Clinical trial NCT00271973: OXY-2: The Pharmacogenetics of Oxycodone Analgesia in Human Experimental Pain Models
Official title: The Pharmacogenetics of Oxycodone Analgesia in Human Experimental Pain Models
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Healthy
Lead sponsor: Odense University Hospital
Sponsor class: OTHER
First posted: 2006-01-04
Enrollment: 32
Sex: ALL
Minimum age (years): 20
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.

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 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.

Primary outcomes:
measure: Pain threshold and tolerance measured by electrical stimulation and pain intensity measured by cold pressor test.
Secondary outcomes:
measure: The above compared to SNPs. Plasma levels of oxycodone and metabolites.
Other outcomes:
Locations:
city: Odense
country: Denmark
facility: University of Southern Denmark, IST Clinical Pharmacology
state: Odense C
Study officials:
affiliation: University of Southern Denmark
name: Stine T. Zwisler, Dr.
role: PRINCIPAL_INVESTIGATOR
References: