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

Purpose

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.

Condition	Intervention	Phase
Healthy	Drug: Oxycodone	Phase IV

Drug Information available for:

Oxycodone Oxycodone hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double-Blind, Placebo Control, Crossover Assignment, Efficacy Study

Official Title:	The Pharmacogenetics of Oxycodone Analgesia in Human Experimental Pain Models

Further study details as provided by Odense University Hospital:

Primary Outcome Measures:

Pain threshold and tolerance measured by electrical stimulation and pain intensity measured by cold pressor test.

Secondary Outcome Measures:

The above compared to SNPs. Plasma levels of oxycodone and metabolites.

Estimated Enrollment:	32
Study Start Date:	February 2006
Estimated Study Completion Date:	January 2007

Detailed 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.

Eligibility

Ages Eligible for Study:	20 Years to 40 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00271973

Locations


Denmark, Odense C
	University of Southern Denmark, IST Clinical Pharmacology
	Odense, Odense C, Denmark, 5000

Sponsors and Collaborators

Odense University Hospital

Investigators


Principal Investigator:	Stine T. Zwisler, Dr.	University of Southern Denmark

More Information

Study ID Numbers:	EudraCT 2005-004082-42
First Received:	January 3, 2006
Last Updated:	January 29, 2007
ClinicalTrials.gov Identifier:	NCT00271973
Health Authority:	Denmark: Danish Medicines Agency