Low-dose Buccal Buprenorphine: Relative Abuse Potential and Analgesia

Study Details

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

Study ID

NCT05988710

Start date

Oct 19, 2023

Status verified date

Jan, 2026

Completion date

Feb, 2028

Anticipated

Primary completion date

Jan, 2028

Anticipated

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Accepted

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

Study Design

Enrollment

120 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Other

Interventions and Outcome Measures

Arms

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 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.

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 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.

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 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.

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 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.

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 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.

experimental: Buccal Buprenorphine 450mcg 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 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.

Interventions

Buccal Buprenorphine 300 mcg

buprenorphine for 300mcg buccal administration

Buccal Buprenorphine 600 mcg

buprenorphine for 600mcg buccal administration

Buccal Buprenorphine 900 mcg

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 Placebo

Placebo for buccal administration

Oral Placebo

Placebo for oral administration

Oral immediate-release oxycodone 10mg

Immediate-release oxycodone for 10 mg oral administration

Buccal Buprenorphine 450mcg

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

Primary outcome measure

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 [ Time Frame: Baseline through 3.5 hours after study drug administration on each medication condition ]
Quantitative sensory testing (QST) thermal pain tolerance in seconds [ Time Frame: Baseline through 3.5 hours after study drug administration on each medication condition ]