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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if suvorexant, a sleep aid, can assist individuals with opioid use disorder who have recently encountered fentanyl. The study will compare suvorexant to a placebo to assess its potential to support recovery while participants stabilize and maintain on buprenorphine/naloxone, a common treatment for opioid use disorder. It suits those with opioid use disorder who test positive for fentanyl and wish to use buprenorphine to manage their condition. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group, offering participants an opportunity to contribute to significant findings.

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 there any evidence suggesting that suvorexant is likely to be safe for humans?

Research shows that suvorexant is generally safe for people with opioid use disorder (OUD). Studies have explored its use for sleep problems in this population, suggesting that suvorexant is safe and does not appear to be misused or cause harm.

The FDA has already approved suvorexant for treating insomnia, indicating it has been tested for sleep issues and found to be safe. Most participants in studies have not reported serious side effects. However, like any treatment, some side effects may occur, such as drowsiness or dizziness.

Overall, for those considering joining a trial with suvorexant, current research suggests it is safe and well-tolerated in people with OUD. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for opioid use disorder?

Unlike the standard of care for opioid use disorder, which often includes medications like methadone, buprenorphine, or naltrexone, suvorexant works through a different mechanism. Suvorexant targets the orexin system, which is involved in sleep regulation, potentially addressing sleep disturbances that are common in opioid use disorder. Researchers are excited about suvorexant because it offers a novel approach that could complement existing treatments by helping patients manage withdrawal symptoms and improve sleep quality. This unique mechanism could provide a new pathway for supporting recovery in individuals struggling with opioid dependence.

What evidence suggests that suvorexant might be an effective treatment for opioid use disorder?

Research has shown that suvorexant, which participants in this trial may receive, might aid individuals with opioid use disorder (OUD) by improving sleep. Some studies suggest it can increase total sleep time during withdrawal, potentially easing symptoms. Additionally, suvorexant may reduce cravings and stress by enhancing sleep quality. Early research indicates it might decrease the urge to seek drugs by addressing sleep issues. This trial studies the treatment's ability to ease withdrawal and support recovery in people with OUD. Participants in another arm of the trial will receive a placebo for comparison. ^{2 3 4 6 7}

Who Is on the Research Team?

Andrew S Huhn, Ph.D.

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06655883

NCT06655883 | A Study of Suvorexant (MK-4305) for the ... Researchers want to know if suvorexant will help people with OUD fall asleep and stay asleep. The goal of this study is to learn about the safety of suvorexant ...

2. reporter.nih.gov reporter.nih.gov/project-details/10454583

Evaluating Suvorexant for Sleep Disturbance in Opioid Use ... We hypothesize SUVO will improve total sleep time during withdrawal, will not show evidence of abuse liability, and will be more efficacious than trazodone.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7265392/

Repurposing the dual orexin receptor antagonist suvorexant ... Several clinical trials are currently underway to examine the efficacy of suvorexant in normalizing sleep outcomes, as well as craving, stress, and sleep ...

4. hopkinsmedicine.org hopkinsmedicine.org/news/articles/2024/12/improving-sleep-for-those-with-opioid-use-disorder

Improving Sleep for Those with Opioid Use Disorder Finding that suvorexant is safe and effective for the treatment of insomnia in people with OUD could spur the Food and Drug Administration ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0376871623001977

Preclinical Evidence Supporting the Repurposing of ... Suvorexant normalizes sleep disturbances associated with initial cocaine abstinence and facilitates the extinction of cocaine seeking behaviors.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06655883

NCT06655883 | A Study of Suvorexant (MK-4305) for the ... Researchers want to know if suvorexant will help people with OUD fall asleep and stay asleep. The goal of this study is to learn about the safety of suvorexant ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05546515

NCT05546515 | Suvorexant for Opioid/Stimulant Co-use This study will evaluate whether Suvorexant 20mg reduces drug use and craving, and improves sleep and stress among persons with co-occurring opioid use disorder ...