Suvorexant for Sleep Issues in Children with Autism

Overseen By Emma Baker, PhD

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Stanford University

Must not be taking: Beta-blockers, Benzodiazepines, Antiepileptics, others

Disqualifiers: Schizophrenia, Seizure disorder, Severe hepatic insufficiency, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 8 weeks

26 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing suvorexant, a sleep aid, in children and adolescents with Autism Spectrum Disorder who have sleep problems. Suvorexant helps people fall asleep and stay asleep by blocking wakefulness signals in the brain.

Will I have to stop taking my current medications?

You may need to stop taking certain medications, like beta-blockers, benzodiazepines, antiepileptic medications, melatonin, and antihistamines, as they are not allowed in the trial. If you are on Prozac, it must be stable for at least 4 weeks before joining the study.

Is Suvorexant safe for use in humans?

Suvorexant, used for treating insomnia, is generally considered safe and well-tolerated in adults, but it can cause side effects like next-morning drowsiness, muscle weakness, unusual dreams, sleepwalking, and other nighttime behaviors. It has been tested in healthy adults and elderly patients, with some concerns about safe dosing and rare adverse effects. ^{1 2 3 4 5}

How is the drug Suvorexant unique for treating sleep issues in children with autism?

Suvorexant is unique because it works by blocking orexin receptors, which are involved in wakefulness, making it different from other sleep medications that often target different pathways. This novel mechanism helps promote sleep without the same sedative effects as traditional sleep aids. ^{1 3 4 6 7}

Research Team

Antonio Hardan, MD

Principal Investigator

Stanford University

Eligibility Criteria

This trial is for children aged 13-17 with Autism Spectrum Disorder who have sleep issues, confirmed by clinical evaluation and specific tests. They must be on stable medications, willing to undergo sleep studies, and not planning any treatment changes during the study. Sexually active females must use dual contraception.

Inclusion Criteria

Willingness to provide additional saliva samples and participate in key study procedures

I am between 13 and 17 years old.

Stable medications for at least 4 weeks

Exclusion Criteria

I have tried suvorexant with no success.

History of narcolepsy

I am currently taking prescribed medications.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Suvorexant or Placebo for a 4-week period, followed by crossover to the alternate treatment for another 4 weeks

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Suvorexant

Trial Overview The trial is testing Suvorexant's effects on sleep in autistic children compared to a placebo. It's an 8-week study where participants are randomly assigned to receive either the drug or placebo first, then switch halfway without knowing which one they're taking.

Participant Groups

Group I: Suvorexant, then Placebo Experimental Treatment 2 Interventions

Participants will first receive Suvorexant for a 4-week period. A starting dose will be 5 mg at bedtime and can be increased by 5 mg only if needed and if well tolerated on a weekly basis until the maximum dose of 20 mg/day is reached. Participants will be maintained on the lowest effective dose. Participants will then receive Placebo (fake tablet) for a 4-week period. A starting dose will be 5 mg at bedtime and can be increased by 5 mg only if needed and if well tolerated on a weekly basis until the maximum dose of 20 mg/day is reached. Participants will be maintained on the lowest effective dose.

Group II: Placebo, then Suvorexant Experimental Treatment 2 Interventions

Participants will first receive Placebo (fake tablet) for a 4-week period. A starting dose will be 5 mg at bedtime and can be increased by 5 mg only if needed and if well tolerated on a weekly basis until the maximum dose of 20 mg/day is reached. Participants will be maintained on the lowest effective dose. Participants will then receive Suvorexant for a 4-week period. A starting dose will be 5 mg at bedtime and can be increased by 5 mg only if needed and if well tolerated on a weekly basis until the maximum dose of 20 mg/day is reached. Participants will be maintained on the lowest effective dose.

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?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Findings from Research

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, 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]

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]

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]

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 (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]

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]

References

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

Suvorexant for the treatment of insomnia. [2015]

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

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

3. 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]

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

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

5. 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]

6. 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]

7. 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]