Reducing the Abuse Liability of Prescription Opioids

Opioid (commonly called narcotic) pain medicines are, after marijuana, the most commonly abused substances in the United States. Patients who take opioids for legitimate reasons may become addicted; for example, as many as 1 in 4 patients meet the criteria for current opioid dependence. It is very important that a way is found to provide pain relief while minimizing the addiction potential of these widely used pain medications.

The study aim to find out if the use of another type of medication given in addition to an opioid will reduce the addiction potential of the opioid.

The study is trying to find out if the ability of the opioid to relieve pain is changed when given with the other medication, and to see if the euphoric sensation or "liking" of the opioid pain medication is reduced when taken with the other medication.

Study Overview

• Status: Completed
• Conditions: Addiction
• Intervention / Treatment: Drug: Oxycodone; Drug: Risperidone; Drug: Ziprasidone

Detailed Description

This study involves the use of an investigational combination of drugs. "Oxycodone with Risperidone" and "Oxycodone with Ziprasidone" are called "Investigational" because the U.S. Food & Drug Administration (FDA) has not approved these drug combinations for the purpose of this study. Individually, each of these drugs is approved by the FDA for other reasons (i.e. oxycodone as a painkiller, while risperidone and ziprasidone are approved as anti-psychotic medications), but the administration of these drugs together has not been studied before or been approved by the FDA for this purpose.

This is the first study involving humans to examine the safety of this combination of drugs and how they work together. The goal of the study is to find out what effects, good and/or bad, it has on people who take them. Because the combination has not been studied in humans before, information about the safety and effectiveness is incomplete and all of the side effects are not yet known.

• Study Type: Interventional
• Enrollment (Actual): 15
• 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:

• Requirement of prior exposure to opioids

Exclusion Criteria:

• Presence of psychiatric comorbidity
• Presence of chronic pain disorder
• Presence or history of substance use disorder
• Current analgesic or neuroleptic medication usage (any medication for pain, including over-the-counter analgesics like ibuprofen/acetaminophen)
• Pregnancy
• Positive drug urine test
• Continuous opioid misuse measure score of < 9
• Presence or history of diabetes
• Presence or history of cardiac disease or arrhythmia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Oxycodone; This arm will be considered the control arm, containing oxycodone as the placebo.	Drug: Oxycodone; Oxycodone alone in a capsule will be considered the control. Oxycodone 15 mg will also be used in combination with other study drugs; Other Names: Oxycontin
Experimental: Oxycodone and Risperidone; Administration of oxycodone plus risperidone in a single capsule	Drug: Oxycodone; Oxycodone alone in a capsule will be considered the control. Oxycodone 15 mg will also be used in combination with other study drugs; Other Names: Oxycontin; Drug: Risperidone; Risperidone 1mg to be used in combination with other drugs; Other Names: Risperdal
Experimental: Oxycodone and Ziprasidone; Administration of oxycodone and risperidone in a single capsule	Drug: Oxycodone; Oxycodone alone in a capsule will be considered the control. Oxycodone 15 mg will also be used in combination with other study drugs; Other Names: Oxycontin; Drug: Ziprasidone; Ziprasidone 80mg to be used in combination with other study drugs; Other Names: Geodon

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of analgesic efficacy- Cold pressor	Perform quantitative evaluations of the analgesic efficacy of a novel fixed dose combination (FDC) of an opioid (oxycodone) in combination with one of two atypical antipsychotic drugs (either risperidone or ziprasidone) compared to the opioid alone. Analgesic efficacy will be measured with the cold pressor task which measures thermal pain. The cold pressor task measures the time the participant can tolerate their hand being submerged in the cold water up to a maximum of 5 minutes.	two weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of analgesic efficacy- Thumb pressor	Perform quantitative evaluations of the analgesic efficacy of a novel fixed dose combination (FDC) of an opioid (oxycodone) in combination with one of two atypical antipsychotic drugs (either risperidone or ziprasidone) compared to the opioid alone. Analgesic efficacy will be measured with the thumb pressor task which measures mechanical pain. The thumb pressor task measures the amount of weight they can tolerate on the nail of their thumb up to a maximum of 10 kg.	two weeks
Drug liking	Examine subjective ratings of drug liking of the FDC compared to that of the opioid alone using the Bipolar Visual analog scale on a scale of 0-Dislike to 100-Extremely like.	two weeks
Addiction Research Center Inventory test questionnaire	Perform the Addiction Research Center Inventory Short Form (ARCI-SF) questionnaire to assess the drug-induced transient alterations in distinct mood states of the FDC compared to those of the opioid alone. 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, the study team will be using the 49-item short form. Outcome will be assessed using categorical and continuous data analysis comparing across groups. The ARCI-SF measures the subjective effects of a variety of drugs such as alcohol, morphine, LSD, and pentobarbital by a score for each subset. The higher a participant scores on a subset, the more similar the effects of the drug are to the known drug such as alcohol.	two weeks
Profile of Mood States test questionnaire	Perform a subset of the Profile of Mood States questionnaire to assess drug-induced transient alterations in distinct mood states following administration of the FDC compared to those of the opioid alone. 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. The POMS is a non-diagnostic test that assesses transient and distinct mood states such as tension, depression, anger, fatigue, confusion, vigor, and total mood disturbance. The higher a participant scores in each group, the more they experience that mood state.	two weeks

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center at San Antonio
• Investigators: Principal Investigator: Max Eckmann, MD, University of Texas Health at San Antonio

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2017
• Primary Completion (Actual): June 1, 2019
• Study Completion (Actual): January 1, 2020

Study Registration Dates

• First Submitted: August 19, 2020
• First Submitted That Met QC Criteria: October 13, 2020
• First Posted (Actual): October 14, 2020

Study Record Updates

• Last Update Posted (Actual): October 14, 2020
• Last Update Submitted That Met QC Criteria: October 13, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: opioid
• Additional Relevant MeSH Terms: Compulsive Behavior; Impulsive Behavior; Behavior, Addictive; 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: HSC20170141H

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Individual participant data will be shared with other collaborating investigators, and unidentified data will be shared at study completion as a publication.
• IPD Sharing Time Frame: At study completion.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No