Buccal Buprenorphine vs. Oxycodone for Pain

Overseen By Gail Mayo

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Vanderbilt University Medical Center

Must not be taking: Benzodiazepines, Opioids, Marijuana, others

Disqualifiers: Liver/kidney disease, Chronic pain, Pregnancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 5 weeks

120 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this study is to compare the abuse potential of low-dose equianalgesic buccal buprenorphine to a commonly used full mu opioid receptor (MOR) agonist in a highly controlled experimental setting. This is a translational study in which healthy participants are phenotyped for psychosocial and Opioid-Use-Disorder-risk-related metrics. In a within-subjects crossover design, 60 participants will receive a standard postoperative oral oxycodone dose (10 mg), placebo, and 3 different doses of buccal buprenorphine across 5 separate sessions. Quantitative Sensory Testing (QST) will be used to evaluate alterations in pain responsiveness relative to placebo across buprenorphine doses and oxycodone, and will compare abuse potential (indexed by the standard FDA drug liking metric) following equianalgesic doses of the two drugs.

Will I have to stop taking my current medications?

The trial requires participants to be opioid-naive, meaning you must not have used certain opioid medications in the past 3 months. Additionally, you cannot have recently used medications that might interfere with the study drugs, benzodiazepines, or certain other substances.

What data supports the effectiveness of buccal buprenorphine for pain management?

Buccal buprenorphine has been shown to be effective in managing moderate to severe chronic low back pain in patients who have not previously used opioids, according to a study that evaluated its use for around-the-clock pain relief. ^{1 2 3 4 5}

Is buccal buprenorphine generally safe for humans?

Buccal buprenorphine is generally well tolerated and offers effective pain relief with fewer safety risks compared to other opioids, and no cases of respiratory depression (breathing problems) were reported in the studies reviewed. ^{2 3 4 6 7}

What makes buccal buprenorphine unique for pain management?

Buccal buprenorphine is unique because it uses a special film that dissolves in the mouth, providing effective and continuous pain relief with fewer safety risks compared to other opioids. It is particularly noted for not causing respiratory depression, a common risk with other opioid treatments. ^{2 3 4 6 8}

Research Team

Daniel Larach, MD, MSTR, MA

Principal Investigator

Vanderbilt University Medical Center

Eligibility Criteria

This trial is for healthy adults aged 18-65 who can consent and have not used opioids in the last three months. It's not for those with severe mental health issues, substance use disorders, chronic pain, liver/kidney disease, seizure disorders, or recent drug use that could affect the study.

Inclusion Criteria

I am mentally capable of understanding and agreeing to the trial.

Ability to read and write in English sufficiently to understand and complete study questionnaires

I am between 18 and 65 years old.

Exclusion Criteria

I have recently used benzodiazepines or opioids.

I am not taking medications that could affect the study drug.

I have liver or kidney disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive buccal buprenorphine and oral placebo in a crossover design across 5 sessions approximately 5 days apart

5 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Buccal Buprenorphine
• Buccal Placebo
• Oral immediate-release oxycodone
• Oral Placebo

Trial Overview The study tests if low-dose buccal buprenorphine (placed between cheek and gum) has less potential for abuse compared to oral oxycodone while still providing pain relief. Participants will try different doses of buprenorphine, a placebo, and oxycodone in separate sessions.

Participant Groups

Group I: Buccal Buprenorphine 900mcg and oral Placebo Experimental Treatment 2 Interventions

In randomized order (crossover) across 5 laboratory sessions approximately 5 days apart, participants will receive: 1) Buccal buprenorphine 300 mcg and oral placebo, 2) Buccal buprenorphine 450 mcg and oral placebo 3) Buccal buprenorphine 600 mcg and oral placebo, 4) Buccal buprenorphine 900 mg and oral placebo, 5) oral immediate-release oxycodone 10mg and oral placebo, or 6) buccal placebo and oral placebo.

Group II: Buccal Buprenorphine 600mcg and oral Placebo Experimental Treatment 2 Interventions

In randomized order (crossover) across 5 laboratory sessions approximately 5 days apart, participants will receive: 1) Buccal buprenorphine 300 mcg and oral placebo, 2) Buccal buprenorphine 450 mcg and oral placebo 3) Buccal buprenorphine 600 mcg and oral placebo, 4) Buccal buprenorphine 900 mg and oral placebo, 5) oral immediate-release oxycodone 10mg and oral placebo, or 6) buccal placebo and oral placebo.

Group III: Buccal Buprenorphine 450mcg and oral Placebo Experimental Treatment 2 Interventions

In randomized order (crossover) across 5 laboratory sessions approximately 5 days apart, participants will receive: 1) Buccal buprenorphine 300 mcg and oral placebo, 2) Buccal buprenorphine 450 mcg and oral placebo 3) Buccal buprenorphine 600 mcg and oral placebo, 4) Buccal buprenorphine 900 mg and oral placebo, 5) oral immediate-release oxycodone 10mg and oral placebo, or 6) buccal placebo and oral placebo.

Group IV: Buccal Buprenorphine 300mcg and oral Placebo Experimental Treatment 2 Interventions

In randomized order (crossover) across 5 laboratory sessions approximately 5 days apart, participants will receive: 1) Buccal buprenorphine 300 mcg and oral placebo, 2) Buccal buprenorphine 450 mcg and oral placebo 3) Buccal buprenorphine 600 mcg and oral placebo, 4) Buccal buprenorphine 900 mg and oral placebo, 5) oral immediate-release oxycodone 10mg and oral placebo, or 6) buccal placebo and oral placebo.

Group V: Oral immediate release oxycodone 10mg and buccal placebo Active Control 2 Interventions

In randomized order (crossover) across 5 laboratory sessions approximately 5 days apart, participants will receive: 1) Buccal buprenorphine 300 mcg and oral placebo, 2) Buccal buprenorphine 450 mcg and oral placebo 3) Buccal buprenorphine 600 mcg and oral placebo, 4) Buccal buprenorphine 900 mg and oral placebo, 5) oral immediate-release oxycodone 10mg and oral placebo, or 6) buccal placebo and oral placebo.

Group VI: Oral placebo and buccal placebo Placebo Group 2 Interventions

In randomized order (crossover) across 5 laboratory sessions approximately 5 days apart, participants will receive: 1) Buccal buprenorphine 300 mcg and oral placebo, 2) Buccal buprenorphine 450 mcg and oral placebo 3) Buccal buprenorphine 600 mcg and oral placebo, 4) Buccal buprenorphine 900 mg and oral placebo, 5) oral immediate-release oxycodone 10mg and oral placebo, or 6) buccal placebo and oral placebo.

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

Approved in United States as Belbuca for:

• Chronic pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate

Approved in United States as Butrans for:

• Management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate

Approved in United States as Subutex for:

• Treatment of opioid addiction

Approved in United States as Suboxone for:

• Treatment of opioid addiction

Approved in European Union as Buprenorphine for:

• Treatment of opioid dependence
• Severe chronic pain

Approved in Canada as Buprenorphine for:

• Management of opioid dependence
• Chronic pain

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Findings from Research

Buprenorphine, administered sublingually and buccally, showed significant bioavailability (51.4% and 27.8%, respectively) in a study involving six healthy men with a history of heroin use, indicating effective absorption through these routes.

The study found that the elimination half-lives of buprenorphine were longer for sublingual and buccal routes compared to intravenous administration, suggesting a potential depot effect where the drug is retained in the oral mucosa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human pharmacokinetics of intravenous, sublingual, and buccal buprenorphine. Kuhlman, JJ., Lalani, S., Magluilo, J., et al.[2019]

Buprenorphine HCl buccal film (BBUP) significantly reduced pain in opioid-naive patients with chronic low back pain, showing a greater reduction in pain scores compared to placebo after 12 weeks of treatment.

BBUP was well tolerated, with common side effects including nausea and constipation, and a higher percentage of patients experienced at least a 30% reduction in pain compared to those on placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of buccal buprenorphine in opioid-naive patients with moderate to severe chronic low back pain. Rauck, RL., Potts, J., Xiang, Q., et al.[2022]

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]

Long-acting buprenorphine formulations, including CAM 2038 (Buvidal), RBP-6000 (Sublocade™), and Probuphine™, provide effective options for treating opioid use disorders (OUDs) with varying administration schedules, such as weekly, monthly, or every six months.

These depot and implant formulations enhance patient adherence to treatment by reducing the frequency of dosing compared to traditional oral or sublingual medications, potentially improving overall outcomes in managing OUDs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent advances in the treatment of opioid use disorders-focus on long-acting buprenorphine formulations. Soyka, M., Franke, AG.[2021]

After switching from sublingual buprenorphine-naloxone (SLBN) to buccal buprenorphine-naloxone (BBN), there was a significant decrease in overall buprenorphine-naloxone prescriptions by 68%, leading to approximately $3.5 million in quarterly savings for the Medicaid plan.

Toxicology results indicated a notable reduction in drug positivity for opioids and cocaine, suggesting improved adherence to treatment protocols and potentially less misuse or diversion of the medication following the switch to BBN.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decline in Buprenorphine/Naloxone Prescriptions in a State Medicaid Population Following Formulary Conversion from Suboxone to Bunavail. Soper, R., Appajosyula, S., Deximo, C.[2019]

Buprenorphine buccal film provides effective and continuous pain relief with a favorable safety profile, as no cases of respiratory depression were reported in the clinical studies reviewed.

Due to its superior bioavailability and tolerability, buprenorphine buccal film is recommended as a first-line treatment for chronic pain compared to other formulations and opioids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine buccal film for chronic pain management. Hale, M., Gimbel, J., Rauck, R.[2021]

Buccal delivery of prodrugs of opioid analgesics like nalbuphine and naloxone can significantly improve their bioavailability, achieving up to 90% in rats and 35-50% in dogs, compared to less than 5% when taken orally.

The prodrugs were designed to eliminate the bitter taste associated with these opioids, which improved patient compliance and did not cause any adverse effects during administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved buccal delivery of opioid analgesics and antagonists with bitterless prodrugs. Hussain, MA., Aungst, BJ., Koval, CA., et al.[2019]

Buprenorphine is a promising long-term treatment for chronic pain due to its unique properties, including a ceiling effect on respiratory suppression and reduced impact on the immune and endocrine systems compared to other opioids.

A novel method of introducing buprenorphine without the traditional opioid-free withdrawal period was successful in a case series, allowing for immediate treatment of opioid-dependent patients without causing precipitated withdrawal or significant adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transdermal buprenorphine, opioid rotation to sublingual buprenorphine, and the avoidance of precipitated withdrawal: a review of the literature and demonstration in three chronic pain patients treated with butrans. Kornfeld, H., Reetz, H.[2015]

References

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

Human pharmacokinetics of intravenous, sublingual, and buccal buprenorphine. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of buccal buprenorphine in opioid-naive patients with moderate to severe chronic low back pain. [2022]

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

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

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

Recent advances in the treatment of opioid use disorders-focus on long-acting buprenorphine formulations. [2021]

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

Decline in Buprenorphine/Naloxone Prescriptions in a State Medicaid Population Following Formulary Conversion from Suboxone to Bunavail. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Buprenorphine buccal film for chronic pain management. [2021]

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

Improved buccal delivery of opioid analgesics and antagonists with bitterless prodrugs. [2019]

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

Transdermal buprenorphine, opioid rotation to sublingual buprenorphine, and the avoidance of precipitated withdrawal: a review of the literature and demonstration in three chronic pain patients treated with butrans. [2015]