Buprenorphine/Naloxone for Opioid Use Disorder

Overseen By Frank J Vocci, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Friends Research Institute, Inc.

Must not be taking: Buprenorphine, Benzodiazepines, Methadone

Disqualifiers: Serious mental illness, Alcohol withdrawal, 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

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

Compensation: Varies

Number of Visits: 1

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This study proposes to compare a low-dose versus a high-dose buprenorphine induction scheme in 40 fentanyl using people with Opioid Use Disorder (OUD). Study participants will be randomized to either the low-dose (n=20) or high dose (n=20) group and dispensed medication daily for one week.

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 your urine test is positive for buprenorphine, benzodiazepines, or methadone.

What data supports the effectiveness of the drug Buprenorphine/Naloxone for opioid use disorder?

Buprenorphine/naloxone (Suboxone) is shown to be an effective treatment for opioid use disorder, especially when used as part of a comprehensive treatment program, as it helps improve outcomes for individuals seeking treatment. It is also noted to have a low potential for abuse when combined with naloxone, making it a safer option for managing opioid dependence. ^{1 2 3 4 5}

Is Buprenorphine/Naloxone safe for humans?

Buprenorphine/Naloxone is generally considered safe for treating opioid dependence, with a high safety profile and good tolerance. It is designed to reduce misuse and has been used safely in various studies, although there are some concerns about liver safety in patients with HIV. ^{2 4 6 7 8}

How is the drug buprenorphine/naloxone unique for treating opioid use disorder?

Buprenorphine/naloxone (Suboxone) is unique because it combines buprenorphine, which helps reduce cravings and withdrawal symptoms, with naloxone, which discourages misuse by causing withdrawal symptoms if injected. This combination allows it to be safely prescribed in a doctor's office, increasing access to treatment. ^{1 2 3 4 9}

Eligibility Criteria

This trial is for adults over 18 with Opioid Use Disorder who have used fentanyl, as confirmed by a urine test. Participants must be able to visit the clinic daily for one week.

Inclusion Criteria

My urine test was positive for fentanyl.

I can visit the clinic daily for the first week of treatment.

I am an adult diagnosed with opioid use disorder.

Exclusion Criteria

Urine positive for buprenorphine, benzodiazepines, or methadone

No exclusionary medical history or mental health issues as determined by the admitting provider; e.g., patients with untreated or unstable serious mental illness, including psychotic disorders

Enrolled in a methadone treatment program in the past 14 days

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Induction

Participants are randomized to either low-dose or high-dose buprenorphine induction scheme and receive daily medication for one week

1 week

Daily visits (in-person)

Treatment Adjustment

Dosing adjustments can be made according to the MATClinics usual schedule of clinic visits

3 months

Visits as needed based on opioid use

Follow-up

Participants are monitored for safety and effectiveness after induction, with follow-up visits at one and three months

3 months

Follow-up visits at 1 and 3 months

Treatment Details

Interventions

• Buprenorphine

Trial Overview The study is testing two different dosing strategies of buprenorphine/naloxone in treating OUD: a low-dose and a high-dose plan. Forty participants will be randomly assigned to either group and receive medication daily for one week.

Participant Groups

Group I: high dose Experimental Treatment 1 Intervention

High dose: Participants randomized to the high dose group will receive on day 1 in the clinic an initial dose of 2 mg of buprenorphine/naloxone, followed by a 6 mg dose an hour later, followed by an 8 mg dose an hour later, followed by an 8 mg dose an hour later. On day 2 they will receive a 12 mg dose in the clinic and a 12 mg dose as take-home medication. On days 3 through 7 they will report to the clinic and receive their 12 mg morning dose and a 12 mg dose as a take-home for evening dosing. Thereafter, dosing adjustments can be made in the first three months of the trial.

Group II: low dose Active Control 1 Intervention

Low dose: Participants randomized to the low dose group will receive 0.5 mg of buprenorphine/naloxone on day 1, 0.5 mg bid on day 2, 1.0 mg bid on day 3, 2.0 mg bid on day 4, 4.0 mg bid on day 5, 4.0 mg tid on day 6, and 8 mg bid on day 7. Thereafter, dosing adjustments can be made in the first three months of the trial.

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?

Friends Research Institute, Inc.

Lead Sponsor

Trials

60

Recruited

22,500+

MATClinics

Collaborator

Trials

1

Recruited

40+

Findings from Research

The study will involve 280 adults with opioid use disorder and aims to improve adherence to buprenorphine-naloxone treatment through two psychological interventions: contingency management (CM) and brief motivational interviewing plus substance-free activities and mindfulness (BSM).

The primary goal is to assess which intervention is more effective in promoting medication adherence, measured by attendance at physician appointments and the presence of buprenorphine in urine toxicology, with follow-up occurring 8 months after randomization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of a sequential multiple assignment randomized trial to test contingency management and an integrated behavioral economic and mindfulness intervention for buprenorphine-naloxone medication adherence for opioid use disorder. Peter, SC., Murphy, JG., Witkiewitz, K., et al.[2023]

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 32 veterans over three years, those receiving buprenorphine/naloxone in a group setting had a significantly higher retention rate in treatment after one year (69%) compared to those treated individually (27%).

The study also found that 94% of urine samples from participants were negative for opioids, indicating effective management of opioid use disorder with buprenorphine/naloxone in a group format.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Group medication management for buprenorphine/naloxone in opioid-dependent veterans. Berger, R., Pulido, C., Lacro, J., et al.[2014]

Buprenorphine is a safe and effective treatment for opioid dependence, particularly when combined with naloxone, which reduces its potential for abuse.

New regulations enable certified physicians to prescribe buprenorphine in their offices, significantly improving patient access to this important treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine maintenance: a new treatment for opioid dependence. Collins, GB., McAllister, MS.[2019]

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]

A 12-month study involving 384 opioid-dependent patients in Germany showed that buprenorphine-naloxone is highly effective and safe, with low rates of serious adverse events (1.2%) and no reported deaths.

The treatment led to significant improvements in mental health and quality of life, with a 57.1% retention rate, and 96.7% of patients who remained in treatment continued with buprenorphine-naloxone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, effectiveness and tolerance of buprenorphine-naloxone in the treatment of opioid dependence: results from a nationwide non-interventional study in routine care. Apelt, SM., Scherbaum, N., Gölz, J., et al.[2015]

In a study of 303 opioid-dependent HIV-infected patients, buprenorphine/naloxone treatment did not result in significant changes in liver enzymes (AST and ALT), indicating no measurable hepatic toxicity over time.

The study found no pharmacodynamic interactions between buprenorphine/naloxone and the antiretroviral drug atazanavir, suggesting that buprenorphine/naloxone is safe to use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatic safety and lack of antiretroviral interactions with buprenorphine/naloxone in HIV-infected opioid-dependent patients. Vergara-Rodriguez, P., Tozzi, MJ., Botsko, M., et al.[2020]

Buprenorphine is an opioid medication used for treating opioid dependence and managing moderate to severe pain, and it can be prescribed to pregnant women as part of their treatment for opioid addiction.

The chapter details a method for quantifying buprenorphine and its metabolite norbuprenorphine in meconium using liquid chromatography tandem mass spectrometry (LC-MS/MS), which is important for monitoring drug exposure in newborns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitation of Total Buprenorphine and Norbuprenorphine in Meconium by LC-MS/MS. Marin, SJ., McMillin, GA.[2016]

References

1. England pubmed.ncbi.nlm.nih.gov

Use of a sequential multiple assignment randomized trial to test contingency management and an integrated behavioral economic and mindfulness intervention for buprenorphine-naloxone medication adherence for opioid use disorder. [2023]

2. Ireland pubmed.ncbi.nlm.nih.gov

Abuse liability of buprenorphine-naloxone tablets in untreated IV drug users. [2015]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Group medication management for buprenorphine/naloxone in opioid-dependent veterans. [2014]

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

Buprenorphine maintenance: a new treatment for opioid dependence. [2019]

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

Emergency department visits and hospitalizations for buprenorphine ingestion by children--United States, 2010-2011. [2021]

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

Preference for buprenorphine/naloxone and buprenorphine among patients receiving buprenorphine maintenance therapy in France: a prospective, multicenter study. [2015]

7. Germany pubmed.ncbi.nlm.nih.gov

Safety, effectiveness and tolerance of buprenorphine-naloxone in the treatment of opioid dependence: results from a nationwide non-interventional study in routine care. [2015]

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

Hepatic safety and lack of antiretroviral interactions with buprenorphine/naloxone in HIV-infected opioid-dependent patients. [2020]

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

Quantitation of Total Buprenorphine and Norbuprenorphine in Meconium by LC-MS/MS. [2016]