MedPath

Aprepitant Effects on Oxycodone Response

Registration Number
NCT00999544
Lead Sponsor
Sharon Walsh
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
9
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Aprepitant 40 mg/ oxycodone 15 IN 0 POOxycodone 0mg, p.o.Aprepitant 40 mg/ oxycodone 15 IN 0 PO
Aprepitant 40 mg/ oxycodone 15 IN 0 POOxycodone 15mg, INAprepitant 40 mg/ oxycodone 15 IN 0 PO
Aprepitant 40 mg/ oxycodone 30 IN 0 POOxycodone 30mg, INAprepitant 40 mg/ oxycodone 30 IN 0 PO
Placebo aprepitant/ oxycodone 0 IN 40 POAprepitant 0mgPlacebo aprepitant/ oxycodone 0 IN 40 PO
Aprepitant 40 mg/ oxycodone 0 IN 40 POAprepitant 40mgAprepitant 40 mg/ oxycodone 0 IN 40 PO
Aprepitant 200 mg/ oxycodone 0 IN 0 POAprepitant 200mgAprepitant 200 mg/ oxycodone 0 IN 0 PO
Aprepitant 200 mg/ oxycodone 0 IN 20 POAprepitant 200mgAprepitant 200 mg/ oxycodone 0 IN 20 PO
Placebo aprepitant/ oxycodone 0 IN 20 POOxycodone 0mg, INPlacebo aprepitant/ oxycodone 0 IN 20 PO
Aprepitant 40 mg/ oxycodone 0 IN 20 POOxycodone 0mg, INAprepitant 40 mg/ oxycodone 0 IN 20 PO
Placebo aprepitant/ oxycodone 30 IN 0 POOxycodone 30mg, INPlacebo aprepitant/ oxycodone 30 IN 0 PO
Placebo aprepitant/0 mg oxycodone IN POAprepitant 0mgPlacebo aprepitant/Placebo oxycodone IN/PO
Placebo aprepitant/0 mg oxycodone IN POOxycodone 0mg, p.o.Placebo aprepitant/Placebo oxycodone IN/PO
Placebo aprepitant/0 mg oxycodone IN POOxycodone 0mg, INPlacebo aprepitant/Placebo oxycodone IN/PO
Placebo aprepitant/ oxycodone 15 IN 0 POAprepitant 0mgPlacebo aprepitant/ oxycodone 15 IN 0 PO
Placebo aprepitant/ oxycodone 15 IN 0 POOxycodone 0mg, p.o.Placebo aprepitant/ oxycodone 15 IN 0 PO
Placebo aprepitant/ oxycodone 15 IN 0 POOxycodone 15mg, INPlacebo aprepitant/ oxycodone 15 IN 0 PO
Placebo aprepitant/ oxycodone 30 IN 0 POAprepitant 0mgPlacebo aprepitant/ oxycodone 30 IN 0 PO
Placebo aprepitant/ oxycodone 30 IN 0 POOxycodone 0mg, p.o.Placebo aprepitant/ oxycodone 30 IN 0 PO
Aprepitant 40 mg/ oxycodone 0 IN 20 POOxycodone 20mg, p.o.Aprepitant 40 mg/ oxycodone 0 IN 20 PO
Placebo aprepitant/ oxycodone 0 IN 20 POAprepitant 0mgPlacebo aprepitant/ oxycodone 0 IN 20 PO
Placebo aprepitant/ oxycodone 0 IN 20 POOxycodone 20mg, p.o.Placebo aprepitant/ oxycodone 0 IN 20 PO
Placebo aprepitant/ oxycodone 0 IN 40 POOxycodone 40mg, p.o.Placebo aprepitant/ oxycodone 0 IN 40 PO
Placebo aprepitant/ oxycodone 0 IN 40 POOxycodone 0mg, INPlacebo aprepitant/ oxycodone 0 IN 40 PO
Aprepitant 40 mg/ oxycodone 0 IN 0 POAprepitant 40mgAprepitant 40 mg/ oxycodone 0 IN 0 PO
Aprepitant 40 mg/ oxycodone 0 IN 0 POOxycodone 0mg, p.o.Aprepitant 40 mg/ oxycodone 0 IN 0 PO
Aprepitant 40 mg/ oxycodone 0 IN 0 POOxycodone 0mg, INAprepitant 40 mg/ oxycodone 0 IN 0 PO
Aprepitant 40 mg/ oxycodone 0 IN 20 POAprepitant 40mgAprepitant 40 mg/ oxycodone 0 IN 20 PO
Aprepitant 40 mg/ oxycodone 0 IN 40 POOxycodone 0mg, INAprepitant 40 mg/ oxycodone 0 IN 40 PO
Aprepitant 40 mg/ oxycodone 15 IN 0 POAprepitant 40mgAprepitant 40 mg/ oxycodone 15 IN 0 PO
Aprepitant 40 mg/ oxycodone 0 IN 40 POOxycodone 40mg, p.o.Aprepitant 40 mg/ oxycodone 0 IN 40 PO
Aprepitant 40 mg/ oxycodone 30 IN 0 POAprepitant 40mgAprepitant 40 mg/ oxycodone 30 IN 0 PO
Aprepitant 40 mg/ oxycodone 30 IN 0 POOxycodone 0mg, p.o.Aprepitant 40 mg/ oxycodone 30 IN 0 PO
Aprepitant 200 mg/ oxycodone 0 IN 0 POOxycodone 0mg, p.o.Aprepitant 200 mg/ oxycodone 0 IN 0 PO
Aprepitant 200 mg/ oxycodone 0 IN 0 POOxycodone 0mg, INAprepitant 200 mg/ oxycodone 0 IN 0 PO
Aprepitant 200 mg/ oxycodone 0 IN 20 POOxycodone 20mg, p.o.Aprepitant 200 mg/ oxycodone 0 IN 20 PO
Aprepitant 200 mg/ oxycodone 0 IN 20 POOxycodone 0mg, INAprepitant 200 mg/ oxycodone 0 IN 20 PO
Aprepitant 200 mg/ oxycodone 0 IN 40 POAprepitant 200mgAprepitant 200 mg/ oxycodone 0 IN 40 PO
Aprepitant 200 mg/ oxycodone 15 IN 0 POOxycodone 15mg, INAprepitant 200 mg/ oxycodone 15 IN 0 PO
Aprepitant 200 mg/ oxycodone 30 IN 0 POAprepitant 200mgAprepitant 200 mg/ oxycodone 30 IN 0 PO
Aprepitant 200 mg/ oxycodone 30 IN 0 POOxycodone 0mg, p.o.Aprepitant 200 mg/ oxycodone 30 IN 0 PO
Aprepitant 200 mg/ oxycodone 0 IN 40 POOxycodone 40mg, p.o.Aprepitant 200 mg/ oxycodone 0 IN 40 PO
Aprepitant 200 mg/ oxycodone 0 IN 40 POOxycodone 0mg, INAprepitant 200 mg/ oxycodone 0 IN 40 PO
Aprepitant 200 mg/ oxycodone 15 IN 0 POAprepitant 200mgAprepitant 200 mg/ oxycodone 15 IN 0 PO
Aprepitant 200 mg/ oxycodone 15 IN 0 POOxycodone 0mg, p.o.Aprepitant 200 mg/ oxycodone 15 IN 0 PO
Aprepitant 200 mg/ oxycodone 30 IN 0 POOxycodone 30mg, INAprepitant 200 mg/ oxycodone 30 IN 0 PO
Primary Outcome Measures
NameTimeMethod
Abuse Liability Proxy42 days

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.

Secondary Outcome Measures
NameTimeMethod
Respiration Depression42 days

Respiration rate measured over 60 seconds. Data were collected across multiple time points, but the peak minimum score was used for this outcome measure.

Trial Locations

Locations (1)

University of Kentucky

🇺🇸

Lexington, Kentucky, United States

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