Extended Release Buprenorphine for Opioid Use Disorder

(EXHITENTRE Trial)

Recruiting at 5 trial locations

Overseen By Zoe Weinstein, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Hennepin Healthcare Research Institute

Must be taking: Buprenorphine

Must not be taking: Methadone, Extended-release opioids

Disqualifiers: Severe alcohol use, Severe benzodiazepine use, Terminal diagnosis, Liver disease, Pregnancy, others

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

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

Compensation: Varies

Number of Visits: 34

Duration: 28 days

344 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new 28-day extended-release version of buprenorphine, a medication for opioid use disorder (OUD), to compare its effectiveness with usual treatments like methadone or naltrexone. The goal is to determine if this new formulation can help individuals with moderate or severe OUD better manage their condition after hospital discharge. Participants will either receive the new buprenorphine injection or continue with standard treatments before discharge. Suitable candidates are hospitalized individuals diagnosed with moderate or severe OUD who are open to starting medication for their condition. As a Phase 2, Phase 3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in OUD treatment.

Do I have to stop taking my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you have taken a long-acting opioid other than buprenorphine in the three days before randomization or if you have received maintenance MOUD in the 14 days before hospitalization.

Will I have to stop taking my current medications?

The trial requires that participants not be taking long-acting opioids other than buprenorphine in the three days before randomization. If you are on such medications, you may need to stop them before joining the trial.

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

Research has shown that extended-release buprenorphine (XR-BUP) is generally safe for people with opioid use disorder (OUD). One study found that although not everyone remained in treatment for six months, most participants tolerated it well, even those at high risk of overdose. Another study found that people using XR-BUP had fewer hospital and emergency room visits compared to those on other treatments, suggesting it might be a safer choice in everyday situations. Overall, these findings indicate that XR-BUP is considered safe for people with OUD. ^{1 2 3 4 5}

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

Researchers are excited about extended-release buprenorphine for opioid use disorder because it offers a unique delivery method, providing a single subcutaneous injection that lasts 28 days. Unlike other treatments such as methadone, sublingual buprenorphine, or naltrexone, which often require daily dosing, this extended-release form could improve adherence by reducing the burden of daily medication. This approach also ensures a consistent therapeutic effect, potentially minimizing the risk of relapse during the critical period following hospital discharge.

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

Research has shown that extended-release buprenorphine (XR-BUP), which participants in this trial may receive, effectively treats opioid use disorder (OUD). One study found that XR-BUP helped more people remain opioid-free compared to those on daily oral treatments. Another study demonstrated that XR-BUP was more effective in preventing relapse than some other treatments. Additionally, only a small number of patients experienced withdrawal symptoms after switching to XR-BUP, indicating it is generally well-tolerated. These findings suggest that XR-BUP can be a strong option for managing OUD. Meanwhile, another group in this trial will receive Treatment as Usual, which includes community standard care such as methadone, sublingual buprenorphine, or naltrexone. ^{1 3 6 7 8}

Who Is on the Research Team?

Gavin Bart, MD,PhD

Principal Investigator

Hennepin Heatlhcare

Are You a Good Fit for This Trial?

This trial is for adults over 18 with moderate or severe opioid use disorder who are hospitalized and willing to start medication treatment. They must speak English well enough for consent and not have serious medical conditions that could interfere with the study or make it unsafe.

Inclusion Criteria

Meet Diagnostic and Statistical Manual (DSM-5) criteria for moderate or severe OUD

I am willing to start medication-assisted treatment, including buprenorphine.

I am currently in the hospital.

Exclusion Criteria

I have a severe alcohol or benzodiazepine addiction that can't be treated quickly.

I have been on medication for opioid use disorder up to 14 days before being hospitalized.

Currently pregnant

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

During hospitalization

Treatment

Participants receive either a single injection of extended-release buprenorphine or treatment as usual within 72 hours of anticipated hospital discharge

28 days

Follow-up

Participants are monitored for engagement in OUD treatment and adverse events

180 days

Assessments at 34, 90, and 180 days post discharge

What Are the Treatments Tested in This Trial?

Interventions

• Extended Release Buprenorphine
• Treatment as Usual

Trial Overview The study compares a new 28-day extended-release buprenorphine (XR-BUP) with usual treatments in patients seen by an addiction service at the hospital. Participants will be randomly assigned to either XR-BUP or standard care before leaving the hospital, followed up after discharge.

How Is the Trial Designed?

Group I: Interventional Experimental Treatment 1 Intervention

Single subcutaneous injection of a 28-day formulation of extended-release buprenorphine within 72 hours of anticipated hospital discharge.

Group II: Treatment as Usual Active Control 1 Intervention

Community standard of care that includes initiation of either methadone, sublingual (SL) buprenorphine, or naltrexone prior to hospital discharge.

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

Approved in United States as Brixadi for:

• Moderate to severe opioid use disorder

Approved in European Union as Buvidal for:

• Opioid dependence

Approved in United States as Sublocade for:

• Moderate to severe opioid use disorder

Who Is Running the Clinical Trial?

Hennepin Healthcare Research Institute

Lead Sponsor

Trials

94

Recruited

77,100+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

The Emmes Company, LLC

Industry Sponsor

Trials

149

Recruited

1,052,000+

Peter Ronco

The Emmes Company, LLC

Chief Executive Officer since 2023

BSc from Nottingham University

Dr. Joe Sliman

The Emmes Company, LLC

Chief Medical Officer since 2020

MD from Uniformed Services University of the Health Sciences, MPH from Johns Hopkins University, BSc in Molecular and Cell Biology from Pennsylvania State University

Published Research Related to This Trial

Two case studies of pregnant patients with opioid use disorder (OUD) who switched from sublingual buprenorphine to monthly injections of Sublocade® showed no adverse outcomes for either the mothers or their babies, suggesting potential safety in this treatment during pregnancy.

Both patients maintained positive urine drug screens for buprenorphine throughout their pregnancies without experiencing withdrawal symptoms or birth anomalies, indicating that Sublocade may be a viable option for managing OUD in pregnant women, although further research is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous Extended-Release Buprenorphine Use in Pregnancy. Towers, CV., Deisher, H.[2022]

In a study involving 314 participants, monthly extended-release buprenorphine (BUP-XR) was found to be clinically superior to standard-of-care treatments, leading to an average of 123.43 days of abstinence from opioids compared to 104.37 days with standard treatments.

While BUP-XR had a higher incidence of mild to moderate adverse events, it showed a comparable safety profile overall, and was particularly more effective and cost-effective for participants with more severe opioid use disorder or those in treatment for over 28 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Superiority and cost-effectiveness of monthly extended-release buprenorphine versus daily standard of care medication: a pragmatic, parallel-group, open-label, multicentre, randomised, controlled, phase 3 trial. Marsden, J., Kelleher, M., Gilvarry, E., et al.[2023]

In a study of 533 participants over 18 months after stopping extended-release buprenorphine injection (BUP-XR), 47% reported sustained opioid abstinence, with higher rates of abstinence linked to longer treatment durations.

More than 60% of participants showed stable or improved outcomes in health-related quality of life and mental health scores, indicating that BUP-XR has a long-term positive impact on recovery from opioid use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continued Posttrial Benefits of Buprenorphine Extended Release: RECOVER Study Findings. Boyett, B., Nadipelli, VR., Solem, CT., et al.[2023]

New prolonged-release formulations of buprenorphine, including a six-month implant and two subcutaneous injection depots, aim to improve patient comfort and safety by reducing the need for daily intake and minimizing risks associated with sublingual forms.

These formulations have shown promise in addressing concerns about treatment adherence, particularly for stabilized patients, while also raising some apprehensions about potential coercive use among opioid users.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged-release buprenorphine formulations: Perspectives for clinical practice]. Chappuy, M., Trojak, B., Nubukpo, P., et al.[2022]

New prolonged-release formulations of buprenorphine, including a six-month implant and two subcutaneous injection depots, aim to improve patient comfort and safety by reducing the need for daily intake and minimizing risks associated with sublingual forms.

These formulations have shown promise in addressing concerns about treatment adherence, particularly for stabilized patients, while also raising some apprehensions about potential coercive use among opioid users.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged-release buprenorphine formulations: Perspectives for clinical practice. Chappuy, M., Trojak, B., Nubukpo, P., et al.[2021]

In a study involving adults with moderate-to-severe opioid use disorder (OUD), the 300-mg maintenance dose of BUP-XR (SUBLOCADE®) was found to be more effective than the 100-mg dose for opioid-injecting participants, leading to better treatment retention and higher rates of opioid abstinence.

Both the 100-mg and 300-mg doses of BUP-XR had similar safety profiles, indicating that increasing the dose for injecting participants does not compromise safety while enhancing treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Examining the benefit of a higher maintenance dose of extended-release buprenorphine in opioid-injecting participants treated for opioid use disorder. Greenwald, MK., Wiest, KL., Haight, BR., et al.[2023]

Methadone and buprenorphine are effective first-line treatments for opioid dependence, with new long-acting formulations like CAM 2038 (Buvidal®), RBP-6000 (Sublocade™), and Probuphine™ offering innovative options for maintenance therapy.

These long-acting buprenorphine formulations provide flexibility in treatment schedules, potentially improving adherence and outcomes for individuals with opioid dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New slow-release buprenorphine formulations for optimization of opioid substitution]. Soyka, M., Pogarell, O.[2020]

In a clinical trial with 428 participants, weekly and monthly subcutaneous (SC) buprenorphine depot formulations were found to be noninferior to daily sublingual (SL) buprenorphine with naloxone in treating opioid use disorder, showing similar response rates and urine test results for opioid use.

The SC buprenorphine group demonstrated a statistically superior cumulative distribution function (CDF) for no illicit opioid use compared to the SL buprenorphine group, suggesting that depot formulations may offer additional benefits in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly and Monthly Subcutaneous Buprenorphine Depot Formulations vs Daily Sublingual Buprenorphine With Naloxone for Treatment of Opioid Use Disorder: A Randomized Clinical Trial. Lofwall, MR., Walsh, SL., Nunes, EV., et al.[2022]

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]

Citations

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Transition to Extended-release Buprenorphine Injectable ... For Bup-XR-S studies, 75 patients transitioned to Bup-XR-S within 24 hours. Of patients, 4% experienced withdrawal symptoms requiring additional ...

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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 ...

3. 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 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10398112/

Effectiveness and Value of Extended-Release Opioid ... The percentage of opioid-negative urine samples for Brixadi was 35.1% and 28.4% for buprenorphine/naloxone over 24 weeks. Based on the study's noninferiority ...

5. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00488-1/fulltext

Superiority and cost-effectiveness of monthly extended ... Evaluated against the daily oral SoC, monthly BUP-XR is clinically superior, delivering greater abstinence from opioids, longer treatment ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39543001/

A Single-Dose Study to Evaluate the Relative ... This open-label pharmacokinetic study assessed three alternative injection locations (upper arm, thigh, buttocks) to offer additional flexibility.

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK546461/

Buprenorphine extended-release injection (Sublocade ... - NCBI Key Efficacy and Safety Outcomes for Buprenorphine Extended-Release Treatment Regimens and Placebo in Patients With Opioid Use Disorder in Study 13-0001. Go ...

8. indivior.com indivior.com/en/media/press-releases/indivior-real-world-evidence-study-finds-medications-for-opioid-use-disorder-particularly-extended-release-buprenorphine-reduced-odds-of-emergency-department-visits-for-patients-with-opioid-use-disorder

Indivior Real World Evidence Study Finds Medications for ... Extended-release buprenorphine (BUP-XR) had lower rates of hospitalizations, emergency department (ED) visits, and outpatient physician office ...