Injectable Buprenorphine vs Naltrexone for Opioid Use Disorder

Overseen By Urooj Iqbal

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Pennsylvania

Must be taking: Opioid agonists, antagonists

Must not be taking: Antidepressants, antipsychotics

Disqualifiers: Psychotic disorders, Polysubstance use, 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: 3

Duration: 3 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments to assess their effects on the brain in individuals with opioid use disorder (OUD). Participants will receive monthly injections of either buprenorphine, an opioid addiction treatment, or naltrexone, a medication that blocks opioid effects. Both medications help curb opioid cravings. Researchers will use brain scans to track changes during tasks that test thinking skills. The trial seeks participants who primarily use opioids and are interested in injectable treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you have a psychiatric disorder that requires medication, you may not be eligible to participate.

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

Research has shown that injectable buprenorphine is usually well-tolerated for treating opioid use disorder. In one study, only about 4.7% of patients discontinued use due to side effects, indicating that most manage it well. Another study found it safe for long-term use, even though some did not complete the entire treatment.

Injectable naltrexone, already approved for treating alcohol dependence, has demonstrated similar safety results in studies for opioid use disorder. Common side effects occur in about 2% of people, but these are usually not serious. Overall, both treatments have been tested for safety and are generally well-accepted by most individuals. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for opioid use disorder because they offer innovative delivery methods and mechanisms of action. Unlike oral medications, both buprenorphine and naltrexone in this trial are administered as monthly injections, potentially improving adherence and reducing the risk of misuse. Buprenorphine acts as a partial agonist, which means it activates opioid receptors but to a lesser degree, providing relief from withdrawal symptoms without the same high. Naltrexone, on the other hand, is an antagonist that blocks opioid receptors, preventing the euphoric effects of opioids and helping to curb cravings. These unique approaches could offer new hope for individuals seeking effective and manageable treatment options.

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

This trial will compare the effectiveness of injectable Buprenorphine and Naltrexone for treating opioid use disorder (OUD). Research has shown that buprenorphine is effective for OUD, with large studies finding it lowers the risk of overdose and death. Monthly buprenorphine injections, which participants in one arm of this trial will receive, have helped patients improve over time.

In another arm of this trial, participants will receive naltrexone. Studies suggest that naltrexone helps delay relapse, allowing patients to stay on track longer. It can also lessen opioid cravings and help people adhere to their treatment. Both treatments have been shown to aid recovery in people with OUD. ^{1 2 3 5 6}

Who Is on the Research Team?

James Loughead, Ph.D.

Principal Investigator

University of Pennsylvania, Psychiatry

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with opioid use disorder, confirmed by medical assessment and tests. Participants must speak English, have a stable address and phone access. It's not for those with psychotic disorders, active liver disease, conditions affecting treatment safety or MRI contraindications. Women of childbearing age must use effective contraception.

Inclusion Criteria

I am prescribed opioids as my main pain medication.

I am open to trying long-lasting injectable treatments.

Diagnosed with OUD by DSM5 Criteria, confirmed by history and physical examination including urine toxicology, medical records, and self-report

Exclusion Criteria

I have a psychiatric condition but only take medication for mild to moderate depression, anxiety, or ADHD without stimulants.

I am of childbearing age and do not use birth control.

My main substance use is not opioids.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive three once-a-month injections of either buprenorphine or naltrexone and complete weekly monitoring visits

3 months

3 visits (in-person) for injections, weekly monitoring visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Buprenorphine
• Naltrexone

Trial Overview The study compares monthly injections of two drugs: Buprenorphine (Brixadi®) and Naltrexone (Vivitrol®), to understand their effects on the brain in people with opioid addiction. Brain activity will be monitored through MRIs before and after treatments over three months.

How Is the Trial Designed?

Group I: Buprenorphine Experimental Treatment 1 Intervention

Study participants receive three once-a-month injections of buprenorphine and complete weekly monitoring visits.

Group II: Naltrexone Active Control 1 Intervention

Study participants receive three once-a-month injections of naltrexone and complete weekly monitoring visits.

Buprenorphine is already approved in United States, European Union for the following indications:

Approved in United States as Buprenorphine for:

• Moderate to severe opioid addiction (dependence)

Approved in European Union as Buprenorphine for:

• Opioid dependence

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Published Research Related to This Trial

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 302 participants with cocaine dependence and a history of opioid dependence, buprenorphine + naloxone (BUP) combined with extended-release injectable naltrexone (XR-NTX) showed a significant reduction in cocaine use for those receiving 16 mg/day of BUP compared to placebo, indicating its potential effectiveness in this population.

However, no significant differences were observed in the primary outcome for the 4 mg/day BUP group compared to placebo, suggesting that higher doses may be necessary for efficacy, while adherence, retention, and adverse events were similar across all groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine + naloxone plus naltrexone for the treatment of cocaine dependence: the Cocaine Use Reduction with Buprenorphine (CURB) study. Ling, W., Hillhouse, MP., Saxon, AJ., et al.[2018]

In a 24-week study involving 570 patients with opioid use disorder, those who were homeless had a significantly lower relapse rate when treated with extended-release naltrexone (51.6%) compared to buprenorphine-naloxone (70.4%).

Conversely, non-homeless patients had a higher relapse rate with extended-release naltrexone (70.9%) compared to buprenorphine-naloxone (53.1%), indicating that demographic factors like homelessness can influence the effectiveness of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sublingual Buprenorphine-Naloxone Compared With Injection Naltrexone for Opioid Use Disorder: Potential Utility of Patient Characteristics in Guiding Choice of Treatment. Nunes, EV., Scodes, JM., Pavlicova, M., et al.[2021]

In a study involving 12 intravenous heroin users, buprenorphine/naloxone was self-administered significantly less often than buprenorphine or heroin, indicating a lower potential for misuse.

Participants reported lower 'drug liking' and 'desire to take the drug again' for buprenorphine/naloxone compared to buprenorphine alone, suggesting that this combination may be a safer option for treating opioid dependence while reducing the risk of misuse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abuse liability of intravenous buprenorphine/naloxone and buprenorphine alone in buprenorphine-maintained intravenous heroin abusers. Comer, SD., Sullivan, MA., Vosburg, SK., et al.[2022]

A study involving 53 opioid-dependent patients showed that switching from buprenorphine to buprenorphine/naloxone was well-tolerated, with no significant issues reported during the transition.

Patients expressed a preference for buprenorphine/naloxone over buprenorphine, with 54% favoring the combination formulation due to its taste and ease of use, indicating it may be a more acceptable option for maintenance treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preference for buprenorphine/naloxone and buprenorphine among patients receiving buprenorphine maintenance therapy in France: a prospective, multicenter study. Daulouède, JP., Caer, Y., Galland, P., et al.[2015]

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]

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]

A survey of intravenous drug users in Helsinki revealed that 73% used buprenorphine as their primary drug, primarily for self-treating addiction or withdrawal symptoms.

The combination of buprenorphine and naloxone (Suboxone) was tried by 68% of respondents, but 80% reported negative experiences, suggesting that while it may help reduce buprenorphine abuse, its acceptance among users is low.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abuse liability of buprenorphine-naloxone tablets in untreated IV drug users. Alho, H., Sinclair, D., Vuori, E., et al.[2015]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6585403/

Buprenorphine Treatment for Opioid Use Disorder Large clinical trials have shown that buprenorphine, dosed in this fashion, is more effective than a non-opioid, clonidine-based medically supervised withdrawal ...

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. cdc.gov cdc.gov/mmwr/volumes/73/wr/mm7325a1.htm

Treatment for Opioid Use Disorder: Population Estimates Medications for opioid use disorder (OUD), particularly buprenorphine and methadone, substantially reduce overdose-related and overall mortality ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0376871625002510

Extended-release injectable buprenorphine for the ... First, we used descriptive statistics to summarize participants' baseline characteristics, as well as to summarize the primary efficacy and safety outcomes.

5. recoveryanswers.org recoveryanswers.org/research-post/injectable-buprenorphine-1-year-outcomes/

Injectable buprenorphine for opioid use disorder: Effects on ... The current study examined the effects of monthly buprenorphine injections on patient-centered outcomes after up to 12 months of treatment.

6. brixadihcp.com brixadihcp.com/safety/

Clinical Safety Profile Adverse reactions led to premature discontinuation in 10 (4.7%) patients in the group receiving BRIXADI compared to 5 (2.3%) patients in the sublingual ...