Low-dose Buccal Buprenorphine: Relative Abuse Potential and Analgesia

Vanderbilt University Medical Center

Status and phase: Enrolling; Phase 4

Conditions: Abuse Opioids; Analgesia; Pain

Treatments: Drug: Buccal Buprenorphine 450mcg; Drug: Buccal Placebo; Drug: Buccal Buprenorphine 300 mcg; Drug: Oral Placebo; Drug: Buccal Buprenorphine 900 mcg; Drug: Buccal Buprenorphine 600 mcg; Drug: Oral immediate-release oxycodone 10mg

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05988710

1K23DA057387 (U.S. NIH Grant/Contract)

222204

Details and patient eligibility

About

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.

Enrollment: 120 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Intact cognitive status and ability to provide informed consent
• Ability to read and write in English sufficiently to understand and complete study questionnaires
• Age 18-65
• Opioid-naive status (defined as no use of full mu-opioid receptor (MOR) agonist, partial MOR agonist, or mixed agonist/antagonist medications for the prior 3 months by patient report

Exclusion criteria

• Liver/kidney disease
• Chronic pain
• Current/prior substance use disorder
• Pregnancy (to avoid fetal drug exposure, with pregnancy tests conducted to confirm eligibility)
• Seizure disorder
• Certain psychiatric conditions (severe depression, bipolar disorder, psychotic disorders)
• Recent use of medications that may interfere with study drug metabolism
• Recent benzodiazepine or opioid use (confirmed via rapid urine screening prior to each lab session)
• The presence of any medical conditions felt by the study physician to render participant unsafe
• Prior allergic reaction or intolerance to oxycodone, buprenorphine, or their analogs (explicitly including moderate-to-severe nausea or vomiting with prior opioids)
• Recent use of marijuana, delta-8 THC, CBD, and similar products
• Recent use of kratom
• Severe asthma
• Long QT syndrome
• Parkinson disease
• Weight <60 kg

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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120 participants in 6 patient groups, including a placebo group

Buccal Buprenorphine 300mcg and oral Placebo

Experimental group

Description:

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.

Treatment:

Drug: Oral Placebo

Drug: Buccal Buprenorphine 300 mcg

Buccal Buprenorphine 600mcg and oral Placebo

Experimental group

Description:

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.

Treatment:

Drug: Oral Placebo

Drug: Buccal Buprenorphine 600 mcg

Buccal Buprenorphine 900mcg and oral Placebo

Experimental group

Description:

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.

Treatment:

Drug: Oral Placebo

Drug: Buccal Buprenorphine 900 mcg

Oral immediate release oxycodone 10mg and buccal placebo

Active Comparator group

Description:

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.

Treatment:

Drug: Oral immediate-release oxycodone 10mg

Drug: Buccal Placebo

Oral placebo and buccal placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Oral Placebo

Drug: Buccal Placebo

Buccal Buprenorphine 450mcg and oral Placebo

Experimental group

Description:

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.

Treatment:

Drug: Oral Placebo

Drug: Buccal Buprenorphine 450mcg