Suvorexant for Opioid Use Disorder

Recruiting in Palo Alto (17 mi)

Overseen by Justin Strickland, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: Johns Hopkins University

Disqualifiers: Pregnant, Breastfeeding, Seeking opioid treatment, others

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This research is being done to evaluate whether suvorexant may reduce the use of, subjective liking, and demand for various drugs.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team to understand how your medications might interact with the trial.

What data supports the effectiveness of the drug Suvorexant for treating opioid use disorder?

Research suggests that Suvorexant, originally used for insomnia, may help reduce drug-seeking behavior and improve sleep in people with opioid use disorder, especially during withdrawal. ^{1 2 3 4 5}

Is suvorexant safe for humans?

Suvorexant, also known as Belsomra, has been studied for its safety in humans primarily for treating insomnia. It is generally considered safe at doses of 5-20 mg, though higher doses may cause next-morning drowsiness, unusual dreams, and other nighttime behaviors. Studies suggest it has low potential for abuse and does not significantly interact with other drugs at clinical doses. ^{1 3 4 6 7}

How is the drug Suvorexant unique in treating opioid use disorder?

Suvorexant is unique because it is a dual orexin receptor antagonist originally approved for insomnia, and it works by blocking orexin receptors involved in arousal and drug-seeking behavior, which may help reduce opioid cravings and prevent relapse. ^{1 2 3 5 6}

Research Team

Justin Strickland, PhD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for adults aged 18-65 with moderate to severe Opioid Use Disorder, as defined by the DSM-5. Participants must have a history of substance use (details blinded), be in good health overall, and pass medical screenings including urine and blood tests. Those seeking opioid treatment, pregnant or breastfeeding individuals, or those with significant mental/physical disorders that could affect participation are excluded.

Inclusion Criteria

Meets Diagnostic and Statistical Manual-5 criteria for Opioid Use Disorder (OUD) (moderate or severe)

I am between 18 and 65 years old.

Lifetime substance use history criterion [blinded]

Exclusion Criteria

Pregnant or breast feeding

Seeking opioid use treatment

Significant mental health or physical disorder that is expected to interfere with study participation as assessed by the study physicians or medical staff

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 visit

Inpatient Stay

Participants undergo a 14 to 16 day inpatient stay where they are stabilized on hydromorphone and randomly assigned to receive either suvorexant or placebo. They complete 5 experimental sessions with blinded study medications.

2 weeks

Daily monitoring and experimental sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Treatment Details

Interventions

• Suvorexant (Other)

Trial Overview The study aims to see if suvorexant (20mg/day) can reduce usage, enjoyment, and craving for opioids compared to other undisclosed drugs (Drug A-D) and a placebo. The effectiveness of suvorexant against these blinded drugs will help understand its potential as a treatment option.

Participant Groups

Group I: Suvorexant (20mg/day) Experimental Treatment 5 Interventions

Double blind administration of suvorexant once per day during residential stay until discharge

Group II: Placebo Placebo Group 5 Interventions

Double blind administration of placebo once per day during residential stay until discharge

Suvorexant is already approved in Japan for the following indications:

Approved in Japan as Belsomra for:

• Insomnia characterized by difficulties with sleep onset and/or sleep maintenance

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Theodore DeWeese

Johns Hopkins University

Chief Executive Officer since 2023

MD from an unspecified institution

Allen Kachalia

Johns Hopkins University

Chief Medical Officer since 2023

MD from an unspecified institution

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Dr. Nora Volkow

National Institute on Drug Abuse (NIDA)

Chief Executive Officer since 2003

MD from National Autonomous University of Mexico

Dr. Nora Volkow

National Institute on Drug Abuse (NIDA)

Chief Medical Officer since 2003

MD from National Autonomous University of Mexico

Findings from Research

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, 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]

In a study involving 38 participants with opioid use disorder, the dual-orexin receptor antagonist suvorexant improved total sleep time during a buprenorphine/naloxone taper, suggesting it may help with sleep disturbances associated with opioid withdrawal.

Participants receiving suvorexant showed decreased opioid withdrawal symptoms during the post-taper period, indicating its potential efficacy in managing withdrawal effects without increasing the risk of abuse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suvorexant ameliorated sleep disturbance, opioid withdrawal, and craving during a buprenorphine taper. Huhn, AS., Finan, PH., Gamaldo, CE., 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 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, 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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

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

2. Switzerland pubmed.ncbi.nlm.nih.gov

Suvorexant, an FDA-approved dual orexin receptor antagonist, reduces oxycodone self-administration and conditioned reinstatement in male and female rats. [2023]

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

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

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

Suvorexant ameliorated sleep disturbance, opioid withdrawal, and craving during a buprenorphine taper. [2022]

5. 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]

6. England pubmed.ncbi.nlm.nih.gov

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

7. England pubmed.ncbi.nlm.nih.gov

Suvorexant for the treatment of insomnia. [2015]