Aprepitant Effects on Oxycodone Response

Sharon Walsh

Status: Completed

Conditions: Narcotic Abuse

Treatments: Drug: Oxycodone 30mg, IN; Drug: Oxycodone 20mg, p.o.; Drug: Aprepitant 40mg; Drug: Aprepitant 200mg; Drug: Oxycodone 15mg, IN; Drug: Oxycodone 0mg, IN; Drug: Oxycodone 0mg, p.o.; Drug: Aprepitant 0mg; Drug: Oxycodone 40mg, p.o.

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT00999544

R01DA027031 (U.S. NIH Grant/Contract)

09-0446

Details and patient eligibility

About

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.

Full 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.

Enrollment: 9 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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9 participants in 15 patient groups

Placebo aprepitant/0 mg oxycodone IN PO

Experimental group

Description:

Placebo aprepitant/Placebo oxycodone IN/PO

Treatment:

Drug: Oxycodone 0mg, p.o.

Drug: Aprepitant 0mg

Drug: Oxycodone 0mg, IN

Placebo aprepitant/ oxycodone 15 IN 0 PO

Experimental group

Description:

Placebo aprepitant/ oxycodone 15 IN 0 PO

Treatment:

Drug: Oxycodone 0mg, p.o.

Drug: Aprepitant 0mg

Drug: Oxycodone 15mg, IN

Placebo aprepitant/ oxycodone 30 IN 0 PO

Experimental group

Description:

Placebo aprepitant/ oxycodone 30 IN 0 PO

Treatment:

Drug: Oxycodone 0mg, p.o.

Drug: Aprepitant 0mg

Drug: Oxycodone 30mg, IN

Placebo aprepitant/ oxycodone 0 IN 20 PO

Experimental group

Description:

Placebo aprepitant/ oxycodone 0 IN 20 PO

Treatment:

Drug: Aprepitant 0mg

Drug: Oxycodone 0mg, IN

Drug: Oxycodone 20mg, p.o.

Placebo aprepitant/ oxycodone 0 IN 40 PO

Experimental group

Description:

Placebo aprepitant/ oxycodone 0 IN 40 PO

Treatment:

Drug: Aprepitant 0mg

Drug: Oxycodone 0mg, IN

Drug: Oxycodone 40mg, p.o.

Aprepitant 40 mg/ oxycodone 0 IN 0 PO

Experimental group

Description:

Aprepitant 40 mg/ oxycodone 0 IN 0 PO

Treatment:

Drug: Oxycodone 0mg, p.o.

Drug: Oxycodone 0mg, IN

Drug: Aprepitant 40mg

Aprepitant 40 mg/ oxycodone 0 IN 20 PO

Experimental group

Description:

Aprepitant 40 mg/ oxycodone 0 IN 20 PO

Treatment:

Drug: Oxycodone 0mg, IN

Drug: Oxycodone 20mg, p.o.

Drug: Aprepitant 40mg

Aprepitant 40 mg/ oxycodone 0 IN 40 PO

Experimental group

Description:

Aprepitant 40 mg/ oxycodone 0 IN 40 PO

Treatment:

Drug: Oxycodone 0mg, IN

Drug: Aprepitant 40mg

Drug: Oxycodone 40mg, p.o.

Aprepitant 40 mg/ oxycodone 15 IN 0 PO

Experimental group

Description:

Aprepitant 40 mg/ oxycodone 15 IN 0 PO

Treatment:

Drug: Oxycodone 0mg, p.o.

Drug: Aprepitant 40mg

Drug: Oxycodone 15mg, IN

Aprepitant 40 mg/ oxycodone 30 IN 0 PO

Experimental group

Description:

Aprepitant 40 mg/ oxycodone 30 IN 0 PO

Treatment:

Drug: Oxycodone 0mg, p.o.

Drug: Aprepitant 40mg

Drug: Oxycodone 30mg, IN

Aprepitant 200 mg/ oxycodone 0 IN 0 PO

Experimental group

Description:

Aprepitant 200 mg/ oxycodone 0 IN 0 PO

Treatment:

Drug: Oxycodone 0mg, p.o.

Drug: Oxycodone 0mg, IN

Drug: Aprepitant 200mg

Aprepitant 200 mg/ oxycodone 0 IN 20 PO

Experimental group

Description:

Aprepitant 200 mg/ oxycodone 0 IN 20 PO

Treatment:

Drug: Oxycodone 0mg, IN

Drug: Oxycodone 20mg, p.o.

Drug: Aprepitant 200mg

Aprepitant 200 mg/ oxycodone 0 IN 40 PO

Experimental group

Description:

Aprepitant 200 mg/ oxycodone 0 IN 40 PO

Treatment:

Drug: Oxycodone 0mg, IN

Drug: Aprepitant 200mg

Drug: Oxycodone 40mg, p.o.

Aprepitant 200 mg/ oxycodone 15 IN 0 PO

Experimental group

Description:

Aprepitant 200 mg/ oxycodone 15 IN 0 PO

Treatment:

Drug: Oxycodone 0mg, p.o.

Drug: Oxycodone 15mg, IN

Drug: Aprepitant 200mg

Aprepitant 200 mg/ oxycodone 30 IN 0 PO

Experimental group

Description:

Aprepitant 200 mg/ oxycodone 30 IN 0 PO

Treatment:

Drug: Oxycodone 0mg, p.o.

Drug: Aprepitant 200mg

Drug: Oxycodone 30mg, IN

Sponsors of this trial

Lead Sponsor

Sharon Walsh

Collaborating Sponsors

National Institutes of Health (NIH)

Merck Sharp & Dohme (MSD)