A Study to Evaluate the Abuse Potential of Oxymorphone Compared to Other Mu Opioid Agonists.
Condition: Opioid Use Disorder
MeSH terms: Opioid-Related Disorders
Intervention: Intravenous Challenge Drug
Intervention description: Intravenous administration of opioid drugs (oxycodone, oxymorphone, hydromorphone), for the purpose of comparison of their abuse potential among each other, and in comparison to placebo (saline).
Intervention MeSH terms: Oxymorphone; Oxycodone; Hydromorphone
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Intravenous Challenge Drug
Masking: Double (Participant, Outcomes Assessor)
Enrollment: 16.0
Sex: All
Minimum age: 21 Years
Maximum age: 55 Years
Healthy volunteers: No

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.
    

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.