Clinical trial NCT03389750: A Study to Evaluate the Abuse Potential of Oxymorphone Compared to Other Mu Opioid Agonists.
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Opioid Use Disorder
Lead sponsor: New York State Psychiatric Institute
Sponsor class: OTHER
Collaborators: name: University of Kentucky
First posted: 2018-01-04
Enrollment: 16
Sex: ALL
Minimum age (years): 21
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Intravenous Challenge Drug
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Able to understand and provide signed and dated written consent.
2. 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.
3. 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).
4. ≥ 21 and ≤ 55 years of age.
5. Body mass index (BMI) ≥ 18 and ≤ 35 kg/m2 and weight ≥ 50 kg (110 pounds).
6. Otherwise healthy as determined by the investigator.
7. Demonstrate understanding how to complete the self-administration tasks and VAS Questionnaire.
8. Women of childbearing potential must not be pregnant or breastfeeding at screening.
9. Willing and able to comply with all testing requirements defined in the protocol.

participation in the Study Treatment Phase:

1. 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.
2. 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.
3. 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.

Exclusion Criteria:

1. History of a medical or psychiatric disorder that would prevent successful completion of the study.
2. Current DSM-5 diagnosis of substance use disorders requiring medical management other than OUD.
3. 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).
4. Currently seeking or participating in treatment for substance use disorder.
5. Physically dependent on drugs of abuse (other than opioids, nicotine, or caffeine) or alcohol.
6. Medically important deviation from normal limits on physical examination, vital signs, screening laboratory tests, or 12--lead ECG.
7. Significant cardiovascular, hepatic, renal, respiratory, gastrointestinal, endocrine, immunologic, dermatologic, hematologic, or neurologic disorder.
8. Any surgical, or medical condition that may interfere with the absorption, distribution, metabolism, or excretion of the test drug.
9. Family history of long QT syndrome and/or unexpected sudden cardiac death or is known to have QTc \> 500 ms at screening.
10. 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.
11. Hypersensitivity to opioids or any drug intended for use in this study.
12. Acute gastrointestinal symptoms (e.g., nausea, vomiting, fever, or Diarrhea unrelated to opioid withdrawal) ≤ 7 days before Day 1.
13. Any of the following values for laboratory tests at Screening:

    1. A positive pregnancy test in women of childbearing potential.
    2. Hemoglobin \< 11 g/dL in males and \< 10 gm/dL in females.
    3. Neutrophil count \< 1.0 × 109/L.
    4. Platelet count \< 75 × 109/L.
    5. Creatinine clearance \< 50 ml/min per modified Cockcroft-Gault equation.
    6. Aspartate aminotransferase or alanine aminotransferase \> 3.0x upper limit of normal.

Primary outcomes:
measure: Positive Subjective Drug Effects (i.e., Drug "Liking").
timeFrame: Throughout study enrollment period (8-9 weeks)
Secondary outcomes:
Other outcomes:
Locations:
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: New York
country: United States
facility: New York State Psychiatric Institute in the Division on Substance Use Disorders
state: New York
Study officials:
affiliation: New York State Psychiatric Institute / Columbia University Medical Center
name: Sandra D Comer, PhD
role: PRINCIPAL_INVESTIGATOR
References: