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

240 Participants Needed

Trial Summary

What is the purpose of this trial?

The proposed study is a Type 1 hybrid effectiveness-implementation trial. Individuals with opioid use disorder in county jails throughout the state of Maryland will be randomly assigned within gender within jail to one of two groups: Arm 1. XR-B (n=120). XR-B in jail followed by 6 monthly injections post-release at a community treatment program. Arm 2. XR-NTX (n=120). One injection of XR-NTX in jail, followed by 6 monthly injections post-release at a community treatment program.

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 extended-release naltrexone or buprenorphine safe for treating opioid use disorder?

Research shows that both extended-release naltrexone (XR-NTX) and buprenorphine-naloxone (BUP-NX) are generally safe for treating opioid use disorder, with no significant differences in safety outcomes between the two treatments. ^{1 2 3 4 5}

Is extended-release naltrexone or buprenorphine safe for treating opioid use disorder?

Research shows that both extended-release naltrexone (XR-NTX) and buprenorphine-naloxone (BUP-NX) are generally safe for treating opioid use disorder, with no significant differences in safety outcomes between the two treatments. ^{1 2 3 4 5}

How does the drug XR-NTX differ from BUP-NX for opioid use disorder?

XR-NTX is a monthly injectable drug that blocks opioid effects, while BUP-NX is a daily sublingual drug that partially activates opioid receptors. XR-NTX requires detoxification before starting, making it harder to initiate compared to BUP-NX. ^{1 2 4 6 7}

How does the drug extended-release naltrexone compare to buprenorphine for opioid use disorder?

Extended-release naltrexone (XR-NTX) is unique because it is a monthly injection that blocks opioid effects, while buprenorphine-naloxone (BUP-NX) is a daily sublingual (under the tongue) medication that partially activates opioid receptors. XR-NTX is as effective as BUP-NX in preventing opioid relapse, but it requires complete detoxification before starting, which can be challenging for some patients. ^{1 2 4 6 7}

Research Team

Michael S Gordon, DPA

Principal Investigator

Friends Research Institute, Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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]

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]

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]

References

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

Patients' perspectives on initiating treatment with extended-release naltrexone (XR-NTX). [2022]

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

Cost-Effectiveness of Buprenorphine-Naloxone Versus Extended-Release Naltrexone to Prevent Opioid Relapse. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Risk of Relapse Among Opioid-Dependent Patients Treated With Extended-Release Naltrexone or Buprenorphine-Naloxone: A Randomized Clinical Trial. [2021]

4. United States 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. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Extended-release injectable naltrexone for opioid use disorder: a systematic review. [2019]

6. England 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. [2023]

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

Does XR injectable naltrexone prevent relapse as effectively as daily sublingual buprenorphine-naloxone? [2021]