Aprepitant Effects on Oxycodone Response

Sharon Walsh9 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Enrollment

Conditions

Narcotic Abuse

Interventions

Aprepitant 0mgDRUG

Aprepitant 0mg, p.o. pretreatment

Aprepitant 40mgDRUG

Aprepitant 40mg, p.o. pretreatment

Aprepitant 200mgDRUG

Aprepitant 200mg, p.o. pretreatment

Oxycodone 0mg, p.o.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

University of Kentucky

Lexington, Kentucky, United States

Outcomes

Primary Outcomes

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.

Time frame: 42 days

Secondary Outcomes

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.

Time frame: 42 days

Data from ClinicalTrials.gov

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