A Randomized, Double-Blind, Placebo- and Active-Controlled, Crossover Study to Evaluate the Abuse Potential of Oxymorphone Compared to Other Mu Opioid Agonists in Physically Dependent Opioid Users With Moderate-to-Severe Opioid Use Disorder
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 2
- 主要终点
- Positive Subjective Drug Effects (i.e., Drug "Liking").
研究概览
简要总结
Significant public health concerns have arisen from the intravenous misuse of oxymorphone, a potent mu-opioid pain medication. However, little is known about its abuse potential relative to other mu-opioid analgesics. The present study is designed to examine the abuse liability of intravenous oxymorphone compared to other mu opioid agonists (oxycodone, and hydromorphone) among physically dependent opioid abusers.
详细描述
Significant public health concerns have arisen from the misuse of oxymorphone, a potent mu-opioid pain medication approved by the Food and Drug Administration as Opana and Opana ER. However, little is known about its abuse potential relative to other mu opioid analgesics. The present study is designed to examine the abuse liability of intravenous oxymorphone compared to other mu opioid agonists (oxycodone and hydromorphone). Participants who are physically dependent on opioids and who meet DSM 5 criteria for Opioid Use Disorder will complete the study across 2 sites, New York State Psychiatric Institute (NYSPI) and the University of Kentucky; a total of 6 additional participants across 2 sites will complete a pilot phase of the study in order to establish comparable opioid dose-response functions based on subjective ratings of Drug Liking. All participants will reside in clinical inpatient units for the duration of the studies (both the 8- to 9-week main and 4- to 5-week pilot studies; please note that the pilot study is identical in design to the first 4-5 weeks of the main study). The study design is based on the 2017 FDA Assessment of Abuse Potential of Drugs: Guidance for Industry [Center for Drug Evaluation and Research (CDER), 2017], which suggests the use of a double-blind, positive- and placebo-controlled design that includes a qualification phase and VAS measure of Drug Liking. The proposed study also examines the reinforcing effects of oxymorphone and other mu opioid agonists using two different drug self-administration procedures, namely Drug versus Money and Drug versus Drug choice procedures.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 21 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able to understand and provide signed and dated written consent.
- •Self-reported opioid use for nontherapeutic purposes on at least 21 days in the 30 days prior to screening, physical dependence on opioids, recent intravenous opioid use, and meeting DSM 5 criteria for moderate-severe opioid use disorder.
- •Positive urine drug screen for opioids (those who are in a methadone or buprenorphine treatment program are ineligible; physical dependence on street methadone or buprenorphine are also exclusionary so participants must produce at least one methadone- or buprenorphine-negative urine during screening).
- •≥ 21 and ≤ 55 years of age.
- •Body mass index (BMI) ≥ 18 and ≤ 35 kg/m2 and weight ≥ 50 kg (110 pounds).
- •Otherwise healthy as determined by the investigator.
- •Demonstrate understanding how to complete the self-administration tasks and VAS Questionnaire.
- •Women of childbearing potential must not be pregnant or breastfeeding at screening.
- •Willing and able to comply with all testing requirements defined in the protocol.
- •participation in the Study Treatment Phase:
- •During the Study Qualification Phase, on the bipolar 100--mm Drug Liking VAS, the subject must provide Emax ≥ 40 mm and < 60 mm following placebo and, following morphine 56 mg/70 kg, i.v., Emax ≥ 60 mm and ≥ 15 mm closer to "Strong Liking" than the Emax to placebo.
- •In the judgment of the investigator, the subject is able to tolerate the i.v., opioids administered in the study, including the ability to complete most pharmacodynamics assessments administered post--dose.
- •In the judgment of the study staff, the subject's general behavior during the Study Qualification Phase suggests the ability to successfully complete the Study Treatment Phase.
排除标准
- •History of a medical or psychiatric disorder that would prevent successful completion of the study.
- •Current DSM-5 diagnosis of substance use disorders requiring medical management other than OUD.
- •Suicidal ideation or intent with or without a plan at Screening or within 6 months prior to Screening (i.e., answering "Yes" to questions 4 and/or 5 on the Suicidal Ideation section of the Columbia Suicide Severity Rating Scale).
- •Currently seeking or participating in treatment for substance use disorder.
- •Physically dependent on drugs of abuse (other than opioids, nicotine, or caffeine) or alcohol.
- •Medically important deviation from normal limits on physical examination, vital signs, screening laboratory tests, or 12--lead ECG.
- •Significant cardiovascular, hepatic, renal, respiratory, gastrointestinal, endocrine, immunologic, dermatologic, hematologic, or neurologic disorder.
- •Any surgical, or medical condition that may interfere with the absorption, distribution, metabolism, or excretion of the test drug.
- •Family history of long QT syndrome and/or unexpected sudden cardiac death or is known to have QTc > 500 ms at screening.
- •Used an investigational agent within 30 days or 5 therapeutic half-lives of that agent, whichever is longer, prior to the first dose of study drug.
- •Hypersensitivity to opioids or any drug intended for use in this study.
- •Acute gastrointestinal symptoms (e.g., nausea, vomiting, fever, or Diarrhea unrelated to opioid withdrawal) ≤ 7 days before Day
- •Any of the following values for laboratory tests at Screening:
- •A positive pregnancy test in women of childbearing potential.
- •Hemoglobin < 11 g/dL in males and < 10 gm/dL in females.
- •Neutrophil count < 1.0 × 109/L.
- •Platelet count < 75 × 109/L.
- •Creatinine clearance < 50 ml/min per modified Cockcroft-Gault equation.
- •Aspartate aminotransferase or alanine aminotransferase > 3.0x upper limit of normal.
研究组 & 干预措施
Intravenous Challenge Drug: Oxymorphone
Intravenous (IV) Dose Range: 1.8, 3.2, 5.6, 10 mg/70kg of the participant's body weight
干预措施: Intravenous Challenge Drug (Drug)
Intravenous Challenge Drug: Oxycodone
IV Dose Range: 10, 18, 32, 56 mg/70kg of the participant's body weight
干预措施: Intravenous Challenge Drug (Drug)
Intravenous Challenge Drug: Hydromorphone
IV Dose Range: 3.2, 5.6, 10, 18 mg/70kg of the participant's body weight
干预措施: Intravenous Challenge Drug (Drug)
Intravenous Challenge Drug: Placebo
IV saline
干预措施: Intravenous Challenge Drug (Drug)
结局指标
主要结局
Positive Subjective Drug Effects (i.e., Drug "Liking").
时间窗: Throughout study enrollment period (8-9 weeks)
The positive subjective effects of the most efficacious dose of the intravenous challenge drugs. These are measured using self-reported assessment by the participant in terms of drug "liking" rated on a visual analog scale of 0-100. Higher values indicate a greater drug effect.
次要结局
未报告次要终点
研究者
Sandra D. Comer
Research Scientist
New York State Psychiatric Institute