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
  Purpose

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.


Condition Intervention
Narcotic Abuse
Drug: Aprepitant
Drug: Placebo
Drug: Oxycodone

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University of Kentucky:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • Aprepitant Side Effects [ Time Frame: 42 days ] [ Designated as safety issue: No ]

Enrollment: 9
Study Start Date: October 2009
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Aprepitant, Placebo, Oxycodone
This is a full crossover study in which all participants will receive every planned study drug condition.
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00999544

Locations
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40502
Sponsors and Collaborators
University of Kentucky
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Sharon L Walsh, Ph.D. University of Kentucky
  More Information

Publications:
Responsible Party: Sharon Walsh, Director Center on Drug and Alcohol Research, University of Kentucky
ClinicalTrials.gov Identifier: NCT00999544     History of Changes
Other Study ID Numbers: 09-0446, R01DA027031
Study First Received: October 20, 2009
Results First Received: November 13, 2012
Last Updated: July 19, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Kentucky:
opioid
oxycodone
NK1 antagonist
aprepitant
intranasal
abuse

Additional relevant MeSH terms:
Opioid-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Oxycodone
Aprepitant
Fosaprepitant
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Antiemetics
Autonomic Agents
Gastrointestinal Agents
Neurokinin-1 Receptor Antagonists
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 11, 2014