Low-dose Buccal Buprenorphine: Relative Abuse Potential and Analgesia

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.

Study Overview

• Status: Recruiting
• Conditions: Pain; Analgesia; Abuse Opioids
• Intervention / Treatment: Drug: Buccal Buprenorphine 300 mcg; Drug: Oral Placebo; Drug: Buccal Buprenorphine 600 mcg; Drug: Buccal Buprenorphine 900 mcg; Drug: Buccal Placebo; Drug: Oral immediate-release oxycodone 10mg

• Study Type: Interventional
• Enrollment (Estimated): 72
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Daniel Larach, MD, MSTR, MA; Phone Number: 615-322-6033; Email: daniel.larach@vumc.org
• Study Contact Backup: Name: Gail Mayo; Phone Number: 6159361705; Email: gail.mayo@vumc.org

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37069
      • Recruiting
      • Vanderbilt University Medical Center
      • Contact: Gail Mayo; Phone Number: 6159361705; Email: gail.mayo@vumc.org
      • Contact: Daniel Larach Larach, MD, MSTR, MA; Phone Number: 615-322-6033; Email: daniel.larach@vumc.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Buccal Buprenorphine 300mcg and oral Placebo; 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 600 mcg and oral placebo, 3) Buccal buprenorphine 900 mg and oral placebo, 4) oral immediate-release oxycodone 10mg and oral placebo, or 5) buccal placebo and oral placebo.	Drug: Buccal Buprenorphine 300 mcg; buprenorphine for 300mcg buccal administration; Drug: Oral Placebo; Placebo for oral administration
Experimental: Buccal Buprenorphine 600mcg and oral Placebo; 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 600 mcg and oral placebo, 3) Buccal buprenorphine 900 mg and oral placebo, 4) oral immediate-release oxycodone 10mg and oral placebo, or 5) buccal placebo and oral placebo.	Drug: Oral Placebo; Placebo for oral administration; Drug: Buccal Buprenorphine 600 mcg; buprenorphine for 600mcg buccal administration
Experimental: Buccal Buprenorphine 900mcg and oral Placebo; 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 600 mcg and oral placebo, 3) Buccal buprenorphine 900 mg and oral placebo, 4) oral immediate-release oxycodone 10mg and oral placebo, or 5) buccal placebo and oral placebo.	Drug: Oral Placebo; Placebo for oral administration; Drug: Buccal Buprenorphine 900 mcg; buprenorphine for 900mcg buccal administration
Active Comparator: Oral immediate release oxycodone 10mg and buccal placebo; 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 600 mcg and oral placebo, 3) Buccal buprenorphine 900 mg and oral placebo, 4) oral immediate-release oxycodone 10mg and oral placebo, or 5) buccal placebo and oral placebo.	Drug: Buccal Placebo; Placebo for buccal administration; Drug: Oral immediate-release oxycodone 10mg; Immediate-release oxycodone for 10 mg oral administration
Placebo Comparator: Oral placebo and buccal placebo; 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 600 mcg and oral placebo, 3) Buccal buprenorphine 900 mg and oral placebo, 4) oral immediate-release oxycodone 10mg and oral placebo, or 5) buccal placebo and oral placebo.	Drug: Oral Placebo; Placebo for oral administration; Drug: Buccal Placebo; Placebo for buccal administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in mean maximum effect score (Emax) of the drug liking visual analog scale between equianalgesic dose of buprenorphine and placebo conditions	Difference in mean maximum effect score (Emax) of the drug liking visual analog scale between equianalgesic dose of buprenorphine and placebo 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
Difference in mean maximum effect score (Emax) of the drug liking visual analog scale between oxycodone 10 mg and placebo conditions	Difference in mean maximum effect score (Emax) of the drug liking visual analog scale between oxycodone 10 mg and placebo 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
QST heat pain threshold	Mean time in seconds elapsed from onset of the thermal stimulus to the point at which heat stimulus is first experienced as painful. Thermal pain threshold is an indicator of pain sensitivity.	Baseline through 3.5 hours after study drug administration on each medication condition
Visual Analog Scale (VAS) pain intensity	Difference in mean Emax of the pain intensity VAS between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo. The VAS pain intensity is a measure of experienced pain intensity on 0 to 100 scale when 0 is no pain and 100 is worst pain imaginable.	Baseline through 3.5 hours after study drug administration on each medication condition
VAS pain unpleasantness	Difference in mean Emax of the pain unpleasantness VAS between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo. The VAS pain unpleasantness is a measure of experienced pain unpleasantness on 0 to 100 scale, when 0 is no unpleasantness and 100 is most unpleasant imaginable.	Baseline through 3.5 hours after study drug administration on each medication condition
McGill Pain Questionnaire - Short Form	Mean of maximum McGill Pain Questionnaire - Short Form score between oxycodone 10mg, equianalgesic dose of buprenorphine and placebo. The score ranges from 0-33 where 0 represents no pain and 33 represents most intense pain. Positive change values indicate decreased pain responsiveness.	Baseline through 3.5 hours after study drug administration on each medication condition
VAS alertness/drowsiness	Difference in mean Emax of the VAS alertness/drowsiness between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo. The VAS alertness/drowsiness assesses alertness and drowsiness following drug administration on 0 to 100 sale, when 0 is extreme drowsiness, 50 is neutral, and 100 is extreme alertness.	Baseline through 3.5 hours after study drug administration on each medication condition
VAS any drug effects	Difference in mean Emax of the VAS any drug effects between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo. VAS any drug effects assesses presence of any drug effects felt by participant on 0 to 100 scale, when 0 is no drug effects and 100 is extreme drug effects.	Baseline through 3.5 hours after study drug administration on each medication condition
VAS good effects	Difference in mean Emax of the VAS good effects between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo. VAS good effects assesses presence of drug effects characterized as good felt by participant on scale 0 to 100 when 0 is no good drug effects and 100 is extreme good drug effects.	Baseline through 3.5 hours after study drug administration on each medication condition
VAS feeling high	Difference in mean Emax of the VAS feeling high between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo. VAS feeling high assesses presence of "feeling high" by participant on 0 to 100 scale when o is not feeling high at all and 100 is feeling extremely high.	Baseline through 3.5 hours after study drug administration on each medication condition
VAS bad effects	Difference in mean Emax of the VAS bad effects between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo. VAS bad effects assesses presence of drug effects characterized as bad felt by participant on 0 to 100 scale when 0 is no bad drug effects and 100 is extreme bad drug effects.	Baseline through 3.5 hours after study drug administration on each medication condition
VAS desire to use opioids	Difference in mean Emax of the VAS desire to use opioids between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo. VAS desire to use opioids assesses participant's desire to use opioids on a 0-100 scale when 0 is no desire to use opioids and 100 is extreme desire to use opioids.	Baseline through 3.5 hours after study drug administration on each medication condition
Opioid Adjective Rating Scale	Difference in mean Emax of the VAS Opioid Adjective Rating Scale between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo. VAS Opioid Adjective Rating Scale is a 12 item questionnaire which evaluates common sensory and somatic effects of opioid (e.g., itching, vomiting, sweating, nausea, dry mouth). Each effect is rated on 0 to 4 scale when 0 is not at all and 4 is extremely.	Baseline through 3.5 hours after study drug administration on each medication condition
Temporal summation of pain (TSP)	Change in pain intensity between first and most painful TSP stimuli (mean of two TSP trials) compared between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo conditions. Pain intensity will be measured on a 0-10 Numeric Rating Scale when when 0 is no pain and 100 is worst pain imaginable.	Baseline through 3.5 hours after study drug administration on each medication condition

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Daniel Larach, MD, MSTR, MA, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2023
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: August 1, 2023
• First Submitted That Met QC Criteria: August 8, 2023
• First Posted (Actual): August 14, 2023

Study Record Updates

• Last Update Posted (Actual): October 27, 2023
• Last Update Submitted That Met QC Criteria: October 26, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Perceptual Disorders; Agnosia; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Narcotic Antagonists; Buprenorphine; Oxycodone
• Other Study ID Numbers: 222204; 1K23DA057387 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No