Reducing the Abuse of Opioids in Drug Users

Study Overview
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Brief Summary
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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.

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

Conditions
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Opioid Abuse, Unspecified, Opioid Dependence

Intervention / Treatment
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* Drug: Oxycodone/Placebo
* Drug: Oxycodone/Risperidone
* Drug: Oxycodone/Ziprasidone


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Double-blinded, crossover study
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Oxycodone/Placebo<br>Each study participant will receive all three study interventions in random order.In this arm, the participant receives oxycodone or placebo | Drug: Oxycodone/Placebo<br>* Oxycodone 20 mg plus placebo<br>* Other names: Oxycontin/Placebo;|
| Active Comparator: Oxycodone/Risperidone<br>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<br>* Oxycodone (20mg) plus Risperidone (2 mg)<br>* Other names: Oxycontin/Risperdal;|
| Active Comparator: Oxycodone/Ziprasidone<br>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<br>* Oxycodone (20mg) plus Ziprasidone (80 mg)<br>* Other names: Oxycontin/Geodon;|

What is the study measuring?
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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 |