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

Trial Summary

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 data supports the effectiveness of the drug lemborexant for treating insomnia in dementia?

Lemborexant has been shown to help people with insomnia fall asleep faster and stay asleep longer compared to a placebo, as seen in studies with adults. It works by blocking certain brain signals that keep you awake, and it has been approved for treating insomnia in adults in the USA and Japan. ^{1 2 3 4 5}

Is lemborexant safe for humans?

Lemborexant has been studied for treating insomnia and has a safety profile similar to other insomnia treatments, with no significant differences in serious side effects or withdrawal due to side effects. ^{1 6 7 8 9}

How is the drug lemborexant unique for treating insomnia in dementia?

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 promote wakefulness. This mechanism is different from other sleep medications that often target different pathways, such as those involving GABA (a calming neurotransmitter). ^{1 2 4 6 7}

What is the purpose of this trial?

Insomnia is a highly common, chronic disorder that is distressful for the patient but also for caregivers and can give rise to a heavy burden on the healthcare team. Sleeping aids like benzodiazepines and other sedatives (e.g., zolpidem, zopiclone) have been widely used to help treat insomnia. However, sleeping aids are also known to cause adverse drug reactions such as drowsiness and dizziness, that increases the risk of falls, driving impairment, visual impairment, cognitive impairment, and upon discontinuation may cause paradoxical rebound insomnia, delirium, and nightmares all of which exacerbate the initial insomnia. All of the negative aspects of sleeping aid use are exaggerated for older, frail adults. Some patients experience an early (young-age) onset dementia with a substantial component of insomnia. Due to the many risks associated with traditional sleeping aids they are often inappropriate in adults living with cognitive impairment and/or frailty. Lemborexant comes from a new class of medications for insomnia. Lemborexant is a dual orexin receptor antagonist that blocks the binding of wake-promoting neuropeptides orexin A and orexin B to their receptors orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R), which is thought to suppress wake drive. Unlike other traditional sleeping aids, lemborexant has not shown to be significantly associated with driving impairment, rebound insomnia, or dependence/withdrawal symptoms. Also, in clinical trials it only rarely causes the types of adverse events associated with benzodiazepines and other traditional sedatives and is less often associated with discontinuations due to adverse events. While lemborexant is available on the Canadian market it is unclear how this medication will be tolerated by patients living with an early onset dementia. Understanding the effectiveness and tolerability of lemborexant will be helpful in an N of 1 trial to understand the details of effect and effectiveness in individual patients.

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

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]

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]

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 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]

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]

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]

References

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

Lemborexant: First Approval. [2021]

2. 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]

3. Switzerland 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. [2023]

4. 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]

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

Lemborexant vs suvorexant for insomnia: A systematic review and network meta-analysis. [2021]

6. 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]

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

Safety and real-world efficacy of lemborexant in the treatment of comorbid insomnia. [2023]

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

Comparative efficacy of lemborexant and other insomnia treatments: a network meta-analysis. [2023]

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

Pilot Study of Lemborexant for Insomnia in Cancer Patients with Delirium. [2022]