Sleep Medications for Healthy Volunteers

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Walter Reed Army Institute of Research (WRAIR)

Must not be taking: Sleep aids, Benzodiazepines, Amphetamines, others

Disqualifiers: Sleep disorders, Neurologic disorders, Cardiovascular disease, Psychiatric disorder, others

Compensation: Varies

Number of Visits: Unknown

Duration: 5 days

90 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary objective of this study is to evaluate two pharmacotherapeutic approaches to sleep induction, both of which have been shown to be effective hypnotics, but may have unique side effect profiles. These profiles may have markedly different impacts on performance in a military setting. In this randomized, double-blind, placebo controlled study, the side effects of these drugs will be compared - suvorexant, a dual orexin receptor antagonist and zolpidem, a non-benzodiazepine gamma-aminobutyric acid (GABA) A agonist - in healthy controls comparable in age and gender to the target military population.

Do I need to stop taking my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but it mentions that any use of prescription or over-the-counter sleep aids in the past 3 months may exclude you. It's best to discuss your current medications with the study medical investigator.

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

Suvorexant, also known as Belsomra, is approved by the FDA for treating insomnia, helping people fall asleep and stay asleep. Studies show it is effective in improving sleep onset and maintenance, although there are concerns about next-morning drowsiness and other side effects. ^{1 2 3 4 5}

Is suvorexant safe for humans?

Suvorexant, approved for treating insomnia, is generally considered safe at doses of 5-20 mg, but it may cause next-morning drowsiness, muscle weakness, unusual dreams, sleepwalking, and other nighttime behaviors. It has a low potential for abuse and is classified as a Schedule IV drug. ^{1 2 3 6 7}

How is the drug Suvorexant different from other sleep medications?

Suvorexant is unique because it works by blocking orexin receptors, which are involved in wakefulness, making it different from other sleep medications that typically target GABA receptors. This novel mechanism helps promote sleep without the same level of next-day drowsiness often associated with traditional sleep aids. ^{1 2 8 9 10}

Eligibility Criteria

Healthy English-speaking adults aged 18-39 can join this trial. Women must use birth control if sexually active. Excluded are those with irregular sleep schedules, depression, kidney/liver disease, heavy alcohol/drug use, certain medical conditions or extreme morning/evening preferences.

Inclusion Criteria

I am using birth control.

Volunteers must have learned English as their first language

I am a healthy adult between 18 and 39 years old and not pregnant or breastfeeding.

Exclusion Criteria

Inability to read and sign consent

Incarceration during Phase 1

I have liver disease or significant liver problems.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either Suvorexant, Zolpidem, or placebo to evaluate their effects on sleep induction and side effect profiles

5 days

Daily visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

Treatment Details

Interventions

• Placebos
• Suvorexant
• Zolpidem

Trial Overview The study tests Suvorexant (10 mg) and Zolpidem against a placebo to see which is better for sleep induction without affecting performance. It's randomized and double-blind, meaning participants and researchers don't know who gets which treatment.

Participant Groups

Group I: Zolpidem Arm Active Control 2 Interventions

5 mg of Zolpidem

Group II: Suvorexant Arm Active Control 2 Interventions

10 mg of Suvorexant

Group III: Placebo Placebo Group 1 Intervention

10mg of Avicel

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?

Walter Reed Army Institute of Research (WRAIR)

Lead Sponsor

Trials

111

Recruited

108,000+

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, the first orexin receptor antagonist approved by the FDA for treating insomnia, has been shown to effectively induce and maintain sleep in adult and elderly patients over treatment periods of up to 12 months.

While the FDA approved doses of 5, 10, 15, and 20 mg due to concerns about safety and next-morning effects like somnolence and unusual behaviors, suvorexant represents a novel approach to insomnia treatment, potentially leading to new therapies targeting orexin receptors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suvorexant for the treatment of insomnia. Jacobson, LH., Callander, GE., Hoyer, D.[2015]

Suvorexant is the first orexin receptor antagonist approved for treating insomnia, showing significant efficacy in reducing sleep latency and improving sleep maintenance in both non-elderly and elderly patients, based on two Phase 3 clinical trials with a total duration of 3 months.

The most common side effect was somnolence, with a number needed to harm (NNH) of 13 for higher doses, indicating that while suvorexant is effective, it does carry some risk of next-day sedation, leading to a recommended dose range of 10-20 mg.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suvorexant for insomnia: a systematic review of the efficacy and safety profile for this newly approved hypnotic - what is the number needed to treat, number needed to harm and likelihood to be helped or harmed? Citrome, L.[2018]

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, a dual orexin receptor antagonist approved for insomnia, showed low potential for abuse in nonclinical studies, including tests for physical dependence and reinforcing efficacy in animal models.

The absence of significant withdrawal symptoms and lack of behavioral reinforcement in studies suggest that suvorexant is unlikely to be abused in humans, leading to its classification as a Schedule IV controlled substance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical assessment of the abuse potential of the orexin receptor antagonist, suvorexant. Born, S., Gauvin, DV., Mukherjee, S., et al.[2018]

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 (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, a dual orexin receptor antagonist used for treating insomnia, promotes sleep by blocking orexin receptors, and has been available since 2014 in the USA and Japan.

This report presents the first quantitation of suvorexant in postmortem specimens from three autopsy cases, indicating its potential relevance in forensic toxicology as its use may increase.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tissue Distribution of Suvorexant in Three Forensic Autopsy Cases. Waters, B., Hara, K., Ikematsu, N., et al.[2018]

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]

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

Suvorexant for the treatment of insomnia. [2015]

3. India pubmed.ncbi.nlm.nih.gov

Suvorexant for insomnia: a systematic review of the efficacy and safety profile for this newly approved hypnotic - what is the number needed to treat, number needed to harm and likelihood to be helped or harmed? [2018]

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

Efficacy of eight months of nightly zolpidem: a prospective placebo-controlled study. [2023]

5. 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]

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

Preclinical assessment of the abuse potential of the orexin receptor antagonist, suvorexant. [2018]

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

Suvorexant: first global approval. [2021]

8. 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]

9. England pubmed.ncbi.nlm.nih.gov

Tissue Distribution of Suvorexant in Three Forensic Autopsy Cases. [2018]

10. 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]