Suvorexant for Insomnia

(SUV Trial)

Recruiting at 1 trial location

Overseen By Lara Ray, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Pharmacotherapies for Alcohol and Substance Use Disorders Alliance

Must not be taking: CYP3A modulators

Disqualifiers: Substance use disorder, Schizophrenia, Bipolar, 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: 2 weeks

76 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This study is to determine if suvorexant (SUV) will reduce insomnia in 76 men and women veteran and non-veterans between the ages 21-65 with posttraumatic stress disorder (PTSD) symptoms and alcohol use disorder (AUD). All participants will have a 7-day placebo run-in period, followed by a random assignment to receive placebo or suvorexant for an additonal 14 days. Post-randomization, participants will attempt to stop drinking for two weeks and will complete daily virtual diaries and study outcome assessments via in-person clinic visits on days 7 and 14.

Will I have to stop taking my current medications?

The trial requires participants to stop taking all other sleep medications starting 7 days before the study begins. Additionally, if you are on a prescription medication that conflicts with suvorexant, you may need to stop taking it.

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 of 5-20 mg, and it is important to follow these guidelines to minimize risks. Rare side effects have been reported, such as dream enactment in Parkinson's patients. ^{1 2 3 4 5}

How is the drug Suvorexant unique for treating insomnia?

Suvorexant is unique because it works by blocking orexin receptors, which are involved in wakefulness, helping to improve both sleep onset and maintenance without significantly altering sleep architecture. This mechanism is different from other insomnia treatments that often target GABA receptors or melatonin pathways. ^{3 4 6 7 8}

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

Suvorexant has been shown to be effective for treating insomnia by helping people fall asleep and stay asleep, as demonstrated in a study where it was effective over a 3-month period. It is approved by the FDA for this use, indicating its effectiveness in improving sleep onset and maintenance. ^{3 4 8 9 10}

Who Is on the Research Team?

Lara Ray, PhD

Principal Investigator

University of California, Los Angeles

Scott Lane, PhD

Principal Investigator

The University of Texas Health Science Center, Houston

Are You a Good Fit for This Trial?

This trial is for men and women aged 21-65, both veterans and non-veterans, who are experiencing symptoms of PTSD along with alcohol use disorder. Participants should be willing to attempt stopping drinking for two weeks and complete daily virtual diaries as well as in-person clinic visits.

Inclusion Criteria

Must have an ISI score equal to or > 7

Intrinsic motivation to reduce or quit drinking and to receive PTSD treatment

Agree to abstain from all other sleep medications

Exclusion Criteria

Current DSM-5 diagnosis of substance use disorder for substances other than alcohol, nicotine, or marijuana

Lifetime DSM-5 diagnosis of schizophrenia, bipolar disorder, or psychotic disorder

Positive urine test for recreational drugs other than marijuana at screening

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Placebo Run-in

Participants undergo a 7-day placebo run-in period before randomization

1 week

1 visit (in-person)

Treatment

Participants are randomly assigned to receive either suvorexant or placebo for 14 days, with daily virtual diaries and in-person visits on days 7 and 14

2 weeks

2 visits (in-person), daily virtual diaries

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Suvorexant

Trial Overview The study tests if suvorexant (SUV) can help reduce insomnia in participants with PTSD and AUD. After a week on placebo, they're randomly chosen to either continue with the placebo or switch to suvorexant for another two weeks while trying to abstain from alcohol.

How Is the Trial Designed?

Group I: 10mg and 20mg Suvorexant (SUV) Active Control 1 Intervention

Participants will be randomly assigned to receive SUV (10mg (Days 0-6) and 20mg (Days 7-13)).

Group II: Placebo Placebo Group 1 Intervention

Participants will be randomly assigned to receive matched placebo (Days 0-13).

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?

Pharmacotherapies for Alcohol and Substance Use Disorders Alliance

Lead Sponsor

Trials

9

Recruited

350+

University of California, Los Angeles

Collaborator

Trials

1,594

Recruited

10,430,000+

The University of Texas Health Science Center, Houston

Collaborator

Trials

974

Recruited

361,000+

Published Research Related to This Trial

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, 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, 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]

Citations

1. 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]

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

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

3. 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]

4. England pubmed.ncbi.nlm.nih.gov

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

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

Suvorexant: first global approval. [2021]

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]