Aprepitant Effects on Oxycodone Response

Study Overview
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Brief Summary
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Addressing the issue of opioid dependence and tolerance has public health implications for the treatment of opioid abuse (both heroin as well as pharmaceutical opioids) and for the treatment of pain. Recent preclinical data suggest a role for Substance P (NK-1) receptors in modulating both the acute and chronic response to opioids. The objective of this study is to determine whether pretreatment with aprepitant, a selective neurokinin-1 (NK-1) antagonist can reduce the direct response to an opioid agonist (oxycodone) on measures related to abuse liability and reinforcing effects.

Detailed Description
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Healthy adult volunteers with histories of illicit opioid use by the intranasal and oral routes will be admitted to this 6-week inpatient, crossover study. They will participate in 15 experimental test sessions, each lasting approximately 6.5 hours, during which they will receive a range of acute doses of aprepitant, including placebo, followed by challenge with oxycodone or placebo (given intranasally or orally). Multi-dimensional outcomes, including physiological (blood pressure, oxygen saturation, pupil diameter), subjective (questionnaires related to mood, abuse liability) and observer ratings will be collected repeatedly throughout each session. Data will be analyzed using parametric approaches to within-subject designs.

Official Title
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New Neural Drug Targets: An Evaluation of the Effects of Aprepitant on the Response to Oxycodone

Conditions
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Narcotic Abuse

Intervention / Treatment
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* Drug: Aprepitant 0mg
* Drug: Aprepitant 40mg
* Drug: Aprepitant 200mg
* Drug: Oxycodone 0mg, p.o.
* Drug: Oxycodone 20mg, p.o.
* Drug: Oxycodone 40mg, p.o.
* Drug: Oxycodone 0mg, IN
* Drug: Oxycodone 15mg, IN
* Drug: Oxycodone 30mg, IN


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recreational user of opioids Healthy Ages 18-55 years old Able to provide informed consent Exclusion Criteria: Ongoing medical or psychiatric condition that would be contraindicated for participation Past 30 day use of and P4503A4 inhibitor

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Within subject crossover designed that examined 15 experimental conditions within a single group of participants
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Placebo aprepitant/0 mg oxycodone IN PO<br>Placebo aprepitant/Placebo oxycodone IN/PO | Drug: Aprepitant 0mg<br>* Aprepitant 0mg, p.o. pretreatment<br>Drug: Oxycodone 0mg, p.o.<br>* Oxycodone 0mg, p.o.<br>Drug: Oxycodone 0mg, IN<br>* Oxycodone 0mg, IN<br>|
| Experimental: Placebo aprepitant/ oxycodone 15 IN 0 PO<br>Placebo aprepitant/ oxycodone 15 IN 0 PO | Drug: Aprepitant 0mg<br>* Aprepitant 0mg, p.o. pretreatment<br>Drug: Oxycodone 0mg, p.o.<br>* Oxycodone 0mg, p.o.<br>Drug: Oxycodone 15mg, IN<br>* Oxycodone 15mg, IN<br>|
| Experimental: Placebo aprepitant/ oxycodone 30 IN 0 PO<br>Placebo aprepitant/ oxycodone 30 IN 0 PO | Drug: Aprepitant 0mg<br>* Aprepitant 0mg, p.o. pretreatment<br>Drug: Oxycodone 0mg, p.o.<br>* Oxycodone 0mg, p.o.<br>Drug: Oxycodone 30mg, IN<br>* Oxycodone 30mg, IN<br>|
| Experimental: Placebo aprepitant/ oxycodone 0 IN 20 PO<br>Placebo aprepitant/ oxycodone 0 IN 20 PO | Drug: Aprepitant 0mg<br>* Aprepitant 0mg, p.o. pretreatment<br>Drug: Oxycodone 20mg, p.o.<br>* Oxycodone 20mg, p.o.<br>Drug: Oxycodone 0mg, IN<br>* Oxycodone 0mg, IN<br>|
| Experimental: Placebo aprepitant/ oxycodone 0 IN 40 PO<br>Placebo aprepitant/ oxycodone 0 IN 40 PO | Drug: Aprepitant 0mg<br>* Aprepitant 0mg, p.o. pretreatment<br>Drug: Oxycodone 40mg, p.o.<br>* Oxycodone 40mg, p.o.<br>Drug: Oxycodone 0mg, IN<br>* Oxycodone 0mg, IN<br>|
| Experimental: Aprepitant 40 mg/ oxycodone 0 IN 0 PO<br>Aprepitant 40 mg/ oxycodone 0 IN 0 PO | Drug: Aprepitant 40mg<br>* Aprepitant 40mg, p.o. pretreatment<br>Drug: Oxycodone 0mg, p.o.<br>* Oxycodone 0mg, p.o.<br>Drug: Oxycodone 0mg, IN<br>* Oxycodone 0mg, IN<br>|
| Experimental: Aprepitant 40 mg/ oxycodone 0 IN 20 PO<br>Aprepitant 40 mg/ oxycodone 0 IN 20 PO | Drug: Aprepitant 40mg<br>* Aprepitant 40mg, p.o. pretreatment<br>Drug: Oxycodone 20mg, p.o.<br>* Oxycodone 20mg, p.o.<br>Drug: Oxycodone 0mg, IN<br>* Oxycodone 0mg, IN<br>|
| Experimental: Aprepitant 40 mg/ oxycodone 0 IN 40 PO<br>Aprepitant 40 mg/ oxycodone 0 IN 40 PO | Drug: Aprepitant 40mg<br>* Aprepitant 40mg, p.o. pretreatment<br>Drug: Oxycodone 40mg, p.o.<br>* Oxycodone 40mg, p.o.<br>Drug: Oxycodone 0mg, IN<br>* Oxycodone 0mg, IN<br>|
| Experimental: Aprepitant 40 mg/ oxycodone 15 IN 0 PO<br>Aprepitant 40 mg/ oxycodone 15 IN 0 PO | Drug: Aprepitant 40mg<br>* Aprepitant 40mg, p.o. pretreatment<br>Drug: Oxycodone 0mg, p.o.<br>* Oxycodone 0mg, p.o.<br>Drug: Oxycodone 15mg, IN<br>* Oxycodone 15mg, IN<br>|
| Experimental: Aprepitant 40 mg/ oxycodone 30 IN 0 PO<br>Aprepitant 40 mg/ oxycodone 30 IN 0 PO | Drug: Aprepitant 40mg<br>* Aprepitant 40mg, p.o. pretreatment<br>Drug: Oxycodone 0mg, p.o.<br>* Oxycodone 0mg, p.o.<br>Drug: Oxycodone 30mg, IN<br>* Oxycodone 30mg, IN<br>|
| Experimental: Aprepitant 200 mg/ oxycodone 0 IN 0 PO<br>Aprepitant 200 mg/ oxycodone 0 IN 0 PO | Drug: Aprepitant 200mg<br>* Aprepitant 200mg, p.o. pretreatment<br>Drug: Oxycodone 0mg, p.o.<br>* Oxycodone 0mg, p.o.<br>Drug: Oxycodone 0mg, IN<br>* Oxycodone 0mg, IN<br>|
| Experimental: Aprepitant 200 mg/ oxycodone 0 IN 20 PO<br>Aprepitant 200 mg/ oxycodone 0 IN 20 PO | Drug: Aprepitant 200mg<br>* Aprepitant 200mg, p.o. pretreatment<br>Drug: Oxycodone 20mg, p.o.<br>* Oxycodone 20mg, p.o.<br>Drug: Oxycodone 0mg, IN<br>* Oxycodone 0mg, IN<br>|
| Experimental: Aprepitant 200 mg/ oxycodone 0 IN 40 PO<br>Aprepitant 200 mg/ oxycodone 0 IN 40 PO | Drug: Aprepitant 200mg<br>* Aprepitant 200mg, p.o. pretreatment<br>Drug: Oxycodone 40mg, p.o.<br>* Oxycodone 40mg, p.o.<br>Drug: Oxycodone 0mg, IN<br>* Oxycodone 0mg, IN<br>|
| Experimental: Aprepitant 200 mg/ oxycodone 15 IN 0 PO<br>Aprepitant 200 mg/ oxycodone 15 IN 0 PO | Drug: Aprepitant 200mg<br>* Aprepitant 200mg, p.o. pretreatment<br>Drug: Oxycodone 0mg, p.o.<br>* Oxycodone 0mg, p.o.<br>Drug: Oxycodone 15mg, IN<br>* Oxycodone 15mg, IN<br>|
| Experimental: Aprepitant 200 mg/ oxycodone 30 IN 0 PO<br>Aprepitant 200 mg/ oxycodone 30 IN 0 PO | Drug: Aprepitant 200mg<br>* Aprepitant 200mg, p.o. pretreatment<br>Drug: Oxycodone 0mg, p.o.<br>* Oxycodone 0mg, p.o.<br>Drug: Oxycodone 30mg, IN<br>* Oxycodone 30mg, IN<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Abuse Liability Proxy | Visual analog scale ratings (from 0-100) on the subject-rated measure of How much do you like the drug? with higher scores indicating greater abuse liability (and 100 anchored with extremely and zero indicating none anchored with none at all. Data were collected across multiple time points but the peak maximum score was used for the primary outcome measure. | 42 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Respiration Depression | Respiration rate measured over 60 seconds. Data were collected across multiple time points, but the peak minimum score was used for this outcome measure. | 42 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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opioid, oxycodone, NK1 antagonist, aprepitant, intranasal, abuse