Low-dose Buccal Buprenorphine: Relative Abuse Potential and Analgesia
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- 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
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Buccal Buprenorphine 300 mcg (Drug)
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.
干预措施: Oral Placebo (Drug)
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.
干预措施: Buccal Buprenorphine 600 mcg (Drug)
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.
干预措施: Oral Placebo (Drug)
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.
干预措施: Buccal Buprenorphine 900 mcg (Drug)
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.
干预措施: Oral Placebo (Drug)
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.
干预措施: Buccal Placebo (Drug)
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.
干预措施: Oral immediate-release oxycodone 10mg (Drug)
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.
干预措施: Buccal Placebo (Drug)
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.
干预措施: Oral Placebo (Drug)
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.
干预措施: Oral Placebo (Drug)
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.
干预措施: Buccal Buprenorphine 450mcg (Drug)
结局指标
主要结局
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
时间窗: Baseline through 3.5 hours after study drug administration on each medication condition
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).
Quantitative sensory testing (QST) thermal pain tolerance in seconds
时间窗: Baseline through 3.5 hours after study drug administration on each medication condition
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.
次要结局
- 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)
- McGill Pain Questionnaire - Short Form(Baseline through 3.5 hours after study drug administration on each medication condition)
- VAS alertness/drowsiness(Baseline through 3.5 hours after study drug administration on each medication condition)
- VAS any drug effects(Baseline through 3.5 hours after study drug administration on each medication condition)
- VAS good effects(Baseline through 3.5 hours after study drug administration on each medication condition)
- VAS feeling high(Baseline through 3.5 hours after study drug administration on each medication condition)
- VAS bad effects(Baseline through 3.5 hours after study drug administration on each medication condition)
- VAS desire to use opioids(Baseline through 3.5 hours after study drug administration on each medication condition)
- Opioid Adjective Rating Scale(Baseline through 3.5 hours after study drug administration on each medication condition)
- Temporal summation of pain (TSP)(Baseline through 3.5 hours after study drug administration on each medication condition)
研究者
Daniel Larach
Asst Professor of Anesthesiology
Vanderbilt University Medical Center