OXY-2: The Pharmacogenetics of Oxycodone Analgesia in Human Experimental Pain Models

Healthy Clinical Trial

Official title:

The Pharmacogenetics of Oxycodone Analgesia in Human Experimental Pain Models

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00271973
• Other study ID #: EudraCT 2005-004082-42
• Status: Completed
• Phase: Phase 4
• First received: January 3, 2006
• Last updated: January 29, 2007
• Start date: February 2006
• Est. completion date: January 2007

Study information

• Verified date: January 2007
• Source: Odense University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Medicines Agency
• Study type: Interventional

Clinical Trial Summary

Thirty-two healthy volunteers will be submitted to experimental pain and on the 2 study days receive Oxycodone 20 mg po vs. placebo. Half of the volunteers will be poor metabolizers according to CYP2D6 genotype and half will be extensive metabolizers (EM) and have an enzyme with normal function. The study hypothesis is that PM will experience less pain relief than EM.

Description:

Oxycodone is a semi-synthetic opioid with an analgesic effect in the postoperative pain management comparable to morphine. Oxycodone is N-demethylated by CYP2D6 to its active metabolite oxymorphone, a potent μ-receptor agonist. A genetic polymorphism divides a Caucasian population into two groups: 8% with an enzyme lacking activity, poor metabolizers (PM) and the rest with normal CYP2D6 activity, extensive metabolizers (EM).

Many different, single nucleotide polymorphisms (SNPs) are responsible for interindividual differences in the effect of opioids. Among these are the A118G SNP in the μ-receptor gene OPRM1 and the C3435T and G2677T/A SNPs in the MDR-1 gene of P-glycoprotein. P-glycoprotein is responsible for the absorption, excretion and transport of many drugs including opioids over the blood-brain barrier.

Electrical stimulation and cold pressor test are among the most well defined and evaluated human experimental pain models. The 32 volunteers will be submitted to the tests before and 1, 2, 3 and 4 hours after medicine intake.

To determine the plasma levels of Oxycodone and its metabolites blood will be drawn after each pain test. Also the CYP2D6 genotype and the above mentioned SNPs will be determined from the blood samples.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: January 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 20 Years to 40 Years

Eligibility

Inclusion Criteria:

• Healthy volunteer age between 20 and 40 years.

• Healthy according to medical history and physical examination.

• Informed consent given.

• Phenotyped or genotyped as extensive or poor metabolizer of sparteine.

• Female: Use of safe contraception (IUD, gestagen injectiones or oral contraceptive) or negative u-HCG test.

Exclusion Criteria:

• Any known allergy or intolerance to oxycodone.

• Regularly drug therapy or medication (except contraceptives).

• Alcohol or medicine abuse.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Oxycodone

Locations

Country	Name	City	State
Denmark	University of Southern Denmark, IST Clinical Pharmacology	Odense	Odense C

Sponsors (1)

Lead Sponsor	Collaborator
Odense University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pain threshold and tolerance measured by electrical stimulation and pain intensity measured by cold pressor test.
Secondary	The above compared to SNPs. Plasma levels of oxycodone and metabolites.