Suvorexant for Insomnia

Overseen By Sarah Marrison, MD PhD

Age: 18+

Sex: Female

Trial Phase: Phase 4

Sponsor: Medical University of South Carolina

Must be taking: Estrogen modulators, Aromatase inhibitors

Must not be taking: Steroids, CYP3A inhibitors, Opioids

Disqualifiers: Severe depression, Anxiety, Sleep apnea, 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: 3

Duration: 4 weeks

44 Participants Needed

Trial Summary

What is the purpose of this trial?

Investigators propose a double-blind, placebo-controlled trial evaluating the use of the use of Suvorexant in breast cancer survivors on selective estrogen receptor modulators or aromatase inhibitors with sleep disturbance to assess the impact on insomnia symptoms and quality of life. Breast cancer survivors have an increased risk of insomnia for which Suvorexant has the has the potential ability to impact to improve sleep related outcomes and cancer survivorship outcomes. Breast cancer survivors with sleep disturbance based on an Insomnia Severity Index Score (ISI) \>15 will be randomized to either Suvorexant or placebo, with both arms receiving education on sleep hygiene.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using steroids, certain strong medications that affect liver enzymes, or other insomnia treatments.

What data supports the effectiveness of the drug Suvorexant for treating insomnia?

Research shows that Suvorexant is effective for treating insomnia, helping people fall asleep and stay asleep better over a period of 3 months. It works by blocking orexin receptors, which are involved in wakefulness, thus promoting sleep. ^{1 2 3 4 5}

Is Suvorexant safe for treating insomnia?

Suvorexant is generally considered safe for treating insomnia, but it can cause next-morning sleepiness, muscle weakness, unusual dreams, sleepwalking, and other nighttime behaviors. The FDA approved doses are 5, 10, 15, and 20 mg, with safety concerns at higher doses. It is also important to note that it may interact with other medications, but significant drug interactions are not expected at clinical doses. ^{2 3 6 7 8}

How is the drug Suvorexant different from other insomnia treatments?

Suvorexant is unique because it works by blocking orexin receptors, which are involved in wakefulness, helping to improve both sleep onset and maintenance without reducing REM sleep, unlike some other sleep aids. ^{2 3 5 9 10}

Research Team

Sarah Marrison, MD PhD

Principal Investigator

Medical University of South Carolina

Eligibility Criteria

This trial is for adult postmenopausal women who survived breast cancer, are currently on certain hormone therapies, and suffer from insomnia. They should be less than 5 years from diagnosis and finished with main cancer treatments for at least 6 weeks.

Inclusion Criteria

I am currently taking medication for hormone therapy.

I was diagnosed with my condition less than 5 years ago.

It has been over 6 weeks since I finished my main breast cancer treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Suvorexant or placebo for insomnia treatment, with a dose increase after 7 days

4 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Suvorexant

Trial Overview The study tests if Suvorexant tablets can help improve sleep in breast cancer survivors with insomnia compared to a placebo (a pill without active medication). Participants will also receive tips on good sleep habits.

Participant Groups

Group I: Suvorexant with information on sleep hygiene Experimental Treatment 1 Intervention

Participants randomized to this arm will receive 10 mg of suvorexant daily with a dose increase to 20 mg after day 7. Medication will be administered as an oral medication. Total duration of 28 days.

Group II: Placebo with information on sleep hygiene Placebo Group 1 Intervention

Participants randomized to this arm will receive 10 mg of suvorexant daily with a dose increase to 20 mg after day 7. Medication will be administered as an oral medication. Total duration of 28 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?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

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

Suvorexant, an orexin receptor antagonist, was generally well tolerated in a Phase 1 trial with 40 healthy men over 14 days, supporting its safety for use in treating insomnia.

The trial showed that higher doses (40 mg and above) resulted in 100% of subjects reporting adverse events, with common side effects including somnolence, fatigue, and headache, indicating a dose-dependent increase in side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, and Pharmacokinetics of Suvorexant: A Randomized Rising-Dose Trial in Healthy Men. Yee, KL., McCrea, J., Panebianco, D., et al.[2019]

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, is primarily metabolized in the body with 90% of its radioactivity recovered after administration, indicating effective absorption and elimination.

The drug mainly inhibits CYP3A4 and CYP2C19 enzymes but is unlikely to cause significant drug interactions at clinical doses due to low plasma concentrations, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro and in vivo characterisation of the metabolism and disposition of suvorexant in humans. Cui, D., Cabalu, T., Yee, KL., et al.[2017]

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, 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, 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, a new medication for insomnia, is generally considered safe and well tolerated in most patients.

However, there is a rare but significant adverse effect associated with suvorexant in patients with Parkinson's disease, highlighting the need for careful monitoring in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suvorexant-Induced Dream Enactment Behavior in Parkinson Disease: A Case Report. Tabata, H., Kuriyama, A., Yamao, F., 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]

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

Safety, Tolerability, and Pharmacokinetics of Suvorexant: A Randomized Rising-Dose Trial in Healthy Men. [2019]

2. 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]

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

In vitro and in vivo characterisation of the metabolism and disposition of suvorexant in humans. [2017]

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

Suvorexant: first global approval. [2021]

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. England pubmed.ncbi.nlm.nih.gov

Suvorexant for the treatment of insomnia. [2015]

7. 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]

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

Suvorexant-Induced Dream Enactment Behavior in Parkinson Disease: A Case Report. [2018]

9. 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]

10. 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]