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Aprepitant Effects on Oxycodone Response

This study has been completed.
Sponsor:
Collaborators:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Sharon Walsh, University of Kentucky
ClinicalTrials.gov Identifier:
NCT00999544
First received: October 20, 2009
Last updated: July 19, 2013
Last verified: July 2013

October 20, 2009
July 19, 2013
October 2009
April 2011   (final data collection date for primary outcome measure)
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.
Opioid Abuse Liability [ Time Frame: 42 days ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00999544 on ClinicalTrials.gov Archive Site
Aprepitant Side Effects [ Time Frame: 42 days ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Aprepitant Effects on Oxycodone Response
New Neural Drug Targets: An Evaluation of the Effects of Aprepitant on the Response to Oxycodone

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.

Interventional
Not Provided
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Narcotic Abuse
  • Drug: Aprepitant
    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: Emend
  • Drug: Placebo
    placebo condition
    Other Name: Lactose
  • Drug: 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
Experimental: Aprepitant, Placebo, Oxycodone
This is a full crossover study in which all participants will receive every planned study drug condition.
Interventions:
  • Drug: Aprepitant
  • Drug: Placebo
  • Drug: Oxycodone
Walsh SL, Heilig M, Nuzzo PA, Henderson P, Lofwall MR. Effects of the NK1 antagonist, aprepitant, on response to oral and intranasal oxycodone in prescription opioid abusers. Addict Biol. 2013 Mar;18(2):332-43. doi: 10.1111/j.1369-1600.2011.00419.x. Epub 2012 Jan 19.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
9
April 2011
April 2011   (final data collection date for primary outcome measure)

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
Both
18 Years to 55 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00999544
09-0446, R01DA027031
No
Sharon Walsh, University of Kentucky
University of Kentucky
  • National Institute on Drug Abuse (NIDA)
  • Merck Sharp & Dohme Corp.
Principal Investigator: Sharon L Walsh, Ph.D. University of Kentucky
University of Kentucky
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP