Extended Release Naltrexone vs Buprenorphine for Opioid Use Disorder

Overseen By Thomas R Blue, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Friends Research Institute, Inc.

Must not be taking: Macrolides, Azoles, Anti-arrythmics, Antipsychotics

Disqualifiers: Liver issues, Heart 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: 6

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, extended-release buprenorphine (XR-B) and extended-release naltrexone (XR-NTX), to assist individuals with opioid use disorder. The goal is to determine the effectiveness of these treatments for those who have been in jail and are nearing release. Participants will receive injections either in jail or after release as part of a community treatment program. Ideal candidates for this trial have a history of opioid use disorder, are close to being released from jail, and plan to live in specific counties in Maryland. As a Phase 2 trial, this research measures the effectiveness of these treatments in an initial, smaller group, allowing participants to contribute to significant findings.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot participate if you are currently on medications that prolong the QTc interval or if you are enrolled in jail-based MOUD pharmacotherapy like methadone, buprenorphine, or naltrexone.

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 are on medications that affect heart rhythm or if you are currently in a jail-based opioid treatment program. It's best to discuss your specific medications with the trial team.

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

Research has shown that extended-release buprenorphine (XR-B) is generally safe and well-tolerated for people with opioid use disorder. Studies have found that doses over 16 mg are safe for patients. People using XR-B had fewer hospital and emergency room visits, suggesting it helps reduce health issues related to opioid use.

Research also indicates that extended-release naltrexone (XR-NTX) is safe and has been used successfully to prevent opioid relapse. While starting treatment might be challenging for some, many respond well once they begin.

Both treatments aim to help people with opioid use disorder and are considered safe based on current research. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments, XR-B (extended-release buprenorphine) and XR-NTX (extended-release naltrexone), because they offer unique benefits for opioid use disorder. XR-B is distinctive because it provides a long-acting formulation of buprenorphine, potentially reducing the need for daily dosing and improving compliance. XR-NTX offers an extended-release version of naltrexone that works by blocking opioid receptors, which can help prevent relapse without the need for the daily discipline of taking a pill. Both treatments aim to simplify the management of opioid use disorder, offering more convenience and potentially better adherence compared to current daily dosing regimens.

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

In this trial, participants will receive either extended-release buprenorphine (XR-B) or extended-release naltrexone (XR-NTX) to treat opioid use disorder. Research has shown that XR-B can significantly reduce drug use in individuals with opioid addiction, help them remain in treatment longer, and result in fewer re-arrests compared to other treatments. In contrast, XR-NTX has shown mixed results; it works well for some individuals but requires detoxification first, which can be challenging. However, XR-NTX can double the chances of staying in treatment compared to some other options. Both treatments offer benefits, but the right choice depends on individual needs and circumstances. ^{1 2 6 7 8}

Who Is on the Research Team?

Michael S Gordon, DPA

Principal Investigator

Friends Research Institute, Inc.

Are You a Good Fit for This Trial?

This trial is for adult male and female inmates in Maryland with moderate to severe opioid use disorder, or those treated for it within the last year. They must be due for release within 120 days, plan to live locally post-release, and pass a medical evaluation. Exclusions include severe liver issues, certain heart diseases or conditions that affect heart rhythm, untreated serious mental health disorders, pregnancy or breastfeeding women, extreme obesity (BMI > 40), and current enrollment in other medication-assisted treatments.

Inclusion Criteria

Planning to live in one of the 7 participating counties and/or surrounding counties

I am considered suitable for XR-B/XR-NTX treatment after a medical check.

I am an inmate due for release within the next 4 months.

Exclusion Criteria

I do not have any severe illnesses that could make participating dangerous.

Breastfeeding (for women)

I am prescribed opioids for my chronic pain.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either XR-B or XR-NTX in jail, followed by 6 monthly injections post-release at a community treatment program

6 months

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including pharmacotherapy adherence and various health and behavioral outcomes

12 months

What Are the Treatments Tested in This Trial?

Interventions

• XR-B
• XR-NTX

Trial Overview The study compares two extended-release medications given to individuals leaving jail: XR-B (buprenorphine) versus XR-NTX (naltrexone). Participants will receive one treatment while incarcerated followed by six monthly injections after release. The assignment of either XR-B or XR-NTX is random within gender groups.

How Is the Trial Designed?

Group I: XR-B Experimental Treatment 1 Intervention

Extended-release buprenorphine

Group II: XR-NTX Active Control 1 Intervention

Extended-release naltrexone

XR-B is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Buprenorphine for:

• Opioid use disorder
• Pain management

Approved in European Union as Buprenorphine for:

• Opioid dependence
• Chronic pain

Approved in Canada as Buprenorphine for:

• Opioid use disorder
• Severe chronic pain

Who Is Running the Clinical Trial?

Friends Research Institute, Inc.

Lead Sponsor

Trials

60

Recruited

22,500+

Published Research Related to This Trial

Extended-release naltrexone (XR-NTX) is viewed positively by patients for its once-monthly dosing and lack of physical dependence, but barriers such as ambivalence and unfamiliarity with antagonist treatment hinder initiation, especially in the context of opioid detoxification.

Once patients initiate XR-NTX, they report it as an effective treatment for opioid use disorder (OUD), with high satisfaction and sustained abstinence, indicating its potential as a viable long-term solution for managing OUD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patients' perspectives on initiating treatment with extended-release naltrexone (XR-NTX). Gauthier, P., Greco, P., Meyers-Ohki, S., et al.[2022]

Monthly extended-release injectable naltrexone (XR-NTX) is as effective as daily sublingual buprenorphine-naloxone (BUP-NX) in treating opioid use disorder, based on two good-quality randomized controlled trials.

Both treatments do not lead to an increase in serious adverse events or fatal overdoses, indicating that XR-NTX is a safe alternative for managing opioid use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does XR injectable naltrexone prevent relapse as effectively as daily sublingual buprenorphine-naloxone? Roe, M., Wilson, CG., Fusco, CW., et al.[2021]

In a study of 143 opioid-dependent patients, those treated with extended-release naltrexone (XR-NTX) had a significantly lower risk of relapse to heroin and other illicit opioids compared to those treated with buprenorphine-naloxone (BP-NLX), with hazard ratios indicating a much lower likelihood of relapse in the XR-NTX group.

The results suggest that XR-NTX not only reduces the risk of relapse in the short term but also maintains a stable low risk of relapse over a longer follow-up period, supporting its use as a first-line treatment for opioid addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of Relapse Among Opioid-Dependent Patients Treated With Extended-Release Naltrexone or Buprenorphine-Naloxone: A Randomized Clinical Trial. Opheim, A., Gaulen, Z., Solli, KK., et al.[2021]

In a study involving 570 adults with opioid use disorder, buprenorphine-naloxone was found to be more cost-effective than extended-release naltrexone, being preferred in 97% of cases at 24 weeks and 85% at 36 weeks based on quality-adjusted life-years (QALYs).

The analysis suggests that buprenorphine-naloxone is the better first-line treatment option, especially for patients needing detoxification before starting extended-release naltrexone, although the study had limitations such as a relatively short follow-up period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness of Buprenorphine-Naloxone Versus Extended-Release Naltrexone to Prevent Opioid Relapse. Murphy, SM., McCollister, KE., Leff, JA., et al.[2020]

In the X:BOT trial involving 474 participants with opioid use disorder, both extended-release naltrexone (XR-NTX) and buprenorphine-naloxone (BUP-NX) effectively reduced drinking behaviors, but neither treatment was superior in this regard.

Only a small portion of the participants had alcohol use disorder (AUD), which limited the ability to detect significant differences in drinking outcomes between the two treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is extended release naltrexone superior to buprenorphine-naloxone to reduce drinking among outpatients receiving treatment for opioid use disorder? A secondary analysis of the CTN X:BOT trial. Roache, JD., Pavlicova, M., Campbell, A., et al.[2023]

In a study of 79 US military veterans with opioid use disorder, both extended-release injectable naltrexone (XR-NTX) and buprenorphine/naloxone (BUP-NX) showed similar treatment retention and outcomes over a 90-day period, indicating that both medications are effective options.

While the BUP-NX group had a higher prevalence of pain diagnoses, there were no significant differences in substance use outcomes, suggesting that both treatments can be safely used in veterans with various medical and psychiatric comorbidities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine Naloxone and Extended Release Injectable Naltrexone for the Treatment of Opioid Use Disorder Among a Veteran Patient Sample: A Retrospective Chart Review. Shirk, SD., Ameral, V., Kraus, SW., et al.[2021]

Induction success for extended-release naltrexone (XR-NTX) is significantly lower in individuals requiring opioid detoxification (62.6%) compared to those already detoxified (85.0%), indicating that detoxification status is crucial for treatment initiation.

Adherence to XR-NTX is relatively low, with only 44.2% of individuals completing all scheduled injections, and adherence rates are notably higher in controlled research settings compared to routine care, which limits the overall effectiveness of XR-NTX in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended-release injectable naltrexone for opioid use disorder: a systematic review. Jarvis, BP., Holtyn, AF., Subramaniam, S., et al.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38940929/

Feasibility and effectiveness of extended-release ... Compared to other MOUD, XR-BUP significantly reduced drug use, resulted in similar or higher treatment retention rates, fewer re-incarcerations, ...

2. 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 ...

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. 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 ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/add.70106

Extended‐release buprenorphine treatment for opioid use ... Three outcome measures from the trial's dataset were used descriptively: (1) fortnightly clinic visit administered TimeLine Follow-Back ...

6. nih.gov nih.gov/news-events/news-releases/higher-doses-buprenorphine-may-improve-treatment-outcomes-people-opioid-use-disorder

Higher doses of buprenorphine may improve treatment ... Studies have shown that more than 16 mg of buprenorphine is safe and well tolerated in people with opioid use disorder in emergency department ...

7. 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 ...

8. recoveryanswers.org recoveryanswers.org/research-post/real-world-effects-extended-release-buprenorphine/

Real-world effects of extended-release buprenorphine For every four weeks that a patient remained on extended-release buprenorphine, the likelihood of substance use decreased by 8% to 20% across various substances ...