Reducing the Abuse of Opioids in Drug Users

Reducing the Abuse Liability of Prescription Opioids in Recreational Drug Users: A Pilot Study

The consequences of prescription opioid abuse are serious and the number of deaths from unintended overdose have quadrupled over the last 15+ years. Opioid analgesics remain among the most commonly abused class of substances in the United States. Moreover, patients who take pain medications for legitimate reasons may develop an opioid use disorder (OUD), with as many as 1 in 4 patients becoming dependent on their pain medications. Because of changing access to prescription opioid analgesics due to an increasingly negative prescribing climate and changes in guidelines, patients often turn to heroin, with an estimated 1 in 15 pain patients trying heroin within 10 years. Pain is a symptom that can be severely debilitating and needs to be treated adequately to improve the quality of life. Clinicians, then, are in a proverbial "catch-22" situation whereby treating a patient's chronic pain also exposes them to medications with substantial abuse liability and overdose risk. In this proposal, a method aimed at reducing the abuse potential of prescription opioid medications, without altering their analgesic efficacy, is described.

The study team hypothesize that this can be accomplished by administering a fixed-dose-combination of an opioid with an atypical antipsychotic drug, in the same pill or capsule.

Study Overview

• Status: Terminated
• Conditions: Opioid Dependence; Opioid Abuse, Unspecified
• Intervention / Treatment: Drug: Oxycodone/Placebo; Drug: Oxycodone/Risperidone; Drug: Oxycodone/Ziprasidone

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78229
      • Westgate Pain Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients between 21 to 65 years of age, capable of understanding and providing consent in English, and capable of complying with the outcome instruments used.
• Recreational opioid use (i.e. defined as prescription opioid use for nontherapeutic purposes on at least 10 occasions within the previous year and at least once in the 12 weeks prior to screening)
• Reported tolerated doses to opioid medications

Exclusion Criteria:

• Currently receiving pharmacotherapy for psychiatric disorder, current suicide risk, or past history of major psychiatric disorder such as bipolar disorder/psychosis
• Presence of dementia
• Current neuroleptic medication in past 30 days
• Pregnancy
• Positive drug urine test for Barbiturates, Benzodiazepines, Methadone, and Buprenorphine.
• Subjects with a prolonged QT interval greater than 430ms (i.e. QTc >430ms)
• Subjects with a heart rate of less than 60 or greater than 100bpm will be assessed by a physician for symptomatic bradycardia/tachycardia and eligibility determined on a case-by-case basis
• Subjects with serum potassium and/or magnesium outside of normal range of our institutional laboratory within the past three months from time of screening.
• Subjects who appears intoxicated on the day of study visit by an on-site physician.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Oxycodone/Placebo; Each study participant will receive all three study interventions in random order.In this arm, the participant receives oxycodone or placebo	Drug: Oxycodone/Placebo; Oxycodone 20 mg plus placebo; Other Names: Oxycontin/Placebo
Active Comparator: Oxycodone/Risperidone; Each study participant will receive all three study interventions in random order. In this arm the participant receives a combination of oxycodone or risperidone	Drug: Oxycodone/Risperidone; Oxycodone (20mg) plus Risperidone (2 mg); Other Names: Oxycontin/Risperdal
Active Comparator: Oxycodone/Ziprasidone; Each study participant will receive all three study interventions in random order. In this arm the participant receives a combination of oxycodone or ziprasidone	Drug: Oxycodone/Ziprasidone; Oxycodone (20mg) plus Ziprasidone (80 mg); Other Names: Oxycontin/Geodon

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Bipolar Visual Analog Scale (VAS) of Drug Likability	The bipolar VAS is used to measure the Change in magnitude of "drug liking". The Drug Effects Questionnaire AKA the bipolar VAS of Drug Likability is a 5 item self-administered assessment where participants place a mark on a line from 0 to 100, "strongly dislike" at 0 (on the left hand side), "no effect" at 50 (in the center) and "strongly like" at 100 (on the far right). Change from visit 2 to visit 6 will be measured.	Study visit 2 to study visit 6, an average of 10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Profile of Mood States (POMS)	POMS is a self-administered, standard validated psychological test formulated by McNair et al. (1971). It is a used to assess transient, distinct mood states. The questionnaire contains 65 words/statements that describe feelings people have. Outcome will be assessed using categorical and continuous data analysis comparing across groups. Change from visit 2 to visit 6 will be measured.	Study visit 2 to study visit 6, an average of 10 days
Change in Addiction Research Center Inventory Short Form (ARCI-SF)	The ARCI is a self-administered, standardized questionnaire for assessing subjective effects of psychoactive drugs that was developed in the early 1960s at the National Institute of Mental Health Addiction Research Center. For this study, we will be using the 49-item short form. Outcome will be assessed using categorical and continuous data analysis comparing across groups. Change from visit 2 to visit 6 will be measured.	Study visit 2 to study visit 6, an average of 10 days

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center at San Antonio
• Investigators: Principal Investigator: Ameet Nagpal, MD, UT Health San Antonio

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Actual): March 23, 2021
• Study Completion (Actual): January 21, 2022

Study Registration Dates

• First Submitted: February 5, 2019
• First Submitted That Met QC Criteria: February 8, 2019
• First Posted (Actual): February 12, 2019

Study Record Updates

• Last Update Posted (Actual): February 15, 2022
• Last Update Submitted That Met QC Criteria: January 31, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Narcotic-Related Disorders; Opioid-Related Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Dopamine Agents; Serotonin Antagonists; Dopamine Antagonists; Risperidone; Ziprasidone; Oxycodone
• Other Study ID Numbers: HSC20180167

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No