Reducing the Abuse Liability of Prescription Opioids

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Reducing the Abuse Liability of Prescription Opioids

Conditions
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Addiction

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


Participation Criteria
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Eligibility Criteria
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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

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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opioid