Aprepitant Effects on Oxycodone Response
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.
|Study Design:||Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
|Official Title:||New Neural Drug Targets: An Evaluation of the Effects of Aprepitant on the Response to Oxycodone|
- Abuse Liability Proxy [ Time Frame: 42 days ] [ Designated as safety issue: No ]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.
- Aprepitant Side Effects [ Time Frame: 42 days ] [ Designated as safety issue: No ]
|Study Start Date:||October 2009|
|Study Completion Date:||April 2011|
|Primary Completion Date:||April 2011 (Final data collection date for primary outcome measure)|
Experimental: Aprepitant, Placebo, Oxycodone
This is a full crossover study in which all participants will receive every planned study drug condition.
Aprepitant (0, 40, 200 mg, p.o.) to be given in combination with a range of oxycodone doses (p.o. 20 and 40 mg, i.n. 15 and 30 mg) and double-dummy placebo with each aprepitant and oxycodone being tested once in each subject (a total of 15 conditions) in random order
Other Name: EmendDrug: Placebo
Other Name: LactoseDrug: Oxycodone
Oxycodone was administered at 15 and 30 mg intranasally and at 20 and 40 mg orally once after each of the oral pretreatment conditions (placebo and active aprepitant)
Other Name: Roxicet
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.
|United States, Kentucky|
|University of Kentucky|
|Lexington, Kentucky, United States, 40502|
|Principal Investigator:||Sharon L Walsh, Ph.D.||University of Kentucky|