Low-dose Buccal Buprenorphine: Relative Abuse Potential and Analgesia

NCT05988710 | Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: 2222041K23DA057387
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Analgesia; Abuse Opioids; Pain

Outcome Measures

Primary Outcomes (2)

• Difference in mean maximum effect score (Emax) of the drug liking visual analog scale (VAS) between oxycodone 10 mg and an equianalgesic dose of buprenorphine

  Difference in mean Emax of the drug liking VAS between oxycodone 10 mg and an equianalgesic dose of buprenorphine conditions. Drug liking VAS is a bipolar scale designed to assess a participant's liking for a given study intervention at the time the question is being asked (that is, at this moment). It is scored as an integer ranging from 0 (strong disliking) to 100 (strong liking).

  Baseline through 3.5 hours after study drug administration on each medication condition

• Quantitative sensory testing (QST) thermal pain tolerance in seconds

  Mean time in seconds elapsed from onset of the heat pain stimulus to participants withdrawal from the stimulus. Heat pain tolerance is an indicator of pain sensitivity. This will determine the equianalgesic dose of buccal buprenorphine compared to oxycodone 10 mg. Equivalence to oxycodone will be defined as the buprenorphine does that produces a mean thermal pain tolerance increase within 0.5 standard deviation of the oxycodone. response.

  Baseline through 3.5 hours after study drug administration on each medication condition

Secondary Outcomes (14)

• Difference in mean maximum effect score (Emax) of the drug liking visual analog scale between equianalgesic dose of buprenorphine and placebo conditions

  Baseline through 3.5 hours after study drug administration on each medication condition

• Difference in mean maximum effect score (Emax) of the drug liking visual analog scale between oxycodone 10 mg and placebo conditions

  Baseline through 3.5 hours after study drug administration on each medication condition

• QST heat pain threshold

  Baseline through 3.5 hours after study drug administration on each medication condition

• Visual Analog Scale (VAS) pain intensity

  Baseline through 3.5 hours after study drug administration on each medication condition

• VAS pain unpleasantness

  Baseline through 3.5 hours after study drug administration on each medication condition

Study Arms (6)

Buccal Buprenorphine 300mcg and oral Placebo

EXPERIMENTAL

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.

Drug: Buccal Buprenorphine 300 mcg; Drug: Oral Placebo

Buccal Buprenorphine 600mcg and oral Placebo

EXPERIMENTAL

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.

Drug: Buccal Buprenorphine 600 mcg; Drug: Oral Placebo

Buccal Buprenorphine 900mcg and oral Placebo

EXPERIMENTAL

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.

Drug: Buccal Buprenorphine 900 mcg; Drug: Oral Placebo

Oral immediate release oxycodone 10mg and buccal placebo

ACTIVE COMPARATOR

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.

Drug: Buccal Placebo; Drug: Oral immediate-release oxycodone 10mg

Oral placebo and buccal placebo

PLACEBO COMPARATOR

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.

Drug: Buccal Placebo; Drug: Oral Placebo

Buccal Buprenorphine 450mcg and oral Placebo

EXPERIMENTAL

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.

Drug: Oral Placebo; Drug: Buccal Buprenorphine 450mcg

Interventions

Buccal Buprenorphine 300 mcg DRUG

buprenorphine for 300mcg buccal administration

Buccal Buprenorphine 300mcg and oral Placebo

Buccal Buprenorphine 600 mcg DRUG

buprenorphine for 600mcg buccal administration

Buccal Buprenorphine 600mcg and oral Placebo

Buccal Buprenorphine 900 mcg DRUG

buprenorphine for 900mcg buccal administration. Note: This arm has been discontinued as of 06/25/2024 and has been replaced with the 450mcg buprenorphine buccal administration arm.

Buccal Buprenorphine 900mcg and oral Placebo

Buccal Placebo DRUG

Placebo for buccal administration

Oral immediate release oxycodone 10mg and buccal placebo; Oral placebo and buccal placebo

Oral Placebo DRUG

Placebo for oral administration

Buccal Buprenorphine 300mcg and oral Placebo; Buccal Buprenorphine 450mcg and oral Placebo; Buccal Buprenorphine 600mcg and oral Placebo; Buccal Buprenorphine 900mcg and oral Placebo; Oral placebo and buccal placebo

Oral immediate-release oxycodone 10mg DRUG

Immediate-release oxycodone for 10 mg oral administration

Oral immediate release oxycodone 10mg and buccal placebo

Buccal Buprenorphine 450mcg DRUG

buprenorphine for 450mcg buccal administration. Note: This arm has been added to replace the 900mcg buprenorphine buccal administration arm.

Buccal Buprenorphine 450mcg and oral Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37069, United States

RECRUITING

MeSH Terms

Conditions

Agnosia; Opioid-Related Disorders; Pain

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Study Officials

• Daniel Larach, MD, MSTR, MA

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Daniel Larach, MD, MSTR, MA

CONTACT

615-322-6033; daniel.larach@vumc.org

Gail Mayo

CONTACT

6159361705; gail.mayo@vumc.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Asst Professor of Anesthesiology

Model Details: randomized, double blind, double-dummy, placebo-controlled, crossover

Study Record Dates

• First Submitted: August 1, 2023
• First Posted: August 14, 2023
• Study Start: October 19, 2023
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): February 1, 2028
• Last Updated: January 12, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)