Suvorexant for Sleep Disturbance

Recruiting at 1 trial location

Overseen By Oriana Lujan, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Columbia University

Must not be taking: CYP3 inhibitors, inducers

Disqualifiers: Cardiac surgeries, Dementia, OSA, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1-5 days

92 Participants Needed

Trial Summary

What is the purpose of this trial?

The study is a parallel group, double blind, randomized trial. Subjects will be recruited from individuals undergoing elective surgery for orthopedic, abdominal, urologic, gynecologic or spine reasons. Out of 92 subjects, one experimental group of 46 subjects will receive 20 mg Suvorexant beginning the first in-hospital night ("day 0") and continuing for their hospital stay. If the dose is not well tolerated (e.g., daytime sleepiness), then the dose may be decreased to 10 mg of Suvorexant. For blinding purposes each arm will receive two tablets (two 10 mg tablets or one 10 mg tablet and a placebo). The other control group of 46 subjects will receive placebo (two tablets) and treatment as usual.

Will I have to stop taking my current medications?

The trial requires that you do not take certain medications that affect liver enzymes, like some antibiotics, antifungals, and herbal supplements. If you're on these, you might need to stop them to participate.

What data supports the effectiveness of the drug Suvorexant for sleep disturbance?

Suvorexant, also known as Belsomra, is approved by the FDA for treating insomnia in adults, helping with both falling asleep and staying asleep. It works by blocking orexin receptors, which are involved in wakefulness, and has been shown to improve sleep quality in various studies. ^{1 2 3 4 5}

How does the drug Suvorexant differ from other treatments for sleep disturbance?

Suvorexant is unique because it works by blocking orexin receptors, which are involved in wakefulness, helping to promote sleep. This is different from other sleep medications that often work by enhancing the effects of a neurotransmitter called GABA, which calms brain activity. ^{1 2 4 5 6}

Research Team

Paul S. Garcia, MD PhD

Principal Investigator

Columbia University

Eligibility Criteria

This trial is for people aged 50-90 who are having elective surgeries like hip replacement or hernia repair and have had trouble sleeping at least three times a week over the last three months. It's not for those with severe sleep apnea, chronic pain, certain heart surgeries, mental health issues, dementia, or taking drugs that affect Suvorexant.

Inclusion Criteria

I am between 50 and 90 years old.

I am scheduled for surgery (like hip replacement or hernia repair) with a hospital stay of at least 24 hours.

I have had trouble falling asleep or staying asleep at least 3 nights a week for the last 3 months.

Exclusion Criteria

This study does not include children, pregnant women, or patients who do not speak English.

I am not taking any medications that strongly affect liver enzymes.

I take opioid medication for ongoing pain.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 20 mg Suvorexant or placebo starting the first in-hospital night and continuing for their hospital stay, with a maximum of 5 days

1-5 days

Daily in-hospital administration

Follow-up

Participants are monitored for sleep quality and cognitive performance using EEG and self-report scales

Up to 5 days post-surgery

Treatment Details

Interventions

• Placebo
• Suvorexant

Trial Overview The study tests if Suvorexant helps with sleep problems after surgery compared to a placebo. Participants will be randomly assigned to either get Suvorexant (20 mg reducing to 10 mg if needed) or placebo pills during their hospital stay.

Participant Groups

Group I: Suvorexant administration Experimental Treatment 1 Intervention

Subjects will receive 20 mg Suvorexant beginning the first in-hospital night ("day 0") and continuing for their hospital stay. If the dose is not well tolerated (e.g., daytime sleepiness), then the dose may be decreased to 10 mg of Suvorexant. For blinding purposes, each arm will receive two tablets (two 10 mg tablets or one 10 mg tablet and a placebo). Suvorexant will be administered beginning on the night after surgery and through the hospitalization period (it is estimated that stays will be 1-3 days; subjects will be followed for a maximum of 5 days).

Group II: Placebo administration Placebo Group 1 Intervention

Subjects will receive a placebo (two tablets) and treatment as usual. The placebo will be administered beginning on the night after surgery and through the hospitalization period (it is estimated that stays will be 1-3 days; subjects will be followed for a maximum of 5 days).

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

Approved in United States as Belsomra for:

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

Approved in Japan as Belsomra for:

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

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

This trial will assess the efficacy of suvorexant, an FDA-approved sleep aid, in reducing nighttime wakefulness and delirium in 120 older cardiac surgery patients in the ICU.

The study aims to determine if suvorexant can improve sleep quality and reduce the incidence of postoperative delirium, which is important for recovery in this vulnerable population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study protocol for a randomised controlled trial evaluating the effects of the orexin receptor antagonist suvorexant on sleep architecture and delirium in the intensive care unit. Azimaraghi, O., Hammer, M., Santer, P., et al.[2021]

Suvorexant (Belsomra®) is a new sleep medication that works by blocking orexin neurons, leading to a rapid onset of sleep, and is effective at a prescribed dose of 10 mg before bedtime.

A highly sensitive urine assay was developed to accurately identify and quantify suvorexant, demonstrating excellent precision and stability, which is crucial for monitoring its use due to potential misuse and interactions with other sedatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of Suvorexant in Urine Using Liquid Chromatography-Quadrupole/Time-of-Flight Mass Spectrometry (LC-Q/TOF-MS). Sullinger, S., Bryand, K., Kerrigan, S.[2017]

Suvorexant, an orexin receptor antagonist, was found to be generally safe and well tolerated over a 1-year treatment period for patients with primary insomnia, with a notable incidence of somnolence as a common side effect.

In the first month of treatment, suvorexant significantly improved subjective total sleep time by an average of 38.7 minutes and reduced time to sleep onset by 18.0 minutes compared to placebo, indicating its efficacy in enhancing sleep quality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of suvorexant during 1-year treatment of insomnia with subsequent abrupt treatment discontinuation: a phase 3 randomised, double-blind, placebo-controlled trial. Michelson, D., Snyder, E., Paradis, E., et al.[2022]

Suvorexant is a first-in-class medication that works by blocking orexin receptors, which are involved in regulating wakefulness, thereby promoting sleep for individuals with insomnia.

Approved in the US in August 2014, suvorexant is effective for both sleep onset and sleep maintenance insomnia, and is in the process of being registered in other countries, indicating its potential global impact on treating sleep disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suvorexant: first global approval. Yang, LP.[2021]

Suvorexant, an orexin receptor antagonist, significantly improved sleep parameters in healthy young men, with all doses (10 mg, 50 mg, and 100 mg) showing better sleep compared to placebo, particularly in reducing the time to persistent sleep and wake after sleep onset.

While suvorexant was generally well tolerated, higher doses (50 mg and 100 mg) showed some next-day residual effects, such as reduced alertness and slower reaction times, indicating a need for careful dosing in potential therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of suvorexant, an orexin receptor antagonist, on sleep parameters as measured by polysomnography in healthy men. Sun, H., Kennedy, WP., Wilbraham, D., et al.[2022]

A reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to measure suvorexant levels in human plasma, demonstrating high precision and accuracy across a wide concentration range (1-1000 ng/mL).

The method has been validated for stability and can support clinical studies for suvorexant, showing that plasma samples remain stable for up to 25 months at -20°C, which is crucial for long-term studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of suvorexant in human plasma using 96-well liquid-liquid extraction and HPLC with tandem mass spectrometric detection. Breidinger, SA., Simpson, RC., Mangin, E., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Study protocol for a randomised controlled trial evaluating the effects of the orexin receptor antagonist suvorexant on sleep architecture and delirium in the intensive care unit. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Identification of Suvorexant in Urine Using Liquid Chromatography-Quadrupole/Time-of-Flight Mass Spectrometry (LC-Q/TOF-MS). [2017]

3. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of suvorexant during 1-year treatment of insomnia with subsequent abrupt treatment discontinuation: a phase 3 randomised, double-blind, placebo-controlled trial. [2022]

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

Suvorexant: first global approval. [2021]

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

Effects of suvorexant, an orexin receptor antagonist, on sleep parameters as measured by polysomnography in healthy men. [2022]

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

Determination of suvorexant in human plasma using 96-well liquid-liquid extraction and HPLC with tandem mass spectrometric detection. [2019]