome

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Stanford University

Must not be taking: Insomnia therapies, Stimulants, CYP3A drugs

Disqualifiers: Depression, Anxiety, Substance use, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 2 weeks

60 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

You can continue taking your current medications, but the dosages must stay the same during the study. However, if you are using medications that affect sleep-wake function, you may need to stop them before joining the trial. Please check with the study team for specific guidance.

Is lemborexant safe for humans?

Lemborexant has been studied in several clinical trials for insomnia and is generally considered safe, with common side effects similar to those of a placebo, such as sleepiness and mild infections. It does not cause significant next-day drowsiness, and its safety profile is consistent across different doses. ^{1 2 3 4 5}

How does the drug lemborexant differ from other treatments for Delayed Sleep Phase Syndrome?

Lemborexant is unique because it works by blocking orexin receptors, which are involved in wakefulness, helping to regulate sleep patterns. This mechanism is different from other sleep aids that often target different pathways, such as those affecting the neurotransmitter GABA (gamma-aminobutyric acid). ^{1 3 6 7 8}

Research Team

Emmanuel Mignot, MD

Principal Investigator

Stanford University

Eligibility Criteria

Adults diagnosed with Delayed Sleep Phase Syndrome (DSPS), where sleep is delayed by two hours or more beyond their desired bedtime, causing social impact. Participants must be willing to comply with the study protocol and keep medication dosages fixed throughout the trial. Exclusions include drug use, significant effects on sleep from other medications, certain medical conditions including depression and anxiety disorders, pregnancy, unusual work hours, recent transmeridian travel, and impaired liver function.

Inclusion Criteria

The participant also needs to be willing and able to comply with all aspects of the protocol

My condition is affecting my daily life and social interactions.

I can't fall asleep if I try to sleep before my usual bedtime.

Exclusion Criteria

I have no symptoms or test results that need medical treatment.

Shift workers or subjects working unusual hours

My liver enzymes are higher than normal.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Baseline Assessment

Participants undergo baseline assessment to collect initial sleep data

2 weeks

Daily sleep logs and actigraphy

Treatment

Participants receive Lemborexant or placebo for 2 weeks to evaluate its effect on sleep onset latency

2 weeks

Daily sleep logs and actigraphy

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Daily sleep logs and actigraphy

Treatment Details

Interventions

• Lemborexant
• Placebo

Trial Overview The trial tests if Lemborexant (5-10 mg nightly) helps people with DSPS fall asleep faster compared to a placebo. Over two years, participants will take the drug at least 2 hours before their habitual sleep onset time. Effectiveness will be measured using sleep logs and actigraphy—a method that tracks movement to assess sleep patterns.

Participant Groups

Group I: Lemborexant Active Control 1 Intervention

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.

Group II: Placebo Placebo Group 1 Intervention

Patients receive placebo to match Lemborexant for 14 days.

Lemborexant is already approved in United States, Canada, Japan for the following indications:

Approved in United States as Dayvigo for:

• Insomnia characterized by difficulties with sleep onset and/or sleep maintenance in adults

Approved in Canada as Dayvigo for:

• Insomnia characterized by difficulties with sleep onset and/or sleep maintenance, with or without associated impairment in daily functioning

Approved in Japan as Dayvigo for:

• Treatment of insomnia

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

University of California, San Francisco

Collaborator

Trials

2,636

Recruited

19,080,000+

Findings from Research

Lemborexant is a dual orexin receptor antagonist approved in December 2019 for treating insomnia in adults, effectively helping with both sleep onset and maintenance.

In addition to its use for insomnia, lemborexant is being studied for treating irregular sleep-wake rhythm disorder in patients with mild to moderate Alzheimer's disease, indicating its potential broader applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lemborexant: First Approval. Scott, LJ.[2021]

Lemborexant has been shown to significantly reduce the time it takes to fall asleep compared to placebo and is also effective when compared to the active control zolpidem ER, based on two phase 3 trials.

The medication is generally well-tolerated, with fewer severe side effects like cognitive impairment and complex sleep-related behaviors compared to traditional insomnia treatments, making it a suitable option, especially for older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of the Efficacy and Safety of Lemborexant, a Dual Receptor Orexin Antagonist (DORA), in the Treatment of Adults With Insomnia Disorder. Waters, K.[2022]

In a phase 3 trial involving 321 subjects, those who initially received placebo for 6 months showed improvements in sleep outcomes, but further enhancements were observed when switched to lemborexant (LEM) treatment, particularly in sleep onset latency and total sleep time.

Among participants who did not respond to placebo, 11%-15% experienced positive effects from lemborexant after switching, indicating that lemborexant can provide additional benefits even after prior treatment with placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of lemborexant in subjects previously treated with placebo for 6 months in a randomized phase 3 study. Yardley, J., Inoue, Y., Pinner, K., et al.[2023]

Lemborexant, a dual orexin receptor antagonist for insomnia, showed no significant next-day impairment in postural stability or driving performance compared to placebo, indicating its safety for next-day functioning.

While mild to moderate somnolence was the most common side effect, it rarely led to discontinuation of the drug, suggesting lemborexant is generally well-tolerated in both healthy individuals and those with insomnia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of residual morning effects of lemborexant treatment for insomnia: summary of findings across 9 clinical trials. Moline, M., Zammit, G., Yardley, J., et al.[2021]

Lemborexant, an orexin receptor antagonist approved for insomnia, was studied in a large population of 1,892 subjects, showing that its pharmacokinetics are influenced by factors like body mass index and age, particularly in older adults.

The incidence of treatment-emergent adverse events (TEAEs) with lemborexant was low (3% to 8%) and similar to placebo, indicating that it can be safely administered without requiring dose adjustments based on patient characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics and Exposure-Response Analyses for the Most Frequent Adverse Events Following Treatment With Lemborexant, an Orexin Receptor Antagonist, in Subjects With Insomnia Disorder. Lalovic, B., Majid, O., Aluri, J., et al.[2021]

Lemborexant (LEM) significantly improved subjective sleep outcomes, such as sleep onset latency and sleep efficiency, in 178 Asian subjects with insomnia over a 12-month period, showing sustained benefits beyond the initial 6 months compared to placebo.

The treatment was well-tolerated, with most treatment-emergent adverse events being mild to moderate, indicating a favorable safety profile for LEM in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of lemborexant over 12 months in Asian adults with insomnia disorder. Dash, A., Pinner, K., Inoue, Y., et al.[2022]

Lemborexant, a dual orexin receptor antagonist, demonstrated significant and sustained improvements in sleep onset and maintenance over twelve months in a study involving 949 participants, with benefits maintained from the initial six months of treatment.

The treatment was generally safe, with most adverse events being mild to moderate, and there was no evidence of rebound insomnia or withdrawal symptoms after discontinuation, indicating its potential for long-term use in managing insomnia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effectiveness and safety of lemborexant in adults with insomnia disorder: results from a phase 3 randomized clinical trial. Yardley, J., Kärppä, M., Inoue, Y., et al.[2021]

In a study involving 291 adults with insomnia, lemborexant doses of 2.5 to 10 mg significantly improved sleep efficiency and reduced sleep onset latency compared to placebo, while minimizing next-morning sleepiness.

The 15 mg dose of lemborexant was particularly effective, leading to early success in the trial, and was associated with mostly mild to moderate side effects like somnolence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lemborexant, A Dual Orexin Receptor Antagonist (DORA) for the Treatment of Insomnia Disorder: Results From a Bayesian, Adaptive, Randomized, Double-Blind, Placebo-Controlled Study. Murphy, P., Moline, M., Mayleben, D., et al.[2018]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Lemborexant: First Approval. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Review of the Efficacy and Safety of Lemborexant, a Dual Receptor Orexin Antagonist (DORA), in the Treatment of Adults With Insomnia Disorder. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and safety of lemborexant in subjects previously treated with placebo for 6 months in a randomized phase 3 study. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Lack of residual morning effects of lemborexant treatment for insomnia: summary of findings across 9 clinical trials. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics and Exposure-Response Analyses for the Most Frequent Adverse Events Following Treatment With Lemborexant, an Orexin Receptor Antagonist, in Subjects With Insomnia Disorder. [2021]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and safety of lemborexant over 12 months in Asian adults with insomnia disorder. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Long-term effectiveness and safety of lemborexant in adults with insomnia disorder: results from a phase 3 randomized clinical trial. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Lemborexant, A Dual Orexin Receptor Antagonist (DORA) for the Treatment of Insomnia Disorder: Results From a Bayesian, Adaptive, Randomized, Double-Blind, Placebo-Controlled Study. [2018]