Buprenorphine Formulations for Opioid Use Disorder

Overseen By John Mariani, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Rachel R. Luba

Must not be taking: Methadone, Sedative-hypnotics, Alcohol, others

Disqualifiers: Other substance use disorder, unmanaged psychiatric, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 13

Duration: 12 weeks

60 Participants Needed

Trial Summary

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've used medications or herbal products that affect liver enzymes (CYP3A4) in the past 30 days.

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

Research shows that Buprenorphine is an effective and widely used medication for treating opioid use disorder, helping to reduce harms associated with the condition. It is especially beneficial when patients remain in treatment, and new formulations may help improve adherence and reduce misuse. ^{1 2 3 4 5}

Is buprenorphine safe for humans?

Buprenorphine is generally considered safe for treating opioid dependence, with a lower risk of overdose compared to other treatments. However, there are concerns about misuse, especially when tablets are injected, which can lead to serious health issues. Studies show that formulations like Suboxone, which combine buprenorphine with naloxone, are designed to reduce misuse while maintaining safety. ^{6 7 8 9 10}

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

Buprenorphine is unique because it is a partial agonist at mu receptors, which helps reduce cravings and withdrawal symptoms without producing the same high as full agonists like heroin. It is available in various formulations, including sublingual tablets and films, and some versions are combined with naloxone to prevent misuse. ^{5 9 11 12 13}

What is the purpose of this trial?

The goal of this clinical trial is to compare buprenorphine formulations (sublingual buprenorphine versus long-acting injectable buprenorphine) for treating opioid use disorder among individuals who use fentanyl and/or other high potency synthetic opioids. Individuals aged 18-65 will be eligible for enrollment. The main questions it aims to answer are: Are there differences in frequency of drug use after individuals start treatment with sublingual buprenorphine compared to injectable buprenorphine? Are there differences in rates of sustained relapse after individuals start treatment with sublingual buprenorphine compared to injectable buprenorphine? Investigators also seek to understand and explore: How factors like body fat, body weight, and quantity of fentanyl use before treatment influence treatment outcomes. How blood levels of buprenorphine and its metabolite norbuprenorphine early on in treatment may influence treatment outcomes. How factors like craving and opioid withdrawal symptoms influence treatment outcomes. Participants will: Complete a brief overnight hospital stay in an inpatient research unit. This hospital stay will enable participants to start treatment with either sublingual buprenorphine or injectable buprenorphine. Provide blood and urine samples while on the inpatient unit and at follow up. Complete in-person follow up visits at 1-,2-,3-,4-, 8- and 12-weeks after leaving the hospital to measure drug use, craving, withdrawal, quality of life, and physical health.

Eligibility Criteria

This trial is for individuals aged 18-65 with opioid use disorder, specifically those using fentanyl or similar potent synthetic opioids. Participants must be willing to stay overnight in a hospital for initial treatment and provide blood and urine samples. Follow-up visits are required.

Inclusion Criteria

Meets DSM-5 criteria for OUD with at least moderate severity

Voluntarily seeking treatment for opioid use disorder (OUD)

I regularly use fentanyl or similar strong painkillers.

Exclusion Criteria

I have been treated with buprenorphine or methadone in the last 30 days.

Liver function tests > 2x the upper limit of normal

Known allergy, hypersensitivity or intolerance to buprenorphine

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants complete a brief overnight hospital stay to start treatment with either sublingual or injectable buprenorphine

1 day

1 visit (inpatient)

Treatment

Participants receive either sublingual buprenorphine or injectable buprenorphine and provide blood and urine samples

12 weeks

6 visits (in-person)

Follow-up

Participants are monitored for drug use, craving, withdrawal, quality of life, and physical health

12 weeks

6 visits (in-person)

Treatment Details

Interventions

• Buprenorphine

Trial Overview The study compares sublingual buprenorphine (Suboxone) with long-acting injectable buprenorphine to see which is better at reducing drug use and preventing relapse in opioid users. It also examines how body factors and early treatment levels affect outcomes.

Participant Groups

Group I: Injectable Buprenorphine Experimental Treatment 1 Intervention

Long-Acting Injectable Buprenorphine administered after participants receive and tolerate a single 4/1 mg sublingual buprenorphine/naloxone dose

Group II: Sublingual Buprenorphine/Naloxone Active Control 1 Intervention

Titration onto sublingual buprenorphine/naloxone (standard of care)

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?

Rachel R. Luba

Lead Sponsor

Trials

1

Recruited

60+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Findings from Research

Buprenorphine, particularly the brand-name formulations like Suboxone, has been significantly more utilized and reimbursed in Medicaid compared to other formulations, with brand-name versions dispensed 2.7 times more and costing 4.4 times more than all other formulations combined from 2002 to 2018.

Delays in the availability of generic buprenorphine formulations due to market and regulatory factors contributed to increased costs and may have hindered access to treatment for opioid use disorder during the opioid crisis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors Affecting Buprenorphine Utilization and Spending in Medicaid, 2002-2018. Barenie, RE., Sinha, MS., Kesselheim, AS.[2021]

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]

In a study of 255,726 Veterans with opioid use disorder (OUD), 15.8% received buprenorphine medication treatment (B-MOUD), with a significant increase in treatment courses over time, from 1550 in 2007 to 8146 in 2018.

Patients receiving B-MOUD had a median treatment duration of 157 days, with 33.8% undergoing multiple treatment courses, indicating that B-MOUD is a commonly utilized and persistent treatment option for managing OUD in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine use and courses of care for opioid use disorder treatment within the Veterans Health Administration. Gordon, AJ., Saxon, AJ., Kertesz, S., et al.[2023]

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]

Buprenorphine plus naloxone (Suboxone) is marketed as having a lower risk of abuse compared to buprenorphine alone (Subutex), but evidence supporting this claim is lacking, as noted in a review of the literature.

Transitioning from buprenorphine alone to the combination of buprenorphine/naloxone has not shown a decrease in risky behaviors, such as injection drug use among individuals with opioid dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comment on "a comparison of buprenorphine + naloxone to buprenorphine and methadone in the treatment of opioid dependence during pregnancy: maternal and neonatal outcomes". Newman, RG., Gevertz, SG.[2021]

Buprenorphine (Subutex) is recognized for its improved safety profile in treating opioid dependence, particularly by reducing the risk of overdose compared to other opioids.

Despite its safety advantages, there are still risks associated with the diversion of buprenorphine for misuse, as evidenced by cases of attempted intravenous injection, highlighting the need for strict dispensing protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Groin tissue necrosis requiring skin graft following parenteral abuse of buprenorphine tablets. Feeney, GF., Fairweather, P.[2013]

A study analyzing abuse trends of sublingual buprenorphine products from 2003 to 2005 found that Subutex accounted for only 7.8% of reported abuse cases, while Suboxone made up 92.2%.

The overall rate of abuse for both products was low, with an average quarterly abuse rate of 0.08 cases per 1,000 prescriptions for Subutex and 0.16 for Suboxone, indicating that these medications are relatively safe in terms of abuse potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abuse of buprenorphine in the United States: 2003-2005. Smith, MY., Bailey, JE., Woody, GE., et al.[2013]

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]

In a study of 313 opioid-dependent adults, the sublingual buprenorphine/naloxone rapidly dissolving tablet was found to be less effective than generic buprenorphine for treatment retention at day 3, with 88.3% retention compared to 95.3% for generic buprenorphine.

Despite the lower retention rate, both treatments showed similar effectiveness in reducing withdrawal symptoms and cravings, indicating that buprenorphine/naloxone is generally safe and can still help manage withdrawal despite not being non-inferior to generic buprenorphine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of a sublingual buprenorphine/naloxone rapidly dissolving tablet for the treatment of adults with opioid dependence: A randomized trial. Webster, L., Hjelmström, P., Sumner, M., et al.[2017]

Buprenorphine is a versatile medication designed for both pain relief and treatment of opioid use disorder, acting as a partial agonist at mu receptors and an antagonist at delta receptors, which helps manage pain while reducing the risk of misuse.

Various formulations of buprenorphine, including injectable, transdermal, and sublingual options, have been developed to cater to different patient needs, with specific combinations like Suboxone® including naloxone to deter misuse in opioid dependence treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine and its formulations: a comprehensive review. Poliwoda, S., Noor, N., Jenkins, JS., et al.[2022]

In a study involving 24 participants with opiate dependence, the 16 mg buprenorphine tablet formulation achieved higher serum concentrations than the 8 mg liquid solution by Day 7, indicating better pharmacokinetics for the tablet.

Despite the higher serum concentration, there were no significant differences in the physiological, subjective, or objective effects of the two formulations, suggesting that clinicians may need to adjust dosing for the tablet to achieve similar effects as the liquid solution.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, bioavailability and opioid effects of liquid versus tablet buprenorphine. Compton, P., Ling, W., Moody, D., et al.[2013]

References

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

Factors Affecting Buprenorphine Utilization and Spending in Medicaid, 2002-2018. [2021]

2. 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]

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

Buprenorphine Utilization and Prescribing Among New Jersey Medicaid Beneficiaries After Adoption of Initiatives Designed to Improve Treatment Access. [2023]

4. Ireland pubmed.ncbi.nlm.nih.gov

Buprenorphine use and courses of care for opioid use disorder treatment within the Veterans Health Administration. [2023]

5. 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]

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

Comment on "a comparison of buprenorphine + naloxone to buprenorphine and methadone in the treatment of opioid dependence during pregnancy: maternal and neonatal outcomes". [2021]

7. Australia pubmed.ncbi.nlm.nih.gov

Groin tissue necrosis requiring skin graft following parenteral abuse of buprenorphine tablets. [2013]

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

Abuse of buprenorphine in the United States: 2003-2005. [2013]

9. 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]

10. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of a sublingual buprenorphine/naloxone rapidly dissolving tablet for the treatment of adults with opioid dependence: A randomized trial. [2017]

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

Experiences and Preferences of Opioid-Use-Disorder Patients Who Switched from Brand to Generic Buprenorphine/Naloxone Films: A Case Series. [2023]

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

Buprenorphine and its formulations: a comprehensive review. [2022]

13. Ireland pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, bioavailability and opioid effects of liquid versus tablet buprenorphine. [2013]