Lemborexant for Insomnia in Dementia

Overseen By Shanna C Trenaman, BScPharm, PhD

Age: Any Age

Sex: Any

Trial Phase: Phase 4

Sponsor: Nova Scotia Health Authority

Must not be taking: Benzodiazepines, Sedatives

Disqualifiers: Sleep disorders contraindicating orexin antagonists

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 3

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of lemborexant, a new sleep medication, for individuals with early-onset dementia who experience sleep difficulties. Traditional sleep aids often cause issues like dizziness or dependency, posing risks for those with dementia. Lemborexant may offer a safer alternative without these side effects. The trial will compare lemborexant to a placebo over eight weeks. It is suitable for individuals diagnosed with early-onset dementia who struggle with insomnia. As a Phase 4 trial, lemborexant has already received FDA approval and demonstrated effectiveness, and this research seeks to understand its benefits for more patients.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that traditional sleeping aids may not be suitable for people with dementia, so it's possible that adjustments might be needed. Please consult with the trial team for specific guidance.

What is the safety track record for lemborexant?

Research has shown that lemborexant, a medication for insomnia, is generally well-tolerated. The FDA has approved this drug for treating insomnia in adults, indicating a good safety record for its intended use. Unlike traditional sleeping pills, lemborexant is not strongly linked to issues such as driving problems, rebound insomnia (worsening of insomnia symptoms after stopping the medication), or withdrawal symptoms.

In clinical trials, lemborexant rarely caused side effects like dizziness or drowsiness, which are common with other sleep medications. Fewer people discontinued its use due to side effects compared to other sleep aids.

While lemborexant is available on the market, studying its effects on people with early-onset dementia remains important. Overall, research suggests that lemborexant is a promising option for treating insomnia with fewer risks of side effects compared to older sleep aids. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike traditional treatments for insomnia in dementia, which often involve medications like benzodiazepines or Z-drugs, lemborexant offers a novel approach by targeting orexin receptors. Orexin is a neurotransmitter that plays a crucial role in regulating the sleep-wake cycle. By blocking orexin, lemborexant helps promote sleep without the sedative effects that can impair cognition, a significant concern for dementia patients. Researchers are excited because this mechanism could lead to better sleep quality with fewer side effects, making it a promising option for individuals who need safe, effective sleep aids.

What is the effectiveness track record for lemborexant in treating insomnia in dementia?

Research shows that lemborexant, which participants in this trial may receive, helps improve sleep quality. Compared to a placebo (a pill with no active medicine), more people reported that lemborexant improved their sleep, helped them fall asleep faster, and increased their total sleep time. Studies have found it alleviates both nighttime and daytime symptoms of insomnia and is generally well-tolerated. Importantly, lemborexant is less likely to cause issues like impaired driving or withdrawal symptoms compared to traditional sleeping pills. Its availability in Canada indicates its effectiveness in treating insomnia. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with early-onset dementia, including Alzheimer's and various other forms, who also suffer from significant insomnia. It's not suitable for those with sleep disorders that don't mix well with orexin antagonist therapy.

Inclusion Criteria

I have been diagnosed with early-onset dementia and suffer from significant insomnia.

Exclusion Criteria

I do not have sleep disorders that prevent me from taking orexin antagonist therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Participants receive study medication in an ABiBABAAB sequence over 8 weeks, alternating between placebo and lemborexant at different doses.

8 weeks

Weekly follow-up calls

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Lemborexant

Trial Overview The trial tests Lemborexant 5 MG, a new type of sleeping aid less likely to cause side effects like driving impairment or dependence seen in traditional sedatives. It aims to understand its effectiveness and tolerability in individual patients.

How Is the Trial Designed?

Group I: lemborexant Experimental Treatment 1 Intervention

The study will be an N of 1 trial over 8 weeks were treatment with lemborexant being alternated with a placebo in an "ABBABAAB" format.

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?

Nova Scotia Health Authority

Lead Sponsor

Trials

302

Recruited

95,300+

Published Research Related to This Trial

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 study of 649 patients with comorbid insomnia and psychiatric disorders, lemborexant was found to be effective, with a response rate of 64.5% and over 60% for most psychiatric conditions.

Lemborexant significantly reduced the dosage of benzodiazepines (BZs) used by patients, indicating its potential to help manage insomnia while decreasing reliance on these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and real-world efficacy of lemborexant in the treatment of comorbid insomnia. Katsuta, N., Takahashi, K., Kurosawa, Y., et al.[2023]

Lemborexant was found to be the most effective treatment for insomnia in three out of four key sleep outcomes measured objectively, including total sleep time and sleep efficiency, after four weeks of treatment, based on a systematic review of 45 studies.

The safety profile of lemborexant was similar to other insomnia treatments, with no significant differences in serious adverse events or withdrawals due to adverse events, indicating it is a safe option for treating insomnia, including in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy of lemborexant and other insomnia treatments: a network meta-analysis. McElroy, H., O'Leary, B., Adena, M., et al.[2023]

In a study of 14 cancer patients with delirium, lemborexant was effective in improving insomnia for 78.6% of participants, suggesting it can be a beneficial treatment option for sleep disturbances in this population.

Lemborexant showed a 70% efficacy rate specifically for patients experiencing hyperactive delirium, potentially allowing for lower doses of antipsychotic medications and reducing the risk of side effects like extrapyramidal symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot Study of Lemborexant for Insomnia in Cancer Patients with Delirium. Terada, T., Hirayama, T., Sadahiro, R., et al.[2022]

Suvorexant and lemborexant are effective treatments for chronic insomnia, showing significant improvements in various efficacy measures compared to placebo in a systematic review of eight randomized controlled trials.

While both medications have a generally safe profile, they are associated with some side effects like somnolence and abnormal dreams, but serious adverse events such as hallucinations and suicidal behavior did not differ significantly from placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual orexin receptor antagonists for treatment of insomnia: A systematic review and meta-analysis on randomized, double-blind, placebo-controlled trials of suvorexant and lemborexant. Khazaie, H., Sadeghi, M., Khazaie, S., et al.[2023]

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]

In a study involving 3237 participants, lemborexant (10 mg) demonstrated the most significant improvements in sleep onset, total sleep time, and wake after sleep onset compared to placebo, indicating its strong efficacy in treating insomnia.

Both lemborexant and suvorexant were associated with increased somnolence compared to placebo, highlighting a potential safety concern, particularly with lemborexant at the higher dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lemborexant vs suvorexant for insomnia: A systematic review and network meta-analysis. Kishi, T., Nomura, I., Matsuda, 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33336219/

Results From a Phase 2 Randomized Clinical Trial Conclusions: This study provides preliminary evidence of the potential utility of lemborexant as a treatment to address both nighttime and daytime symptoms in ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06093126

Lemborexant for Insomnia in a Patient With Dementia: An ... Hypothesis The investigators hypothesize that lemborexant will be effective and safe in the treatment of insomnia in adults living with both early-onset ...

3. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/abs/10.1002/alz.039039

Long‐term safety and efficacy of lemborexant in subjects with ... LEM improved circadian variables, helped consolidate nighttime sleep, and was well tolerated, over 1 month.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38748321/

Efficacy of Lemborexant in Adults ≥ 65 Years of Age with ... Compared with placebo, more subjects reported that LEM (both doses) positively impacted ability to sleep, time to fall asleep, and TST through ...

5. media-us.eisai.com media-us.eisai.com/2020-08-28-Eisai-Presents-New-Analyses-from-Phase-3-Studies-of-DAYVIGO-TM-lemborexant-CIV-for-the-Treatment-of-Insomnia-in-Adult-Patients-at-Virtual-SLEEP-2020

Eisai Presents New Analyses from Phase 3 Studies of ... An open-label pilot study evaluating the ability of patients with insomnia disorder to directly transition from zolpidem to DAYVIGO.

6. eisai.com eisai.com/news/2019/news201993.html

U.S. FDA APPROVES EISAI'S DAYVIGO™ ... DAYVIGO was approved for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance in adults.

7. sciencedirect.com sciencedirect.com/science/article/pii/S1041610225003606

Adjunctive lemborexant for managing nighttime agitation ... We present a case series of four elderly patients with AD who experienced substantial improvement in nighttime behaviors and sleep disturbances ...