A Study to Evaluate the Abuse Potential of Oxymorphone Compared to Other Mu Opioid Agonists.

• ClinicalTrials.gov Identifier: NCT03389750
• Recruitment Status: Recruiting
• First Posted: January 4, 2018
• Last Update Posted: June 29, 2021
• Sponsor: New York State Psychiatric Institute
• Collaborator: University of Kentucky
• Information provided by (Responsible Party): Sandra D. Comer, New York State Psychiatric Institute

Study Description

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, morphine, and hydromorphone) among physically dependent opioid abusers. This inpatient study examines the reinforcing effects of oxymorphone and other mu opioid agonists using drug self-administration procedures, and assessments of subjective effects.

Condition or disease	Intervention/treatment	Phase
Opioid-use Disorder; Opioid Abuse	Drug: Intravenous Challege Drug	Phase 2

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, morphine, and hydromorphone). A total of 20 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 the 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 on 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 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Intravenous Challenge Drug
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Basic Science
• 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
• Actual Study Start Date: March 15, 2018
• Estimated Primary Completion Date: May 2022
• Estimated Study Completion Date: December 2022

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Intravenous Challege Drug: Oxymorphone; Intravenous (IV) Dose Range: 0, 18, 32, 56 mg/70kg of the participant's body weight	Drug: Intravenous Challege Drug; Intravenous administration of opioid drugs (oxycodone, oxymorphone, morphine, hydromorphone), for the purpose of comparison of their abuse potential among each other, and in comparison to placebo (saline).; Other Name: Oxycodone, Oxymorphone, Morphine, Hydromorphone, or Placebo
Active Comparator: Intravenous Challege Drug: Oxycodone; IV Dose Range: 0, 18, 32, 56 mg/70kg of the participant's body weight	Drug: Intravenous Challege Drug; Intravenous administration of opioid drugs (oxycodone, oxymorphone, morphine, hydromorphone), for the purpose of comparison of their abuse potential among each other, and in comparison to placebo (saline).; Other Name: Oxycodone, Oxymorphone, Morphine, Hydromorphone, or Placebo
Active Comparator: Intravenous Challege Drug: Morphine; IV Dose Range: 0, 18, 32, 56 mg/70kg of the participant's body weight	Drug: Intravenous Challege Drug; Intravenous administration of opioid drugs (oxycodone, oxymorphone, morphine, hydromorphone), for the purpose of comparison of their abuse potential among each other, and in comparison to placebo (saline).; Other Name: Oxycodone, Oxymorphone, Morphine, Hydromorphone, or Placebo
Active Comparator: Intravenous Challege Drug: Hydromorphone; IV Dose Range: 0, 5.6, 10, 18 mg/70kg of the participant's body weight	Drug: Intravenous Challege Drug; Intravenous administration of opioid drugs (oxycodone, oxymorphone, morphine, hydromorphone), for the purpose of comparison of their abuse potential among each other, and in comparison to placebo (saline).; Other Name: Oxycodone, Oxymorphone, Morphine, Hydromorphone, or Placebo
Placebo Comparator: Intravenous Challege Drug: Placebo; IV saline	Drug: Intravenous Challege Drug; Intravenous administration of opioid drugs (oxycodone, oxymorphone, morphine, hydromorphone), for the purpose of comparison of their abuse potential among each other, and in comparison to placebo (saline).; Other Name: Oxycodone, Oxymorphone, Morphine, Hydromorphone, or Placebo

Outcome Measures

Primary Outcome Measures :

1. Reinforcing effects [ Time Frame: Through study completion (8-9 weeks) ]
   Reinforcing effects of the most efficacious dose of each of the intravenous challenge drug as assessed by percent drug (vs money) choices.

Secondary Outcome Measures :

1. Positive Subjective Effects [ Time Frame: Through study completion (8-9 weeks) ]
   The positive subjective effects of the most efficacious dose of each of the intravenous challenge drugs. These are measures using self-reported assessment by the participant in terms of drug "liking," or "good effect," rated on a visual analog scale of 0-100.

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Jermaine D Jones, PhD; 646 774-6113; jermaine.jones@nyspi.columbia.edu

Contact: Vincent Woolfolk, MA; 646 774-8023; vincent.woolfolk@nyspi.columbia.edu

Locations

United States, Kentucky

University of Kentucky; Not yet recruiting

Lexington, Kentucky, United States, 40508

Contact: Shanna Babalonis, PhD 859-257-1881 babalonis@uky.edu

Contact: Paul Nuzzo, MS (859) 257-1881 pnuzz2@uky.edu

Principal Investigator: Sharon L Walsh, PhD

United States, New York

New York State Psychiatric Institute in the Division on Substance Use Disorders; Recruiting

New York, New York, United States, 10032

Contact: Vincent Woolfolk, MA 646-774-8032 Vincent.woolfolk@nyspi.columbia.edu

Contact: Ben Foote, BA 646 774-6243 Ben.foote@nyspi.columbia.edu

Principal Investigator: Sandra D Comer, PhD

Sub-Investigator: Jermaine D Jones, PhD

Sub-Investigator: Jeanne M Manubay, MD

Sponsors and Collaborators

New York State Psychiatric Institute

University of Kentucky

Investigators

• Principal Investigator: Sandra D Comer, PhD; New York State Psychiatric Institute / Columbia University Medical Center

More Information

• Responsible Party: Sandra D. Comer, Research Scientist, New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT03389750
• Other Study ID Numbers: 7565
• First Posted: January 4, 2018
• Last Update Posted: June 29, 2021
• Last Verified: June 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Opioid-Related Disorders; Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Oxymorphone; Morphine; Oxycodone; Hydromorphone; Analgesics, Opioid; Narcotics; Central Nervous System Depressants; Physiological Effects of Drugs; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Adjuvants, Anesthesia