OXY-2: The Pharmacogenetics of Oxycodone Analgesia in Human Experimental Pain Models
Information source: Odense University Hospital
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Healthy
Intervention: Oxycodone (Drug)
Phase: Phase 4
Status: Completed
Sponsored by: Odense University Hospital Official(s) and/or principal investigator(s):
Stine T. Zwisler, Dr., Principal Investigator, Affiliation: University of Southern Denmark
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.
Clinical Details
Official title: The Pharmacogenetics of Oxycodone Analgesia in Human Experimental Pain Models
Study design: Treatment, Randomized, Double-Blind, Placebo Control, Crossover Assignment, Efficacy Study
Primary outcome: Pain threshold and tolerance measured by electrical stimulation and pain intensity measured by cold pressor test.
Secondary outcome: The above compared to SNPs. Plasma levels of oxycodone and metabolites.
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
Minimum age: 20 Years.
Maximum age: 40 Years.
Gender(s): Both.
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.
Locations and Contacts
University of Southern Denmark, IST Clinical Pharmacology, Odense, Odense C 5000, Denmark
Additional Information
Starting date: February 2006
Ending date: January 2007
Last updated: January 29, 2007
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