Suvorexant for Opioid Use Disorder

Overseen By Kelly E Dunn, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Johns Hopkins University

Must be taking: Buprenorphine/naloxone

Must not be taking: Benzodiazepines, Suvorexant

Disqualifiers: Pregnancy, Alcohol use disorder, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

120 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a 4-week, randomized-controlled trial of suvorexant vs placebo in persons with opioid use disorder who have recent fentanyl exposure. Participants will first undergo a 5-day residential phase wherein participants are stabilized on sublingual buprenorphine/naloxone, followed by a 3-week outpatient phase wherein participants are maintained on sublingual buprenorphine/naloxone and transitioned to extended-release buprenorphine).

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 currently using benzodiazepines or medications for insomnia. You will be stabilized on buprenorphine/naloxone during the trial.

Is suvorexant safe for humans?

Suvorexant, also known as Belsomra, has been studied for its safety and shows low potential for abuse in humans. It is generally considered safe, with no significant withdrawal symptoms observed in animal studies, and it has been used to improve sleep and reduce opioid withdrawal symptoms in clinical settings. ^{1 2 3 4 5}

How does the drug Suvorexant differ from other treatments for opioid use disorder?

Suvorexant is unique because it is primarily used as a sleep aid, working by blocking orexin receptors in the brain, which is different from traditional opioid use disorder treatments like buprenorphine that target opioid receptors directly. ^{6 7 8 9 10}

Research Team

Andrew S Huhn, Ph.D.

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for adults aged 18-65 with opioid use disorder, specifically those who have used fentanyl recently. Participants must be interested in buprenorphine treatment for their condition and able to follow the study's rules. They should not have significant medical conditions that could interfere with the trial, nor plans to move away during the study period.

Inclusion Criteria

Meets DSM-5 criteria for opioid use disorder (OUD) with evidence of physical dependence on opioids

Willing to comply with study protocol

Plans to reside in current area for study period

Exclusion Criteria

I have narcolepsy, restless leg syndrome, or sleep paralysis.

Urine sample testing positive for benzodiazepine at screening and admission to residential treatment

Have circumstances that would interfere with study participation (e.g., impending jail)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Residential Phase

Participants are stabilized on sublingual buprenorphine/naloxone and receive suvorexant or placebo

5 days

Residential stay

Outpatient Phase

Participants are maintained on sublingual buprenorphine/naloxone and transitioned to extended-release buprenorphine

3 weeks

Regular outpatient visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo
• Suvorexant

Trial Overview The trial tests if suvorexant helps people with opioid use disorder when added to buprenorphine therapy compared to a placebo. It starts with a 5-day stay where participants stabilize on buprenorphine/naloxone, followed by a 3-week outpatient phase including extended-release buprenorphine.

Participant Groups

Group I: Suvorexant Experimental Treatment 1 Intervention

Nightly dosing of suvorexant

Group II: Placebo Placebo Group 1 Intervention

Nightly dosing of placebo

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

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]

Suvorexant, a drug that blocks orexin receptors and is typically used for insomnia, shows potential in reducing oxycodone-seeking behavior in rats, particularly after a period of withdrawal, suggesting it could be repurposed for treating prescription opioid use disorder (OUD).

While suvorexant did not significantly reduce overall oxycodone self-administration, it effectively decreased drug-seeking behavior during the first hour of testing and blocked reinstatement of seeking behavior, especially in male rats, indicating its potential efficacy in managing cravings associated with OUD.

NCBI (Pubmed)

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. Illenberger, JM., Flores-Ramirez, FJ., Matzeu, A., et al.[2023]

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, the first dual orexin receptor antagonist approved for sleep disorders, is metabolized primarily by four cytochrome P450 enzymes (3A4, 2C19, 2D6, and 2C9), which is important for understanding its pharmacokinetics and potential interactions with other drugs.

In forensic investigations, the hydroxylated metabolite of suvorexant (M9) was identified in blood samples from 12 medicolegal death cases and one impaired driving case, highlighting its relevance in toxicology and the need for further studies on its effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CYP450-Mediated metabolism of suvorexant and investigation of metabolites in forensic case specimens. Skillman, B., Kerrigan, S.[2021]

In a 14-day study involving 150 opioid-dependent patients, buprenorphine was found to be more effective than placebo, as patients on buprenorphine had longer time on their initial dose, requested fewer dose changes, and used less illicit opioids.

The study highlights that buprenorphine, a mu-opioid partial agonist, is not only effective in reducing opioid use but also well-accepted by patients, making it a promising treatment option for opioid dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A placebo controlled clinical trial of buprenorphine as a treatment for opioid dependence. Johnson, RE., Eissenberg, T., Stitzer, ML., et al.[2019]

In normal rhesus monkeys, beta-funaltrexamine (beta-FNA) caused muscle relaxation and stupor, effects that could be reversed by the opioid antagonist Win 44,441, indicating its potential agonist properties.

In morphine-dependent monkeys, beta-FNA triggered severe withdrawal symptoms, demonstrating its strong potency as an opioid antagonist, particularly when administered directly into the brain, being over 13,000 times more effective than subcutaneous administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of beta-funaltrexamine in normal and morphine-dependent rhesus monkeys: observational studies. Gmerek, DE., Woods, JH.[2013]

The lead compound MP1104, an analog of 3-Iodobenzoyl naltrexamine (IBNtxA), demonstrated 15 times greater pain-relieving potency than morphine, acting through kappa- and delta-opioid receptors.

Importantly, MP1104 did not induce aversion or preference in mice, suggesting a lower risk of addiction compared to traditional opioids, while also showing potential to reduce cocaine-related reward behavior.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and characterization of a dual kappa-delta opioid receptor agonist analgesic blocking cocaine reward behavior. Váradi, A., Marrone, GF., Eans, SO., et al.[2019]

In a study of 60 chronic alcoholics treated with metadoxine for 30 days, significant reductions in abstinence symptoms such as anxiety, depression, and insomnia were observed compared to a placebo group.

Metadoxine not only decreased the need for additional medications like benzodiazepines but also helped in maintaining abstinence from alcohol in the short term, indicating its potential as an effective treatment for alcohol dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapeutic use of metadoxine in chronic alcoholism. Double blind study of patients in a department of general medicine]. Rizzo, A., Breda, A., Moretto, F., et al.[2015]

Higher doses of buprenorphine (BUP) significantly decrease mu-opioid receptor (muOR) availability in the brain, with reductions of 41% to 84% observed at doses of 2 mg to 32 mg, respectively, indicating a strong dose-dependent effect.

The study found that as muOR availability decreased, plasma levels of BUP and its metabolite nor-BUP increased, which correlated with reduced withdrawal symptoms and diminished responses to hydromorphone, suggesting that effective opioid maintenance therapy can be achieved through high-dose BUP administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of buprenorphine maintenance dose on mu-opioid receptor availability, plasma concentrations, and antagonist blockade in heroin-dependent volunteers. Greenwald, MK., Johanson, CE., Moody, DE., et al.[2022]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

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

3. 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]

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

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

5. Ireland pubmed.ncbi.nlm.nih.gov

CYP450-Mediated metabolism of suvorexant and investigation of metabolites in forensic case specimens. [2021]

6. Ireland pubmed.ncbi.nlm.nih.gov

A placebo controlled clinical trial of buprenorphine as a treatment for opioid dependence. [2019]

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

Effects of beta-funaltrexamine in normal and morphine-dependent rhesus monkeys: observational studies. [2013]

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

Synthesis and characterization of a dual kappa-delta opioid receptor agonist analgesic blocking cocaine reward behavior. [2019]

9. Italy pubmed.ncbi.nlm.nih.gov

[Therapeutic use of metadoxine in chronic alcoholism. Double blind study of patients in a department of general medicine]. [2015]

10. England pubmed.ncbi.nlm.nih.gov

Effects of buprenorphine maintenance dose on mu-opioid receptor availability, plasma concentrations, and antagonist blockade in heroin-dependent volunteers. [2022]