Lemborexant for Insomnia and Depression

(MDD Trial)

Overseen By Venkat Bhat, MD, MSc

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Unity Health Toronto

Must not be taking: Sleep aids, Antidepressants

Disqualifiers: Pregnancy, Substance abuse, Bipolar, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you keep any current psychiatric medications unchanged for 4 weeks before screening and throughout the study. Additionally, you must not have taken any medications affecting sleep-wake function for at least 4 weeks before starting the study.

What data supports the effectiveness of the drug lemborexant for treating insomnia and depression?

Lemborexant has been shown to be effective in treating insomnia, as it helps people fall asleep faster and stay asleep longer without causing next-morning drowsiness. While there is no direct evidence for its use in depression, improving sleep can often help alleviate some symptoms of depression. ^{1 2 3 4 5}

How is the drug lemborexant unique for treating insomnia and depression?

Lemborexant is unique because it is a dual orexin receptor antagonist, which means it works by blocking the action of orexins (chemicals in the brain that help keep you awake), making it different from other insomnia treatments that often target different pathways. It is specifically approved for treating insomnia, and its potential use for depression is being explored, which could offer a novel approach if proven effective. ^{2 3 4 5 6}

What is the purpose of this trial?

The goal of this clinical trial is to learn if Lemborexant works to treat residual insomnia in adults with depression that is being treated. It will also learn about how practical, tolerable, and effective Lemborexant is. The main questions it aims to answer are: * Does Lemborexant help participants improve sleep and reduce insomnia symptoms? * How practical is it to use Lemborexant (how many participants join, drop out, and follow the study rules)? How do participants feel about using it (based on surveys and interviews)? Researchers will compare Lemborexant to a placebo (a look-alike substance that contains no drug) to see if Lemborexant works to treat residual insomnia in adequately treated major depressive disorder. Participants will: * Take Lemborexant or a placebo every day for 6 weeks (2 weeks at 5 mg then 4 weeks at 10 mg) * Complete clinical assessments and in-person study visits * Maintain a digital sleep diary and complete daily and weekly self-report ecological momentary assessments (EMAs) * Use a wearable device which will be used to collect and monitor physiological data

Research Team

Venkat Bhat, MD, MSc

Principal Investigator

Unity Health Toronto

Eligibility Criteria

Adults with major depressive disorder (MDD) who are currently being treated but still experience insomnia can join this trial. They must be willing to take a daily pill, maintain a sleep diary, wear a monitoring device, and attend study visits.

Inclusion Criteria

Meet specific sleep criteria at screening visits 1 and 2

Own a smartphone and have reliable internet access

Provide written informed consent

Exclusion Criteria

Previously participated in any clinical trial of lemborexant

Have known sensitivity to lemborexant or its excipients

I am not using any birth control methods approved by this study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants take Lemborexant or placebo daily for 6 weeks, with clinical assessments and in-person visits

6 weeks

Multiple in-person visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

7 weeks

Treatment Details

Interventions

• Lemborexant

Trial Overview The trial is testing Lemborexant against a placebo to see if it improves sleep in people with depression-related insomnia. Participants will start with a lower dose for 2 weeks and then increase the dose for another 4 weeks while their experiences are monitored.

Participant Groups

Group I: Lemborexant Experimental Treatment 1 Intervention

Participants will take a 5 mg pill of lemborexant daily for two weeks, followed by a dosage increase to 10 mg daily for the next four weeks (6 weeks total).

Group II: Placebo Placebo Group 1 Intervention

Participants will take a 5 mg of placebo pill daily for 2 weeks then 10 mg daily for 4 weeks (total of 6 weeks).

Who Is Running the Clinical Trial?

Unity Health Toronto

Lead Sponsor

Trials

572

Recruited

470,000+

Toronto Metropolitan University

Collaborator

Trials

95

Recruited

19,300+

University of Toronto

Collaborator

Trials

739

Recruited

1,125,000+

Centre for Addiction and Mental Health

Collaborator

Trials

388

Recruited

84,200+

Findings from Research

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]

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]

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 12-month phase 3 study involving 949 subjects with moderate to severe insomnia, lemborexant significantly reduced insomnia severity compared to placebo, with improvements maintained over time.

Lemborexant treatment resulted in higher rates of clinically meaningful responses and remissions, with 44%-57% of subjects achieving a significant reduction in insomnia severity after 1 to 6 months, compared to 30%-41% in the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of lemborexant treatment on insomnia severity: analyses from a 12-month study of adults with insomnia disorder. Roth, T., Rosenberg, R., Morin, CM., et al.[2022]

References

1. 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]

2. 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]

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

Effect of alcohol coadministration on the pharmacodynamics, pharmacokinetics, and safety of lemborexant: A randomized, placebo-controlled crossover study. [2022]

4. 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]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Impact of lemborexant treatment on insomnia severity: analyses from a 12-month study of adults with insomnia disorder. [2022]

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

Respiratory Safety of Lemborexant in Healthy Subjects: A Single-Dose, Randomized, Double-Blind, Placebo-Controlled, Crossover Study. [2021]