Buprenorphine Formulations for Opioid Use Disorder

Overseen By John Mariani, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Rachel R. Luba

Must not be taking: Methadone, Sedative-hypnotics, Alcohol, others

Disqualifiers: Other substance use disorder, unmanaged psychiatric, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 13

Duration: 12 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two forms of buprenorphine, a medication for opioid use disorder, particularly for those using fentanyl or similar opioids. It compares a long-acting injectable version with the standard sublingual (under-the-tongue) version to determine which more effectively reduces drug use and prevents relapse. Participants will begin treatment with an overnight hospital stay and will attend follow-up visits to monitor their progress. The trial seeks individuals who regularly use fentanyl or similar opioids and are seeking treatment for opioid use disorder. As an Early Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to contribute to groundbreaking research in opioid use disorder treatment.

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've used medications or herbal products that affect liver enzymes (CYP3A4) in the past 30 days.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that injectable buprenorphine is generally well-tolerated by patients with opioid use disorder. Research found that only a small percentage of people stopped using the treatment due to side effects, suggesting that most can handle it without major issues. Some experienced mild to moderate side effects, but these rarely led to discontinuation.

For those taking sublingual buprenorphine, placed under the tongue, similar safety results have been observed. As a standard treatment for opioid use disorder, it has been widely used and is generally considered safe.

In both treatments, the most common side effects might include headaches or nausea, but these are often manageable. Both forms of buprenorphine have been studied in various settings and have shown promising safety records for those dealing with opioid use disorder. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for opioid use disorder because they offer new ways to deliver buprenorphine, a medication already used to manage this condition. Unlike traditional sublingual tablets, the long-acting injectable buprenorphine provides a sustained release, potentially reducing the need for daily dosing and improving adherence. This could make treatment more convenient and effective for patients. The sublingual buprenorphine/naloxone combination remains a standard of care, but the injectable form is particularly promising for those who struggle with taking medication daily.

What evidence suggests that this trial's treatments could be effective for opioid use disorder?

Studies have shown that buprenorphine effectively treats opioid use disorder by reducing cravings and withdrawal symptoms, making it easier for individuals to stop using opioids like fentanyl. Research indicates that injectable buprenorphine, one of the treatments in this trial, can improve health and lower the risk of overdose. Additionally, using buprenorphine or similar medications can reduce death rates by about 50%, resulting in fewer opioid-related deaths. This trial will compare the effectiveness of both the under-the-tongue (sublingual) and injectable forms to determine which works better for different individuals. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals aged 18-65 with opioid use disorder, specifically those using fentanyl or similar potent synthetic opioids. Participants must be willing to stay overnight in a hospital for initial treatment and provide blood and urine samples. Follow-up visits are required.

Inclusion Criteria

Meets DSM-5 criteria for OUD with at least moderate severity

Voluntarily seeking treatment for opioid use disorder (OUD)

I regularly use fentanyl or similar strong painkillers.

Exclusion Criteria

Liver function tests > 2x the upper limit of normal

I have been treated with buprenorphine or methadone in the last 30 days.

Known allergy, hypersensitivity or intolerance to buprenorphine

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants complete a brief overnight hospital stay to start treatment with either sublingual or injectable buprenorphine

1 day

1 visit (inpatient)

Treatment

Participants receive either sublingual buprenorphine or injectable buprenorphine and provide blood and urine samples

12 weeks

6 visits (in-person)

Follow-up

Participants are monitored for drug use, craving, withdrawal, quality of life, and physical health

12 weeks

6 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Buprenorphine

Trial Overview

The study compares sublingual buprenorphine (Suboxone) with long-acting injectable buprenorphine to see which is better at reducing drug use and preventing relapse in opioid users. It also examines how body factors and early treatment levels affect outcomes.

How Is the Trial Designed?

Group I: Injectable Buprenorphine Experimental Treatment 1 Intervention

Long-Acting Injectable Buprenorphine administered after participants receive and tolerate a single 4/1 mg sublingual buprenorphine/naloxone dose

Group II: Sublingual Buprenorphine/Naloxone Active Control 1 Intervention

Titration onto sublingual buprenorphine/naloxone (standard of care)

Buprenorphine is already approved in United States, European Union for the following indications:

Approved in United States as Buprenorphine for:

• Moderate to severe opioid addiction (dependence)

Approved in European Union as Buprenorphine for:

• Opioid dependence

Who Is Running the Clinical Trial?

Rachel R. Luba

Lead Sponsor

Trials

1

Recruited

60+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

The novel weekly subcutaneous buprenorphine depot formulation, CAM2038, was found to effectively block the euphoric effects of opioids and suppress withdrawal symptoms in individuals with moderate-to-severe opioid use disorder, based on a study involving 47 participants.

Both doses of CAM2038 (24 mg and 32 mg) were well-tolerated and demonstrated significant efficacy in preventing opioid effects, making it a promising alternative to daily oral formulations that carry risks of misuse and nonadherence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Buprenorphine Weekly Depot (CAM2038) and Hydromorphone Blockade in Individuals With Opioid Use Disorder: A Randomized Clinical Trial. Walsh, SL., Comer, SD., Lofwall, MR., et al.[2020]

Buprenorphine plus naloxone (Suboxone) is marketed as having a lower risk of abuse compared to buprenorphine alone (Subutex), but evidence supporting this claim is lacking, as noted in a review of the literature.

Transitioning from buprenorphine alone to the combination of buprenorphine/naloxone has not shown a decrease in risky behaviors, such as injection drug use among individuals with opioid dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comment on "a comparison of buprenorphine + naloxone to buprenorphine and methadone in the treatment of opioid dependence during pregnancy: maternal and neonatal outcomes". Newman, RG., Gevertz, SG.[2021]

In a study involving 24 participants with opiate dependence, the 16 mg buprenorphine tablet formulation achieved higher serum concentrations than the 8 mg liquid solution by Day 7, indicating better pharmacokinetics for the tablet.

Despite the higher serum concentration, there were no significant differences in the physiological, subjective, or objective effects of the two formulations, suggesting that clinicians may need to adjust dosing for the tablet to achieve similar effects as the liquid solution.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, bioavailability and opioid effects of liquid versus tablet buprenorphine. Compton, P., Ling, W., Moody, D., et al.[2013]

In a study of 255,726 Veterans with opioid use disorder (OUD), 15.8% received buprenorphine medication treatment (B-MOUD), with a significant increase in treatment courses over time, from 1550 in 2007 to 8146 in 2018.

Patients receiving B-MOUD had a median treatment duration of 157 days, with 33.8% undergoing multiple treatment courses, indicating that B-MOUD is a commonly utilized and persistent treatment option for managing OUD in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine use and courses of care for opioid use disorder treatment within the Veterans Health Administration. Gordon, AJ., Saxon, AJ., Kertesz, S., et al.[2023]

A study analyzing abuse trends of sublingual buprenorphine products from 2003 to 2005 found that Subutex accounted for only 7.8% of reported abuse cases, while Suboxone made up 92.2%.

The overall rate of abuse for both products was low, with an average quarterly abuse rate of 0.08 cases per 1,000 prescriptions for Subutex and 0.16 for Suboxone, indicating that these medications are relatively safe in terms of abuse potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abuse of buprenorphine in the United States: 2003-2005. Smith, MY., Bailey, JE., Woody, GE., et al.[2013]

A study involving 53 opioid-dependent patients showed that switching from buprenorphine to buprenorphine/naloxone was well-tolerated, with no significant issues reported during the transition.

Patients expressed a preference for buprenorphine/naloxone over buprenorphine, with 54% favoring the combination formulation due to its taste and ease of use, indicating it may be a more acceptable option for maintenance treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preference for buprenorphine/naloxone and buprenorphine among patients receiving buprenorphine maintenance therapy in France: a prospective, multicenter study. Daulouède, JP., Caer, Y., Galland, P., et al.[2015]

Buprenorphine (Subutex) is recognized for its improved safety profile in treating opioid dependence, particularly by reducing the risk of overdose compared to other opioids.

Despite its safety advantages, there are still risks associated with the diversion of buprenorphine for misuse, as evidenced by cases of attempted intravenous injection, highlighting the need for strict dispensing protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Groin tissue necrosis requiring skin graft following parenteral abuse of buprenorphine tablets. Feeney, GF., Fairweather, P.[2013]

Buprenorphine is a versatile medication designed for both pain relief and treatment of opioid use disorder, acting as a partial agonist at mu receptors and an antagonist at delta receptors, which helps manage pain while reducing the risk of misuse.

Various formulations of buprenorphine, including injectable, transdermal, and sublingual options, have been developed to cater to different patient needs, with specific combinations like Suboxone® including naloxone to deter misuse in opioid dependence treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine and its formulations: a comprehensive review. Poliwoda, S., Noor, N., Jenkins, JS., et al.[2022]

Buprenorphine, particularly the brand-name formulations like Suboxone, has been significantly more utilized and reimbursed in Medicaid compared to other formulations, with brand-name versions dispensed 2.7 times more and costing 4.4 times more than all other formulations combined from 2002 to 2018.

Delays in the availability of generic buprenorphine formulations due to market and regulatory factors contributed to increased costs and may have hindered access to treatment for opioid use disorder during the opioid crisis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors Affecting Buprenorphine Utilization and Spending in Medicaid, 2002-2018. Barenie, RE., Sinha, MS., Kesselheim, AS.[2021]

The study will involve 280 adults with opioid use disorder and aims to improve adherence to buprenorphine-naloxone treatment through two psychological interventions: contingency management (CM) and brief motivational interviewing plus substance-free activities and mindfulness (BSM).

The primary goal is to assess which intervention is more effective in promoting medication adherence, measured by attendance at physician appointments and the presence of buprenorphine in urine toxicology, with follow-up occurring 8 months after randomization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of a sequential multiple assignment randomized trial to test contingency management and an integrated behavioral economic and mindfulness intervention for buprenorphine-naloxone medication adherence for opioid use disorder. Peter, SC., Murphy, JG., Witkiewitz, K., et al.[2023]

In a study of 313 opioid-dependent adults, the sublingual buprenorphine/naloxone rapidly dissolving tablet was found to be less effective than generic buprenorphine for treatment retention at day 3, with 88.3% retention compared to 95.3% for generic buprenorphine.

Despite the lower retention rate, both treatments showed similar effectiveness in reducing withdrawal symptoms and cravings, indicating that buprenorphine/naloxone is generally safe and can still help manage withdrawal despite not being non-inferior to generic buprenorphine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of a sublingual buprenorphine/naloxone rapidly dissolving tablet for the treatment of adults with opioid dependence: A randomized trial. Webster, L., Hjelmström, P., Sumner, M., et al.[2017]

Citations

1.

jamanetwork.com

jamanetwork.com/journals/jamanetworkopen/fullarticle/2820859

Extended-Release 7-Day Injectable Buprenorphine for ...

Meaning Results of this study suggest that 7-day extended-release buprenorphine may be feasible in patients with opioid use disorder presenting ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11836814/

Investigating outcomes in a substance use treatment provider

Research has demonstrated that treatment with opioid agonist medications such as methadone or buprenorphine reduces mortality by around 50% in ...

3.

recoveryanswers.org

recoveryanswers.org/research-post/injectable-buprenorphine-1-year-outcomes/

Injectable buprenorphine for opioid use disorder: Effects on ...

The current study examined the effects of injectable buprenorphine on 12-month patient-centered outcomes. Patients reported improvements in health status, ...

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S0376871625002510

Extended-release injectable buprenorphine for the ...

This prospective clinical cohort study found that among 25 patients with OUD at high risk of overdose who started XR-BUP in were followed in a low-barrier ...

5.

cdc.gov

cdc.gov/mmwr/volumes/73/wr/mm7325a1.htm

Treatment for Opioid Use Disorder: Population Estimates

Medications for opioid use disorder (OUD), particularly buprenorphine and methadone, substantially reduce overdose-related and overall mortality ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12125644/

Initiating Injectable Buprenorphine in People Hospitalized ...

Efficacy and safety of a monthly buprenorphine depot injection for opioid use disorder: a multicentre, randomised, double-blind, placebo ...

7.

brixadihcp.com

brixadihcp.com/safety/

Clinical Safety Profile

Adverse reactions led to premature discontinuation in 10 (4.7%) patients in the group receiving BRIXADI compared to 5 (2.3%) patients in the sublingual ...