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

Trial Summary

What is the purpose of this trial?

This study is a multi-site open-label randomized comparative effectiveness trial of a 28-day formulation of extended-release buprenorphine (XR-BUP) versus treatment as usual (TAU) for hospitalized patients with a moderate or severe opioid use disorder (OUD) seen by an addiction consultation service (ACS) and agreeing to initiate a medication for OUD (MOUD). Participants will be randomly assigned to XR-BUP or TAU to be received within 72 hours of anticipated hospital discharge. Follow up will occur at approximately 34, 90, and 180 days following hospital discharge.

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.

What data supports the idea that Extended Release Buprenorphine for Opioid Use Disorder is an effective drug?

The available research shows that Extended Release Buprenorphine is an effective drug for treating opioid use disorder. One study found that it can be more effective than daily treatments like methadone or regular buprenorphine, as it reduces the risk of misuse and helps people stick to their treatment plan. Another study highlighted that people continued to benefit from the drug even 18 months after stopping it. This suggests that Extended Release Buprenorphine not only helps in the short term but also has lasting positive effects. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Extended Release Buprenorphine for treating opioid use disorder?

Research shows that extended-release buprenorphine, like Sublocade, is effective for treating opioid use disorder by reducing misuse and improving adherence compared to daily treatments. Studies also suggest it may offer continued benefits even after stopping the treatment. ^{1 2 3 4 5}

What safety data exists for extended-release buprenorphine for opioid use disorder?

Safety data for extended-release buprenorphine, including formulations like Sublocade, Brixadi, and Buvidal, indicate that these treatments are generally safer than sublingual buprenorphine due to reduced risks of overdose and misuse. The RECOVER study showed continued benefits 18 months post-treatment. Concerns exist about coercive use, but these formulations are appreciated for reducing daily intake burdens and aiding in treatment retention. Sublocade is approved for monthly use in the USA, with studies comparing the safety of different doses (100 mg vs. 300 mg) for opioid-injecting patients. ^{1 4 6 7 8}

Is extended-release buprenorphine safe for humans?

Extended-release buprenorphine, available under names like Sublocade and Brixadi, is generally considered safe for treating opioid use disorder. It has a lower risk of overdose compared to some other treatments and is appreciated for reducing the need for daily medication intake, although there are concerns about its long-acting nature potentially leading to coercive use. ^{1 4 6 7 8}

Is the drug Extended Release Buprenorphine a promising treatment for opioid use disorder?

Yes, Extended Release Buprenorphine is a promising treatment for opioid use disorder. It is effective and can be more convenient than daily treatments because it is given as a weekly or monthly injection. This can help reduce misuse and make it easier for people to stick to their treatment plan. ^{1 2 3 4 9}

How is extended-release buprenorphine different from other drugs for opioid use disorder?

Extended-release buprenorphine is unique because it is given as a weekly or monthly injection under the skin, which helps prevent misuse and ensures consistent treatment, unlike daily oral medications that can be missed or misused. ^{1 2 3 4 9}

Research Team

Gavin Bart, MD,PhD

Principal Investigator

Hennepin Heatlhcare

Eligibility Criteria

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

Able to speak English sufficiently to understand the study procedures and provide written informed consent to participate in the study

I am 18 years old or older.

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

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

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

Continued Posttrial Benefits of Buprenorphine Extended Release: RECOVER Study Findings. [2023]

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

Effect of Buprenorphine Weekly Depot (CAM2038) and Hydromorphone Blockade in Individuals With Opioid Use Disorder: A Randomized Clinical Trial. [2020]

3. England 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. [2023]

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

Subcutaneous Extended-Release Buprenorphine Use in Pregnancy. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

[New slow-release buprenorphine formulations for optimization of opioid substitution]. [2020]

6. France pubmed.ncbi.nlm.nih.gov

[Prolonged-release buprenorphine formulations: Perspectives for clinical practice]. [2022]

7. France pubmed.ncbi.nlm.nih.gov

Prolonged-release buprenorphine formulations: Perspectives for clinical practice. [2021]

8. England 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. [2023]

9. United States 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. [2022]