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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to compare a low-dose buccal (inside the cheek) form of buprenorphine, a pain relief medication, to oxycodone regarding potential misuse and pain relief. Participants will try various doses of buprenorphine and a standard dose of oxycodone to evaluate their experiences and the effects on their pain. The study seeks individuals who have not recently used opioids and do not have chronic pain or specific health issues like liver or kidney disease. As a Phase 4 trial, this research helps determine how the FDA-approved treatment benefits a broader range of patients.

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 is the safety track record for these treatments?

Research has shown that buccal buprenorphine is generally safe for use. It effectively manages long-term pain without causing serious side effects like breathing problems, a common concern with opioid medications.

Oral immediate-release oxycodone, approved by the FDA, is commonly used to treat moderate to severe pain. While effective, it can sometimes cause side effects such as dizziness, nausea, or constipation. Both medications have undergone thorough testing in many studies, providing strong safety information.

For those considering joining a trial with these medications, it's important to know they have been well-studied and are considered safe for many people. However, since individual responses vary, discussing any concerns with a healthcare provider is always advisable. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Buccal buprenorphine is unique because it offers a fresh approach to managing pain, distinct from more common opioids like oxycodone. Unlike traditional oral painkillers, buccal buprenorphine is administered through the inside of the cheek, which can result in faster absorption and potentially fewer side effects. Researchers are excited about this treatment because it combines the potent pain-relieving effects of buprenorphine with a less invasive delivery method, potentially offering a safer alternative to current opioid options.

What evidence suggests that this trial's treatments could be effective for pain?

This trial will compare buccal buprenorphine and oral immediate-release oxycodone for pain management. Studies have shown that buccal buprenorphine effectively manages chronic pain, providing continuous relief without causing breathing problems. Research indicates it significantly reduces pain levels. In contrast, oral immediate-release oxycodone is a well-known treatment for moderate to severe pain and is highly effective for various pain conditions. Both treatments relieve pain but operate differently. Oxycodone fully activates pain-relieving receptors, while buccal buprenorphine partially activates them, offering pain relief with potentially a lower risk of addiction. ^{2 3 4 5 6}

Who Is on the Research Team?

Daniel Larach, MD, MSTR, MA

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

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 haven't taken any opioid medications in the last 3 months.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6917545/

Safety And Efficacy Of The Unique Opioid Buprenorphine ... Transdermal buprenorphine has thus been clinically shown to be effective in managing chronic pain in a manner similar to that of the Schedule II opioids ...

2. belbuca.com belbuca.com/hcp/efficacy-safety/

Clinical Efficacy in Severe and Persistent Pain Management Study participants experienced a reduction in pain score from ~7 to ~3 during the open-label titration phase.1,2‡. Double-blind treatment: Patients were ...

3. tandfonline.com tandfonline.com/doi/full/10.2217/pmt-2020-0013

Buprenorphine Buccal Film for Chronic Pain Management Buprenorphine buccal film offers effective and continuous pain relief that is generally well tolerated, with no cases of respiratory depression reported in any ...

4. va.gov va.gov/formularyadvisor/DOC_PDF/CRE_Buprenorphine_for_Chronic_Pain_MAR_2024.pdf

Buprenorphine for Management of Chronic Pain buprenorphine showed some effectiveness as a chronic pain analgesic, the ... Efficacy and tolerability of buccal buprenorphine in opioid-naïve patients ...

5. mayoclinic.org mayoclinic.org/drugs-supplements/buprenorphine-buccal-mucosa-route-sublingual-route/description/drg-20074237

Buprenorphine (buccal mucosa route, sublingual route) Buprenorphine buccal film is used to relieve pain severe enough to require daily, around-the-clock, long-term opioid treatment.

6. belbuca.com belbuca.com/hcp/tolerability/

Safety and Clinical Data There were no reports of respiratory depression in the pivotal phase 3 clinical studies of BELBUCA, including the long-term safety study.2,4.