Low-Dose Buprenorphine for Opioid Use Disorder

Overseen By Benjamin T Hayes, MD, MS, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Montefiore Medical Center

Must not be taking: Methadone, Buprenorphine, Naltrexone

Disqualifiers: Alcohol use disorder, Benzodiazepine use disorder, Severe mental illness, 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: 5

Duration: 8 days

70 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

If you are currently taking FDA-approved medications for opioid use disorder, like methadone, buprenorphine, or naltrexone, you must stop at least 14 days before joining the study.

What data supports the effectiveness of the drug buprenorphine-naloxone for opioid use disorder?

Research shows that buprenorphine-naloxone is effective in treating opioid use disorder, especially when used as part of a comprehensive treatment program. It helps improve treatment outcomes, although adherence to the medication can be a challenge. ^{1 2 3 4 5}

Is low-dose buprenorphine generally safe for humans?

Buprenorphine, often combined with naloxone, is generally well tolerated and considered safe for treating opioid use disorder in adults and adolescents over 15 years old. While it has a potential for abuse similar to other opioids, its combination with naloxone helps reduce misuse, and adverse effects are usually mild and rare. ^{1 6 7 8 9}

How is the drug Buprenorphine-naloxone unique for treating opioid use disorder?

Buprenorphine-naloxone is unique because it combines buprenorphine, which helps reduce cravings and withdrawal symptoms, with naloxone, which deters misuse by causing withdrawal symptoms if injected. This combination aims to improve treatment adherence and reduce the risk of misuse compared to other treatments. ^{1 3 8 10 11}

What is the purpose of this trial?

The purpose of this study is to test whether low-dose buprenorphine initiation for treatment of opioid use disorder is safe and effective.

Research Team

Benjamin T Hayes, MD, MS, MPH

Principal Investigator

Montefiore Medical Center

Eligibility Criteria

Adults over 18 with opioid use disorder who are willing to follow study procedures and can take sublingual medication. They must not be pregnant, lactating, or have cognitive impairments that prevent consent. Participants should not be on other FDA-approved medications for opioid use disorder or have severe mental illness.

Inclusion Criteria

For participants of reproductive potential: agreement to use highly effective contraception during study participation

Provision of signed and dated informed consent form

Diagnosis of Opioid Use Disorder (based on Diagnostic and Statistical Manual- Version 5 criteria)

Exclusion Criteria

Pregnancy or lactation

Severe untreated mental illness, meaning psychosis or suicidality

Diagnosis of Alcohol Use Disorder, severe or Benzodiazepine Use Disorder, severe (based on Diagnostic and Statistical Manual- Version 5 criteria)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to either an 8-day low-dose buprenorphine initiation protocol or treatment as usual, with study visits at baseline, week 2, and week 4.

8 days

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments at 2-week and 6-week visits.

6 weeks

2 visits (in-person)

Treatment Details

Interventions

• Buprenorphine-naloxone

Trial Overview The trial is testing the safety and effectiveness of starting treatment for opioid addiction with a low dose of buprenorphine-naloxone. The goal is to see if this approach helps people manage their condition better than current methods.

Participant Groups

Group I: Low-dose initiation Experimental Treatment 1 Intervention

Participants randomized to low-dose buprenorphine initiation will start low-dose buprenorphine-naloxone (bup-nx) according to an at-home, 8-day protocol (below). Participants in the low-dose buprenorphine initiation arm will be allowed to continue taking the full opioid agonist that they were taking at the time of enrollment until they reach a therapeutic dose of buprenorphine-naloxone. Day 1: 0.5 mg once; Day 2: 0.5 mg every 12 hours; Day 3: 1 mg every 12 hours; Day 4: 2 mg every 12 hours; Day 5: 3mg every 12 hours; Day 6: 4 mg every 12 hours; Day 7: 6 mg every 12 hours; Day 8: 8 mg every 12 hours

Group II: Treatment as usual Active Control 1 Intervention

Participants randomized to treatment as usual will start buprenorphine-naloxone (bup-nx) following standard clinical guidelines for two-day, at-home initiation.

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

Approved in United States as Suboxone for:

• Opioid use disorder

Approved in European Union as Suboxone for:

• Opioid dependence

Approved in United States as Zubsolv for:

• Opioid use disorder

Approved in European Union as Zubsolv for:

• Opioid dependence

Who Is Running the Clinical Trial?

Montefiore Medical Center

Lead Sponsor

Trials

468

Recruited

599,000+

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]

The novel weekly subcutaneous buprenorphine depot formulation, CAM2038, was found to effectively block the euphoric effects of opioids and suppress withdrawal symptoms in individuals with moderate-to-severe opioid use disorder, based on a study involving 47 participants.

Both doses of CAM2038 (24 mg and 32 mg) were well-tolerated and demonstrated significant efficacy in preventing opioid effects, making it a promising alternative to daily oral formulations that carry risks of misuse and nonadherence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Buprenorphine Weekly Depot (CAM2038) and Hydromorphone Blockade in Individuals With Opioid Use Disorder: A Randomized Clinical Trial. Walsh, SL., Comer, SD., Lofwall, MR., et al.[2020]

In a clinical trial with 428 participants, weekly and monthly subcutaneous (SC) buprenorphine depot formulations were found to be noninferior to daily sublingual (SL) buprenorphine with naloxone in treating opioid use disorder, showing similar response rates and urine test results for opioid use.

The SC buprenorphine group demonstrated a statistically superior cumulative distribution function (CDF) for no illicit opioid use compared to the SL buprenorphine group, suggesting that depot formulations may offer additional benefits in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly and Monthly Subcutaneous Buprenorphine Depot Formulations vs Daily Sublingual Buprenorphine With Naloxone for Treatment of Opioid Use Disorder: A Randomized Clinical Trial. Lofwall, MR., Walsh, SL., Nunes, EV., et al.[2022]

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]

The new sublingual buprenorphine/naloxone tablet (Zubsolv®) has higher bioavailability and better taste, which may improve patient adherence and reduce the risk of misuse compared to the reference product (Suboxone®).

In large phase III trials lasting up to 28 days, Zubsolv® demonstrated high treatment retention rates and effectively reduced opioid cravings and withdrawal symptoms, making it a viable option for treating opioid dependence in adults and adolescents over 15 years old.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine/Naloxone (Zubsolv®): A Review in Opioid Dependence. Heo, YA., Scott, LJ.[2021]

Buprenorphine, approved for treating opiate dependence, has been found to have an abuse potential similar to that of traditional opioids like morphine, despite initial beliefs of its low abuse risk.

A study of 120 buprenorphine abusers revealed that the majority were middle-aged males with a significant history of early illicit drug use, highlighting a concerning trend of prescription medication abuse that requires increased awareness and vigilance among healthcare professionals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Socio-demographic profile and help-seeking behaviour of buprenorphine abusers in Singapore. Winslow, M., Ng, WL., Mythily, S., et al.[2020]

In a study of 50 African-American patients with opioid use disorders, only 48% adhered to buprenorphine-naloxone treatment, with non-adherence linked to higher rates of cocaine and alcohol use.

Participation in cognitive behavioral therapy (CBT) was significantly associated with better adherence to treatment, while patients with PTSD symptoms showed higher adherence compared to those without, suggesting that addressing co-occurring substance use and providing therapy may enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors associated with non-adherence to Buprenorphine-naloxone among opioid dependent African-Americans: A retrospective chart review. Kumari, S., Manalai, P., Leong, S., et al.[2022]

Increasing access to buprenorphine, a treatment for opioid use disorder, is crucial for reducing overdose deaths, but limited availability of buprenorphine monoproduct is a significant barrier.

The requirement to prescribe buprenorphine as a combination product with naloxone may lead to adverse effects that are more serious than previously thought, potentially harming the patient-provider relationship and increasing stigma, which can hinder access to care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Naloxone Component of Buprenorphine/Naloxone: Discouraging Misuse, but at What Cost? Gregg, J., Hartley, J., Lawrence, D., et al.[2023]

In a study of 566 patients receiving buprenorphine for opioid use disorder, those treated with doses greater than 16 mg per day showed significantly higher retention rates in care at both 30 days (95.4% vs 86.7%) and 90 days (82.7% vs 67.6%) compared to those receiving 16 mg.

The findings suggest that higher doses of buprenorphine (>16 mg) may be more effective in retaining patients in treatment, indicating that current dose caps may limit the effectiveness of treatment for opioid use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Higher buprenorphine dose associated with increased treatment retention at low threshold buprenorphine clinic: A retrospective cohort study. Selitsky, L., Nordeck, C., Truong, A., et al.[2023]

Buprenorphine is a safe and effective treatment for opioid use disorder (OUD) in emergency departments, acting as a partial mu-opioid receptor agonist with a long half-life and a ceiling effect that reduces the risk of overdose and withdrawal symptoms.

Implementing a buprenorphine program in the ED requires a comprehensive approach that includes medication-assisted treatment, counseling, and addressing the stigma associated with opioid replacement therapies to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Approach to buprenorphine use for opioid withdrawal treatment in the emergency setting. Cisewski, DH., Santos, C., Koyfman, A., et al.[2019]

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

Effect of Buprenorphine Weekly Depot (CAM2038) and Hydromorphone Blockade in Individuals With Opioid Use Disorder: A Randomized Clinical Trial. [2020]

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

Weekly and Monthly Subcutaneous Buprenorphine Depot Formulations vs Daily Sublingual Buprenorphine With Naloxone for Treatment of Opioid Use Disorder: A Randomized Clinical Trial. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

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

6. New Zealand pubmed.ncbi.nlm.nih.gov

Buprenorphine/Naloxone (Zubsolv®): A Review in Opioid Dependence. [2021]

7. Singapore pubmed.ncbi.nlm.nih.gov

Socio-demographic profile and help-seeking behaviour of buprenorphine abusers in Singapore. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Factors associated with non-adherence to Buprenorphine-naloxone among opioid dependent African-Americans: A retrospective chart review. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

The Naloxone Component of Buprenorphine/Naloxone: Discouraging Misuse, but at What Cost? [2023]

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

Higher buprenorphine dose associated with increased treatment retention at low threshold buprenorphine clinic: A retrospective cohort study. [2023]

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

Approach to buprenorphine use for opioid withdrawal treatment in the emergency setting. [2019]