Buprenorphine for Opioid Use Disorder

Overseen By Joji Suzuki, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Brigham and Women's Hospital

Must not be taking: Opioids, CYP34A inducers

Disqualifiers: Substance use disorder, Chronic pain, 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: 3

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests different doses of buprenorphine, a medication for opioid use disorder, to understand its effects in the body. Participants will receive the medication in three ways: a low dose through an IV and two higher doses taken orally. The goal is to observe how the body processes buprenorphine and ensure its safety for further studies. Suitable candidates for this trial include individuals who have used opioids in the past year but are currently in good physical health and not using drugs or alcohol. As a Phase 1 trial, this research aims to understand how the treatment works in people, allowing participants to contribute to the foundational knowledge of buprenorphine's effects.

Do I need to stop taking my current medications for the trial?

The trial requires that you do not take certain medications, specifically those that are strong or moderate CYP34A inducers or inhibitors, in the past 30 days. If you are on such medications, you may need to stop them before participating.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that buprenorphine is generally safe for people. The FDA has approved medications with buprenorphine since 2002 to treat opioid dependence, indicating its safety. Although specific data for the IV form is lacking, tests on healthy volunteers suggest it is expected to be safe.

For the oral form, studies confirm its effectiveness in treating opioid use disorder. However, warnings exist about dental problems with the type that dissolves in the mouth. Despite this, the benefits of buprenorphine seem to outweigh these risks, and good oral hygiene can help manage them.

In summary, both the IV and oral forms of buprenorphine are considered safe based on past approvals and studies. However, it is important to be aware of possible side effects, such as dental issues with the oral form. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about buprenorphine for opioid use disorder because it offers a unique approach to treatment. Unlike some standard options like methadone or naltrexone, buprenorphine is a partial opioid agonist, meaning it can reduce cravings and withdrawal symptoms without producing the same high as full agonists. This property makes it safer and less addictive. Additionally, the trial explores varying doses and administration methods, like an initial 0.15mg IV dose followed by 8mg and 16mg oral doses, to optimize effectiveness and convenience for patients. These features could offer improved outcomes and flexibility over current treatments.

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

Research has shown that buprenorphine effectively treats opioid addiction. Studies have found that it helps reduce opioid use and outperforms detox alone in improving recovery. Buprenorphine is also linked to fewer overdoses and serious health issues related to opioids. In this trial, participants will receive varying dosages of buprenorphine, including a 0.15mg IV dose and oral doses of 8mg or 16mg, to assess its effectiveness. When taken as directed, many patients either stop using opioids or significantly reduce their use. Overall, buprenorphine is a well-supported treatment option for managing opioid addiction. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for English-speaking adults over 18 with a history of opioid use, either prescribed or not, in the past year. They must have stable vital signs and be in good health as confirmed by medical exams, lab tests, and EKG. It's not suitable for those outside these criteria.

Inclusion Criteria

Your heart rate, blood pressure, and breathing rate should be within certain normal ranges before starting the trial.

You have used opioids before, whether for medical reasons or not.

I am in good health as confirmed by recent medical exams.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive buprenorphine in 3 separate inpatient 2-night visits, with doses of 0.15mg IV, 8mg PO, or 16mg PO, at least 1 week apart.

6 weeks

3 visits (inpatient)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Buprenorphine

Trial Overview The study is testing low-dose buprenorphine induction strategies on healthy volunteers to manage opioid dependence. Participants will receive different doses of buprenorphine across three sessions with naltrexone to prevent dependency.

How Is the Trial Designed?

Group I: 8mg PO buprenorphine Experimental Treatment 1 Intervention

After the open-label period, the participant will receive 8mg PO, then 16mg PO will be administered in the following visit.

Group II: 16mg PO buprenorphine Experimental Treatment 1 Intervention

After the open-label period, the participant will receive 16mg PO, then 8mg PO will be administered in the following visit.

Group III: 0.15mg IV Dose Experimental Treatment 1 Intervention

The first dose administered will be fixed to an open-label 0.15mg IV dose.

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?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

University of Utah

Collaborator

Trials

1,169

Recruited

1,623,000+

Published Research Related to This Trial

Buprenorphine is a safe and effective treatment for opioid dependence, particularly when combined with naloxone, which reduces its potential for abuse.

New regulations enable certified physicians to prescribe buprenorphine in their offices, significantly improving patient access to this important treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine maintenance: a new treatment for opioid dependence. Collins, GB., McAllister, MS.[2019]

A study analyzing 5,970 emergency department visits in Italy found that benzodiazepines (BZD) and Z-drugs (ZD) are associated with a higher rate of adverse events (AEs) leading to hospitalization compared to opioids, particularly among younger patients and those with a history of substance abuse.

23% of BZD/ZD-related AEs were linked to drug abuse, and these cases often required hospitalization (52%), highlighting the significant health risks associated with the inappropriate use of these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hospitalisations related to benzodiazepine, Z-drug, and opioid treatment in Italy: a claim on the risks associated with inappropriate use. Mattioli, I., Bettiol, A., Crescioli, G., et al.[2022]

Zoledronic acid (ZOL), administered as a single intravenous infusion once a year, effectively reduces the risk of vertebral and hip fractures in postmenopausal women with osteoporosis, and also lowers the incidence of future fractures in men and women with recent hip fractures.

ZOL is generally safe and well tolerated, with mild and transient flu-like symptoms occurring after the first infusion, making it a convenient option for patients who may struggle with compliance to oral bisphosphonates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zoledronic acid for prevention and treatment of osteoporosis. Recknor, C.[2018]

Intravenous zoledronic acid (Zol) is effective in reducing fracture risk in patients with postmenopausal osteoporosis and recent low-trauma hip fractures, showing improvements in bone mineral density and early reduction of bone remodeling markers.

Zol is generally well tolerated and offers a convenient once-a-year treatment option, making it suitable for older patients with adherence issues to oral medications, although it is not recommended for those with severe renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of zoledronic acid in the prevention and treatment of osteoporosis. Räkel, A., Boucher, A., Ste-Marie, LG.[2023]

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]

Buprenorphine and its combination with naloxone (Suboxone) have been officially added to the list of approved medications for treating opioid dependence in federally certified treatment programs, alongside methadone and ORLAAM.

These medications will be subject to the same federal treatment standards as existing opioid treatments, ensuring consistent safety and efficacy protocols in managing opioid dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opioid drugs in maintenance and detoxification treatment of opiate addiction; addition of buprenorphine and buprenorphine combination to list of approved opioid treatment medications. Interim final rule. [2013]

A study of 200 rural residents revealed that motivations for using nonprescribed buprenorphine shifted from initially seeking to avoid withdrawal and get high to maintaining abstinence from other drugs, indicating a complex relationship with self-treatment.

Participants with a history of treatment for opioid use disorder were more likely to use nonprescribed buprenorphine for self-treatment, suggesting that dissatisfaction with existing treatment options may drive individuals to seek alternatives outside of prescribed care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing Motivations for Nonprescribed Buprenorphine Use Among Rural Appalachian Substance Users. McDonald, MJ., DeVeaugh-Geiss, AM., Chilcoat, HD., et al.[2023]

In a study of 32 veterans over three years, those receiving buprenorphine/naloxone in a group setting had a significantly higher retention rate in treatment after one year (69%) compared to those treated individually (27%).

The study also found that 94% of urine samples from participants were negative for opioids, indicating effective management of opioid use disorder with buprenorphine/naloxone in a group format.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Group medication management for buprenorphine/naloxone in opioid-dependent veterans. Berger, R., Pulido, C., Lacro, J., et al.[2014]

Buprenorphine, approved for treating opiate dependence, has been found to have an abuse potential similar to that of traditional opioids like morphine, despite initial beliefs of its low abuse risk.

A study of 120 buprenorphine abusers revealed that the majority were middle-aged males with a significant history of early illicit drug use, highlighting a concerning trend of prescription medication abuse that requires increased awareness and vigilance among healthcare professionals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Socio-demographic profile and help-seeking behaviour of buprenorphine abusers in Singapore. Winslow, M., Ng, WL., Mythily, S., et al.[2020]

Suboxone (buprenorphine/naloxone) is a well-tolerated and effective treatment for opiate addiction, with significant positive psychological and behavioral changes observed in patients during the first month of therapy.

The initial phase of treatment is critical, as nearly 22.5% of patients dropped out within the first month, highlighting the need for thorough patient education about potential withdrawal symptoms to improve retention rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early experience with Suboxone maintenance therapy in Hungary. Demetrovics, Z., Farkas, J., Csorba, J., et al.[2015]

Chronic use of intravenous bisphosphonates, like Zometa, can lead to bisphosphonate-related osteonecrosis of the jaws (BRONJ), which is a serious and painful condition that can have severe consequences for patients.

This case highlights the importance for dentists to recognize the early signs of BRONJ and consider treatment options, including conservative measures and potential jaw resection, to manage this complication effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bisphosphonate-related osteonecrosis of the jaws--a case report. Kamoh, AK., Ogle, O.[2018]

Buprenorphine is an opioid medication used for treating opioid dependence and managing moderate to severe pain, and it can be prescribed to pregnant women as part of their treatment for opioid addiction.

The chapter details a method for quantifying buprenorphine and its metabolite norbuprenorphine in meconium using liquid chromatography tandem mass spectrometry (LC-MS/MS), which is important for monitoring drug exposure in newborns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitation of Total Buprenorphine and Norbuprenorphine in Meconium by LC-MS/MS. Marin, SJ., McMillin, GA.[2016]

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 (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]

Citations

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Buprenorphine Treatment for Opioid Use Disorder Among all randomized patients, buprenorphine was modestly superior to XR-naltrexone on the primary outcome of relapse, and on the number of opioid positive ...

2. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK459126/

Buprenorphine - StatPearls - NCBI Bookshelf Buprenorphine use has proven to be more effective than detoxification in enhancing outcomes for individuals with opioid dependence. When compared to ...

3. 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 ...

4. cda-amc.ca cda-amc.ca/sites/default/files/pdf/htis/2024/RE0051-Buprenorphine-Formulations.pdf

Buprenorphine Formulations for Opioid Use Disorder This rapid review examines their relative clinical effectiveness, safety, and cost-effectiveness and offers an overview of their use in.

5. recoveryanswers.org recoveryanswers.org/research-post/better-down-the-road-the-long-term-outcomes-of-opioid-use-disorder-patients-treated-with-medication/

Better Down the Road? The Long-term Outcomes of Opioid ... Research has shown that medications such as methadone and buprenorphine/naloxone (“Suboxone”) are effective at reducing opioid use.

6. samhsa.gov samhsa.gov/

Home | SAMHSA - Substance Abuse and Mental Health ... SAMHSA leads efforts to advance behavioral health across the U.S., offering resources for mental health, substance use, and community well-being.

7. brixadi.com brixadi.com/

Home | BRIXADI® (buprenorphine) extended-release ... FDA-approved BRIXADI is a prescription medicine for opioid addiction, also called opioid use disorder (OUD). Please see Prescribing Information, ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2772724623000033

History of the discovery, development, and FDA-approval ... Buprenorphine-based medications were first approved by the United States Food and Drug Administration in 2002 for the treatment of opioid dependence.

9. fda.gov fda.gov/news-events/press-announcements/fda-approves-new-buprenorphine-treatment-option-opioid-use-disorder

FDA Approves New Buprenorphine Treatment Option for ... The US Food and Drug Administration approved Brixadi (buprenorphine) extended-release injection for subcutaneous use (under the skin) to treat moderate to ...