Long-acting Naltrexone for Opioid Addiction

Overseen By Michael S Gordon, DPA

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Friends Research Institute, Inc.

Must be taking: XR-NTX

Must not be taking: Methadone, Buprenorphine

Disqualifiers: Liver issues, Heart disease, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 13

Duration: 7 months

240 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a long-acting form of naltrexone (XR-NTX), a medication for opioid addiction. Researchers aim to determine if administering this medication at home, instead of at a treatment center, improves adherence to treatment plans after release from prison. The trial includes two groups: one receives the medication at home, the other at a treatment center. Ideal candidates are inmates who have remained opioid-free in prison and plan to reside in Baltimore post-release. Participants must not have serious untreated health issues or intend to use other opioid treatments like methadone. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment approach.

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

The trial does not specify if you need to stop taking your current medications, but it does allow for adequately treated medical and psychiatric conditions with appropriate medications. It seems you may continue certain medications if they are well-managed.

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

Research shows that long-acting naltrexone, also known as XR-NTX or Vivitrol, is generally safe. The FDA has approved it for treating opioid use disorder (OUD) and alcohol use disorder (AUD), confirming its safety through testing.

Past studies reported mild side effects, such as nausea or headaches, but these were not serious. The treatment involves a monthly injection, providing simplicity and consistency. Since it is already used for OUD and AUD, extensive safety information is available, which can reassure those considering participation in a trial with this medication. ^{1 2 3 4 5}

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

Researchers are excited about long-acting naltrexone, specifically XR-NTX, because it offers a unique approach to treating opioid addiction. Unlike traditional daily oral medications like methadone or buprenorphine, XR-NTX is administered as a monthly injection, which can improve adherence and reduce the risk of relapse. Additionally, XR-NTX blocks opioid receptors in the brain, preventing the euphoric effects of opioids, thus helping individuals maintain their recovery. This treatment is especially promising because it can be administered either at a participant's residence via mobile medical treatment or at a community opioid treatment program, offering flexibility in how care is delivered post-release from prison.

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

Research has shown that long-acting naltrexone (XR-NTX) can help prevent a return to opioid use. One study found that individuals receiving monthly XR-NTX injections were less likely to use opioids again. Another study suggested that starting XR-NTX treatment quickly could make it a more practical option for treating opioid addiction. In this trial, participants will receive XR-NTX either at their residence or at a community opioid treatment program. Additionally, naltrexone ranked as the fourth most effective medication for keeping patients in treatment compared to other drugs for opioid-related issues. These findings support XR-NTX as a promising option for those struggling with opioid addiction. ^{1 3 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 adults in prison due to be released within 30 days, living opioid-free with a history of opioid disorder. They must plan to live in Baltimore City or County and agree to XR-NTX treatment without seeking methadone or buprenorphine post-release. Excluded are those with severe liver issues, untreated serious mental health conditions, chronic pain on opioids, pregnant or breastfeeding women, high suicide risk individuals, and those with certain medical conditions.

Inclusion Criteria

Inmates not meeting the opioid-dependence criterion will be eligible if they were treated in an opioid agonist treatment program during the year before incarceration

Planning to live in Baltimore City or County

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

Exclusion Criteria

Suicidal ideation within the past 6-months

I do not have any untreated serious illnesses like heart disease or unstable diabetes.

Liver function test levels greater than three times normal

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

One injection of XR-NTX in prison, followed by six monthly injections post-release in the community

7 months

7 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 months

5 visits (in-person)

Long-term follow-up

Participants are evaluated for re-incarceration, criminal activity, and HIV risk behaviors

12 months

What Are the Treatments Tested in This Trial?

Interventions

• XR-NTX

Trial Overview The study tests if giving the drug XR-NTX at the patient's home improves adherence compared to receiving it at an opioid treatment program after release from prison. Participants will receive one injection before release and six monthly injections afterwards; they're randomly assigned to get these either at their residence or a treatment facility.

How Is the Trial Designed?

Group I: Vivitrol at place of residence Experimental Treatment 2 Interventions

One injection of long-acting naltrexone (XR-NTX) in prison, followed by 6 monthly injections post-release at the participants's place of residence utilizing mobile medical treatment

Group II: Vivitrol at opioid treatment program Active Control 2 Interventions

One injection of long-acting naltrexone (XR-NTX) in prison, followed by 6 monthly injections post-release at a community opioid treatment program.

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

Approved in United States as Vivitrol for:

• Opioid use disorder
• Alcohol use disorder

Approved in European Union as Naltrexone for:

• Opioid dependence
• Alcohol dependence

Approved in United States as ReVia for:

• Alcohol dependence

Approved in United States as Depade for:

• Alcohol dependence

Who Is Running the Clinical Trial?

Friends Research Institute, Inc.

Lead Sponsor

Trials

60

Recruited

22,500+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

Extended-release naltrexone (XR-NTX) is being tested as a monthly injectable treatment for opioid use disorders, specifically targeting individuals involved with the criminal justice system, in a 24-week open-label randomized controlled trial.

The study aims to determine if XR-NTX can effectively reduce opioid relapse rates compared to standard treatment options, with assessments occurring every two weeks and follow-ups at 12 and 18 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended-release naltrexone to prevent relapse among opioid dependent, criminal justice system involved adults: rationale and design of a randomized controlled effectiveness trial. Lee, JD., Friedmann, PD., Boney, TY., et al.[2018]

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]

A 24-week phase III trial with 250 opioid-dependent patients showed that the once-monthly extended-release formulation of naltrexone (XR-NTX) significantly increased the weeks of confirmed opioid abstinence compared to placebo, indicating its efficacy in preventing relapse after detoxification.

XR-NTX was generally well tolerated, though some patients experienced side effects like hepatic enzyme abnormalities and injection-site pain, suggesting it is a viable treatment option with manageable safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended-release intramuscular naltrexone (VIVITROL®): a review of its use in the prevention of relapse to opioid dependence in detoxified patients. Syed, YY., Keating, GM.[2021]

In an open-label study of 20 individuals with opioid addiction, a safe and effective outpatient transition to extended release injectable naltrexone (XR-NTX) was achieved using a combination of very low dose naltrexone and decreasing doses of buprenorphine over a 7-day period.

The results showed significant reductions in withdrawal symptoms, cravings, and drug use during the induction phase and after XR-NTX administration, with no serious adverse events reported, indicating a promising approach for outpatient treatment of opioid addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended release naltrexone injection is performed in the majority of opioid dependent patients receiving outpatient induction: a very low dose naltrexone and buprenorphine open label trial. Mannelli, P., Wu, LT., Peindl, KS., et al.[2021]

Extended-release naltrexone (XR-NTX) is being studied as a potentially more effective treatment for alcohol dependence compared to daily oral naltrexone (O-NTX), particularly due to its once-a-month injection format which may improve adherence and retention in treatment.

The study involves 237 participants over 24 weeks and aims to evaluate the effectiveness of XR-NTX in achieving abstinence or moderate drinking, while also assessing its cost-effectiveness compared to O-NTX in a primary care setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended-release vs. oral naltrexone for alcohol dependence treatment in primary care (XON). Malone, M., McDonald, R., Vittitow, A., et al.[2020]

Extended-release naltrexone (XR-NTX) has been shown to significantly increase both initial and 6-month abstinence in alcohol-dependent adults, particularly those who have achieved at least 4 days of initial abstinence.

In opioid dependence, XR-NTX effectively maintains abstinence, reduces cravings, and prevents relapse after detoxification, demonstrating its potential as a valuable treatment option in both primary care and public health systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intramuscular extended-release naltrexone: current evidence. Gastfriend, DR.[2022]

In a 1-year open-label extension study involving 114 patients, injectable extended-release naltrexone (XR-NTX) demonstrated long-term efficacy, with 50.9% of participants remaining abstinent from opioids throughout the study.

The treatment was generally safe, with only 21.1% of patients reporting adverse events and no severe adverse events noted, although 16.7% experienced elevated liver function tests.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Injectable extended-release naltrexone for opioid dependence: an open label study of long-term safety and efficacy]. Krupitsky, EM., Nunes, EV., Ling, W., et al.[2016]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5993595/

Extended-release injectable naltrexone for opioid use ... Pooled estimates showed that XR-NTX induction success was lower in studies that included individuals that required opioid detoxification (62.6% [95% CI: 54.5% – ...

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2818410

Rapid Initiation of Injection Naltrexone for Opioid Use ... The results of this trial suggest that rapid initiation could make XR-naltrexone a more viable treatment for patients with OUD.

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1505409

Extended-Release Naltrexone to Prevent Opioid Relapse ... This open-label, randomized, controlled effectiveness trial compared six monthly injections of extended-release naltrexone (Vivitrol, Alkermes) ...

4. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2022.1003257/full

The effects of naltrexone on retention in treatment and ... Overall, naltrexone was the fourth most effective medication among medications for opioid-related disorders than controls in terms of treatment retention after ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03647774

Long Acting Naltrexone for Opioid Addiction: Focus on ... The study will assess recovery outcomes and compare these with the clinical effectiveness of XR-NTX (use of illicit substances and safety). Further, the study ...

6. samhsa.gov samhsa.gov/substance-use/treatment/options/naltrexone

What is Naltrexone? Side Effects, Uses, Dose & Risk Naltrexone is a medication approved by the Food and Drug Administration (FDA) to treat both opioid use disorder (OUD) and alcohol use disorder (AUD).

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3411517/

Long-Acting Injectable Naltrexone for the Management of ... Dosing occurs once monthly and existing data with long-acting naltrexone supports efficacy of treatment for opioid dependence; however published data is sparse.

8. vivitrol.com vivitrol.com/content/pdfs/prescribing-information.pdf

Prescribing Information VIVITROL contains naltrexone, an opioid antagonist, and is indicated for the treatment of alcohol dependence in patients who are able to abstain from alcohol in ...