Suvorexant for Sleep Disturbance

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Paul S. Garcia, MD PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: Columbia University

Must not be taking: CYP3 inhibitors, inducers

Disqualifiers: Cardiac surgeries, Dementia, OSA, others

Prior Safety Data

Approved in 3 Jurisdictions

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.

Trial 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 (Behavioural Intervention)
• Suvorexant (Orexin Receptor Antagonist)

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, Australia, 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 Australia 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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

NewYork-Presbyterian Allen Hospital/CUMC Milstein Hospital Building New York, NY

Columbia University Irving Medical Center/NewYork-Presbyterian Milstein Hospital/New York State Psychiatric Institute New York, NY

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1529

Patients Recruited

2,832,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4096

Patients Recruited

5,232,000+

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] Insomnia frequently occurs in patients admitted to an intensive care unit (ICU). Sleep-promoting agents may reduce rapid eye movement sleep and have deliriogenic effects. Suvorexant (Belsomra) is an orexin receptor antagonist with Food and Drug Administration (FDA) approval for the treatment of adult insomnia, which improves sleep onset and maintenance as well as subjective measures of quality of sleep. This trial will evaluate the efficacy of postoperative oral suvorexant treatment on night-time wakefulness after persistent sleep onset as well as the incidence and duration of delirium among adult cardiac surgical patients.

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] Suvorexant (Belsomra®) is a new hypnotic drug with a novel mechanism of action. In prescribed doses of 10 mg before bedtime, the drug produces rapid onset of sleep by inhibiting the orexin neurons of the arousal system, promoting decreased wakefulness. Suvorexant is a potent and highly selective dual orexin receptor antagonist. Sedative hypnotics are of forensic importance due to their widespread use, potential for additive effects with other central nervous system depressants, impairing effects and potential for misuse. In this report we describe a highly sensitive assay for the identification and quantification of suvorexant in urine. Suvorexant was isolated using liquid/liquid extraction (LLE) and identified using liquid chromatography-quadrupole/time-of-flight mass spectrometry. Suvorexant was quantified using a quadratic calibration model between 5 and 250 ng/mL (R2 = 1.000, n = 6). Processed sample stability was demonstrated for up to 24 h. The limit of detection was 0.5 ng/mL and the limit of quantification (LOQ) was 5 ng/mL. The accuracy, bias and precision of the assay at the LOQ were 99% (81-117%), -1% and 12% (n = 18). Intraassay (n = 5) and interassay (n = 15) precision (% CV) at 10, 50 and 200 ng/mL were ≤8%, and bias ranged from -2% to 4% (98-104% accuracy). No qualitative interferences were detected from matrix, internal standard or 50 common drugs. Matrix effects evaluated at low and high concentrations were -16% and -9%, respectively, and produced CVs of 11% and 5% (n = 20). Suvorexant is a new drug of forensic importance. In this report we describe how a simple acidic/neutral LLE can be used to isolate this lipophilic drug with high recoveries and sound analytical performance.

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] Suvorexant (MK-4305) is an orexin receptor antagonist shown to be efficacious for insomnia over 3 months. We aimed to assess its clinical profile during and after 1 year of treatment.

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

Suvorexant: first global approval. [2021] Suvorexant (Belsomra(®)), a first-in-class, orally active dual orexin-1 receptor and orexin-2 receptor antagonist, has been developed by Merck for the treatment of insomnia. Variations in the levels of the neuropeptides orexin A and orexin B have been linked to circadian rhythms and wakefulness. Orexin-producing neurons in the lateral hypothalamus regulate wakefulness by signalling through orexin receptors. Blockade of orexin receptors is known to promote sleep. Suvorexant was approved in the US in August 2014 for the treatment of adults with sleep onset and/or sleep maintenance insomnia. The drug is also preregistration in Japan, with approval submissions planned for other countries worldwide for this indication. This article summarizes the milestones in the development of suvorexant leading to this first approval for insomnia.

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] Suvorexant (MK-4305) is an orexin receptor antagonist being developed for the treatment of insomnia. This report describes the effects of nighttime administration of suvorexant on polysomnography (PSG) sleep parameters in healthy young men.

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] A method, using liquid chromatography with tandem mass spectrometric detection (LC-MS/MS), was developed for the determination of suvorexant (MK-4305, Belsomra(®)), a selective dual orexin receptor antagonist for the treatment insomnia, in human plasma over the concentration range of 1-1000ng/mL. Stable isotope labeled (13)C(2)H3-suvorexant was used as an internal standard. The sample preparation procedure utilized liquid-liquid extraction, in the 96-well format, of a 100μL plasma sample with methyl t-butyl ether. The compounds were chromatographed under isocratic conditions on a Waters dC18 (50×2.1mm, 3μm) column with a mobile phase consisting of 30/70 (v/v %) 10mM ammonium formate, pH3/acetonitrile at a flow rate of 0.3mL/min. Multiple reaction monitoring of the precursor-to-product ion pairs for suvorexant (m/z 451→186) and (13)C(2)H3-suvorexant (m/z 455→190) on an Applied Biosystems API 4000 tandem mass spectrometer was used for quantitation. Intraday assay precision, assessed in six different lots of control plasma, was within 10% CV at all concentrations, while assay accuracy ranged from 95.6 to 105.0% of nominal. Quality control (QC) samples in plasma were stored at -20°C. Initial within day analysis of QCs after one freeze-thaw cycle showed accuracy within 9.5% of nominal with precision (CV) of 6.7% or less. The plasma QC samples were demonstrated to be stable for up to 25 months at -20°C. The method described has been used to support clinical studies during Phase I through III of clinical development.