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

NCT03389750 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 7565
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

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.

Conditions

Opioid Use Disorder

Outcome Measures

Primary Outcomes (1)

• Positive Subjective Drug Effects (i.e., Drug "Liking").

  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.

  Throughout study enrollment period (8-9 weeks)

Study Arms (4)

Intravenous Challenge Drug: Oxymorphone

ACTIVE COMPARATOR

Intravenous (IV) Dose Range: 1.8, 3.2, 5.6, 10 mg/70kg of the participant's body weight

Drug: Intravenous Challenge Drug

Intravenous Challenge Drug: Oxycodone

ACTIVE COMPARATOR

IV Dose Range: 10, 18, 32, 56 mg/70kg of the participant's body weight

Drug: Intravenous Challenge Drug

Intravenous Challenge Drug: Hydromorphone

ACTIVE COMPARATOR

IV Dose Range: 3.2, 5.6, 10, 18 mg/70kg of the participant's body weight

Drug: Intravenous Challenge Drug

Intravenous Challenge Drug: Placebo

PLACEBO COMPARATOR

IV saline

Drug: Intravenous Challenge Drug

Interventions

Intravenous Challenge Drug DRUG

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).

Also known as: Oxycodone, Oxymorphone, Hydromorphone, or Placebo

Intravenous Challenge Drug: Hydromorphone; Intravenous Challenge Drug: Oxycodone; Intravenous Challenge Drug: Oxymorphone; Intravenous Challenge Drug: Placebo

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• ≥ 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.

You may not qualify if:

• 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 1.
• 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.

Sponsors & Collaborators

• New York State Psychiatric Institute: lead
• University of Kentucky: collaborator

Study Sites (2)

University of Kentucky

Lexington, Kentucky, 40508, United States

Location

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

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

Oxycodone; Oxymorphone; Hydromorphone

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Codeine; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Jermaine Jones
• Organization: New York State Psychiatric Institute

jermaine.jones@nyspi.columbia.edu

646 774-6113

Study Officials

• Sandra D Comer, PhD

  New York State Psychiatric Institute / Columbia University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Scientist

Model Details: Intravenous Challenge Drug

Study Record Dates

• First Submitted: December 19, 2017
• First Posted: January 4, 2018
• Study Start: March 15, 2018
• Primary Completion: June 15, 2022
• Study Completion: June 28, 2023
• Last Updated: September 7, 2023
• Results First Posted: September 7, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)