Aprepitant Effects on Oxycodone Response

Narcotic Abuse Clinical Trial

Official title:

New Neural Drug Targets: An Evaluation of the Effects of Aprepitant on the Response to Oxycodone

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00999544
• Other study ID #: 09-0446
• Secondary ID: R01DA027031
• Status: Completed
• Phase: N/A
• First received: October 20, 2009
• Last updated: July 19, 2013
• Start date: October 2009
• Est. completion date: April 2011

Study information

• Verified date: July 2013
• Source: University of Kentucky
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: April 2011
• Est. primary completion date: April 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Narcotic Abuse

Intervention

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
• Placebo
placebo condition
• 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)

Locations

Country	Name	City	State
United States	University of Kentucky	Lexington	Kentucky

Sponsors (3)

Lead Sponsor	Collaborator
University of Kentucky	Merck Sharp & Dohme Corp., National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	42 days	No
Secondary	Aprepitant Side Effects		42 days	No