Extended-release vs Sublingual Buprenorphine for Opioid Use Disorder

(RXR Trial)

Recruiting at 7 trial locations

Overseen By Cynthia Boubion, BA

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Yih-Ing Hser

Must be taking: Buprenorphine

Must not be taking: Naltrexone, Methadone

Disqualifiers: Psychiatric disorder, Suicidal ideation, Alcohol use, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 14

Duration: 12 weeks

144 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 (OUD), to determine which is more effective in rural areas. One group receives an extended-release injection every four weeks, while the other takes a daily under-the-tongue tablet. The researchers aim to compare these treatments in terms of effectiveness, convenience, and patient satisfaction. Individuals with moderate to severe OUD who are already using or interested in buprenorphine treatment and willing to try either form might be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to significant research that could lead to new treatment options.

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

Research shows that both extended-release buprenorphine and sublingual buprenorphine are generally safe for treating opioid use disorder. Studies have found that extended-release buprenorphine (XR-BUP) is usually well-tolerated, with a safety profile similar to sublingual buprenorphine-naloxone, a pill that dissolves under the tongue. Most side effects are mild, such as headaches or nausea.

Sublingual buprenorphine is already a common and effective treatment for opioid use disorder and has been used safely by many people. When combined with naloxone, sometimes called SL-BUP, it helps reduce misuse, meaning using the drug in a way it wasn't prescribed.

Both treatments have been extensively studied and have shown a good track record for safety. Evidence supports that they are generally well-tolerated by patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments for opioid use disorder being tested because they offer new ways to manage this challenging condition. Unlike traditional sublingual buprenorphine, which requires daily dosing, extended-release buprenorphine (XR-BUP) is administered via injection and lasts for weeks, potentially improving adherence by reducing the burden of daily medication. This could mean fewer missed doses and more consistent management of cravings and withdrawal symptoms. Additionally, having an injectable option might provide more flexibility and convenience for patients who struggle with the routine of daily medication. These features could make a big difference in the lives of those dealing with opioid dependency.

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

This trial will compare extended-release buprenorphine (XR-BUP) with sublingual buprenorphine (SL-BUP) for treating opioid use disorder (OUD). Research has shown that XR-BUP effectively treats OUD. In one study, patients using XR-BUP reported greater satisfaction with their treatment over time compared to those using SL-BUP. Another study found XR-BUP effective for patients at high risk of overdose. SL-BUP has also proven effective for OUD, with patients adhering to their treatment and experiencing a low chance of relapse. Both treatments help by reducing cravings and withdrawal symptoms, making it easier for patients to manage OUD. ^{1 4 5 6 7}

Who Is on the Research Team?

Yih-Ing Hser, PhD

Principal Investigator

University of California, Los Angeles

Larissa Mooney, MD

Principal Investigator

University of California, Los Angeles

Are You a Good Fit for This Trial?

This trial is for adults over 18 with moderate to severe opioid use disorder (OUD) who live in rural areas. They must speak English, agree to birth control if applicable, and be willing to take either sublingual or injectable buprenorphine as treatment. People can't join if they've recently used methadone, have certain medical or psychiatric conditions, are pregnant/breastfeeding, or have legal issues that could interfere.

Inclusion Criteria

Be willing and able to provide written informed consent to participate in the study

I have a moderate to severe opioid use disorder or am on buprenorphine.

I am open to being assigned to either SL-BUP or XR-BUP treatment.

Exclusion Criteria

Have a current pattern of alcohol, benzodiazepine, or other sedative hypnotic use, as determined by the study Medical Clinician, that would require a different level of care and preclude safe participation in the study

Have been in methadone maintenance treatment within 28 days of consent

Be currently incarcerated or have pending legal action that could preclude participation in study activities

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction/Stabilization

Initial period of induction and stabilization with study medication

2 weeks

Weekly visits for dosage titration

Treatment

Participants receive study medication for opioid use disorder

12 weeks

Injections at Day 14, Week 6, and Week 10 for XR-BUP; similar schedule for SL-BUP

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Extended-release Buprenorphine
• Sublingual Buprenorphine

Trial Overview The study compares two forms of buprenorphine: a monthly injectable extended-release version (XR-BUP) and a daily sublingual tablet (SL-BUP). Participants will be randomly assigned to one of these treatments for 14 weeks and monitored through assessments and interviews to determine which is more effective in rural settings.

How Is the Trial Designed?

Group I: Injectable extended-release buprenorphine (XR-BUP) Experimental Treatment 1 Intervention

Participants will be randomly assigned to XR-BUP, with approximately 96 in the XR-BUP condition. The XR-BUP condition will use Brixadi/CAM2038 injectable, extended-release buprenorphine (Braeburn Pharmaceuticals, Inc.). After titrating to a stable dosage in approximately two weeks using weekly injection dosages as clinically indicated to relieve cravings and withdrawal symptoms, the target monthly dosage (128mg) of XR-BUP will be administered by injection at approximately Day 14 and approximately four weeks later in Week 6, with a third injection in Week 10. Dosage adjustments will be made as indicated for tolerability.

Group II: Sublingual buprenorphine-naloxone (SL-BUP) Active Control 1 Intervention

Participants will be randomly assigned to SL-BUP with approximately 48 in the SL-BUP condition. The SL-BUP condition will use sublingual buprenorphine-naloxone, with a target maintenance daily dose range of 16-24mg as recommended for clinical practice. Titration to maintenance dosage will be attempted within the first two weeks of the SL-BUP condition. During the initial stabilization weeks, SL-BUP will be flexibly dosed as clinically indicated to relieve cravings and withdrawal symptoms, after which dosage adjustments will be based on clinical decisions by the site clinicians. The maintenance dosage of SL-BUP will be dispensed on a schedule similar to the XR-BUP injections (i.e., at approximately Day 14, Week 6, and Week 10).

Who Is Running the Clinical Trial?

Yih-Ing Hser

Lead Sponsor

Trials

1

Recruited

140+

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

University of California, Los Angeles

Collaborator

Trials

1,594

Recruited

10,430,000+

University of Illinois at Chicago

Collaborator

Trials

653

Recruited

1,574,000+

RAND

Collaborator

Trials

145

Recruited

617,000+

Cornell University

Collaborator

Trials

179

Recruited

14,090,000+

West Virginia University

Collaborator

Trials

192

Recruited

64,700+

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

University of Washington

Collaborator

Trials

1,858

Recruited

2,023,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06023459

Extended-release Buprenorphine Compared to Sublingual ... The measure for the main comparative effectiveness outcome is number of urine drug screen (UDS) results negative for opioids at scheduled assessments during ...

2. 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 ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40459195/

Transition to Extended-release Buprenorphine Injectable ... Of patients, 4% experienced withdrawal symptoms requiring additional opioid support. All Bup-LA-B studies reported transitions within 24 hours.

4. link.springer.com link.springer.com/article/10.1007/s40267-024-01055-y

Buprenorphine extended-release injection (Brixadi®) in the ... In the DEBUT trial, patients who received subcutaneous buprenorphine ER reported higher and more sustained treatment satisfaction than those who ...

5. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2809294

Extended-Release Buprenorphine for Persons With Opioid ... Treatment with extended-release buprenorphine yielded lower effectiveness by 0.03 quality-adjusted life-years per person at higher cost.

6. 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 ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11954470/

Initiation and Dosing of Extended-Release Buprenorphine Individuals with Opioid Use Disorder (OUD) who use fentanyl are at high risk of mortality due to opioid-related overdose.