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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to compare the side effects of two sleep medications, suvorexant (Belsomra) and zolpidem (Ambien), to assess their impact on performance, particularly in military settings. Participants will help researchers understand how these sleep aids differ in their effects. The trial seeks healthy individuals who typically sleep 6-9 hours a night and do not rely on sleep aids or have sleep disorders. Participants must understand English well, as cognitive tests are part of the study. As an Early Phase 1 trial, this research focuses on understanding how these medications work in people, offering participants a chance to contribute to foundational sleep research.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both suvorexant and zolpidem are generally safe for healthy individuals. Studies have tested suvorexant for up to 14 days, and it was mostly well-tolerated, with most participants experiencing no serious side effects. In another study, combining suvorexant with another drug did not raise major safety concerns.

Zolpidem has also undergone extensive study. It is commonly used for sleep problems and is considered safe when used as directed. Research indicates that it is well-tolerated by both adults and older individuals, with most side effects being mild and manageable.

Both medications have demonstrated a good safety record in healthy people in previous studies. However, individuals should consider their own health and consult a healthcare professional before joining any trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer new ways to tackle sleep issues. Suvorexant is unique because it targets orexin receptors in the brain, which play a key role in wakefulness, making it different from most sleep aids that simply enhance sleep-inducing chemicals like GABA. Zolpidem, on the other hand, is a well-known medication that acts quickly to help with sleep onset. These treatments could provide alternative options for people who struggle with sleep, each working through distinct mechanisms to potentially improve sleep quality.

What evidence suggests that this trial's treatments could be effective for sleep induction?

In this trial, participants will receive either suvorexant, zolpidem, or a placebo. Research has shown that suvorexant effectively treats insomnia, helping people fall asleep faster and stay asleep longer compared to a placebo, with improvements observed over three months. Similarly, zolpidem has also proven effective for insomnia by reducing the time it takes to fall asleep and increasing total sleep time. Studies have found that zolpidem remains effective for up to eight months. Both treatments can improve sleep, but they may have different side effects. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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, 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, 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]

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]

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, 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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4591519/

Suvorexant in insomnia: efficacy, safety and place in therapy Similarly, suvorexant 20/15 mg was more effective than placebo in improving sleep maintenance, measured by sTST and WASO, at months 1 and 3 (p < 0.001). Changes ...

2. journals.lww.com journals.lww.com/atmr/fulltext/2024/07000/the_effectiveness_of_suvorexant_compared_to_a.46.aspx

The Effectiveness of Suvorexant Compared to a Placebo in ... Overall, the results show that suvorexant is an effective treatment for insomnia although it appears that the degree of effectiveness varies somewhat. More ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01097616

NCT01097616 | Safety and Efficacy Study of Suvorexant in ... This is a multicenter study to test the hypothesis that suvorexant (MK-4305) is superior to placebo in improving insomnia as measured by change from ...

4. jcsm.aasm.org jcsm.aasm.org/doi/10.5664/jcsm.6116

Suvorexant in Patients with Insomnia: Pooled Analyses of ... Study Impact: The results of the pooled analysis showed that suvorexant 20/15 mg improved sleep onset and maintenance over 3 months of nightly treatment and was ...

5. nature.com nature.com/articles/s41398-025-03439-8

a systematic review and network meta-analysis Therefore, any DORAs may be expected to improve overall sleep quality when administered in doses appropriate for each individual with insomnia.

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2020/204569s006lbl.pdf

Belsomra - accessdata.fda.gov In clinical pharmacology studies, healthy subjects who were administered morning doses of up to 240 mg of suvorexant showed dose-dependent increases in the ...

7. merck.com merck.com/docs/product/safety-data-sheets/hh-sds/Suvorexant%20Formulation_HH_CA_EN.pdf

SAFETY DATA SHEET Suvorexant Formulation When using do not eat, drink or smoke. Wash contaminated clothing before re-use. The effective operation of a facility should include review of engineering ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02750306

NCT02750306 | Safety and Efficacy of Suvorexant (MK- ... This study aims to examine the safety and efficacy of suvorexant (MK-4305) to improve sleep in individuals with Alzheimer's disease (AD).

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/29705869/

Safety, Tolerability, and Pharmacokinetics of Suvorexant Conclusions: Suvorexant was generally well tolerated after single and multiple dosing for 14 days. The findings support the once-nightly dosing regimen.

10. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2014/204569s000lbledt.pdf

FULL PRESCRIBING INFORMATION Reference ID: 3610408 An interaction study with a single dose of 40 mg suvorexant and paroxetine 20 mg at steady-state levels in healthy subjects did not demonstrate a clinically ...