Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT03145272 |
| Other study ID # |
SI407/2016 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
October 8, 2018 |
| Est. completion date |
December 1, 2023 |
Study information
| Verified date |
March 2023 |
| Source |
Mahidol University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This study is designed as an experimental trial which collect prospective data at Mahidol
university. It aims to characterize the responses of Thai pediatric population,age 1 - 6
years, to oxycodone oral syrup and its metabolites (oxymorphone, noroxymorphone and
noroxycodone) with specific respect to the pharmacogenomics (How drug affects patients).
A total of 20 generally healthy, opioid-naive children, aged 1-6 years, scheduled as
in-patient surgery for non-emergency surgery, non-gastrointestinal tract surgery are
involved.
The patients are divide into 2 groups (1) 10 patients in 12 months - 1.9 years, and (2) 10
patients in the 2 - 5.9 years age group.
Every patient will receive inhalational or intravenous induction of anesthesia as decided by
the anesthesia team on the day of surgery, as is routine clinical care. An intravenous
cannula (IV) will be inserted in every patient as part of their routine clinical care. No
additional intravenous line will be required for this study.
As part of the study protocol, a blood sample (5 mL) will be taken from the IV and sent for
genetic analysis. (However, in order to limit the amount of blood drawn from small babies, 3
ml will be drawn, not 5 ml, if the patient is less than 6 months or less than 10kg.) The
genetic testing is specifically to analyze the following genotypes only: CYP2D6 and CYP3A4,
which represent the differences in cytochrome P450 metabolism of oxycodone.
An orogastric tube will be placed in the stomach under anesthesia as is part of standard
routine clinical care to remove gastric contents. The same orogastric tube will be used for
intragastric liquid oxycodone administration in a dose of 0.1 mg/kg before the surgical
incision. This weight-adjusted dose of 0.1 mg/kg is administered as per standard clinical
dosing guidelines. 10 blood samples (51mL/sample) will be taken from the IV and sent for
drug-level analysis. A total of 11 blood samples will be drawn for the study. The first
sample will be sent for genetic testing. The other 10 samples will be drawn at the following
time points: 30 minutes, 1, 1.5, 2, 3, 4, 5, and 6 hours post-dose in every patient and the
other 2 samples anytime between 6 and 24 hours post-dose .
Oxycodone, oxymorphone, noroxymorphone and noroxycodone levels, at 10 time points, will be
used to determine the individual responses to oxycodone. CYP2D6 genotype will be determined
to identify the ultra-rapid metabolizers.
Description:
Oxycodone is the most commonly used analgesic for the management of moderate and severe
postoperative pain. The efficacy of Oxycodone as a potent opioid has been confirmed in
children.
The principal metabolic pathway of oxycodone in humans is N-demethylation via enzyme CYP3A4
to generate inactive noroxycodone. A smaller amount (approximately 11%) is O-demethylated by
cytochrome P450 enzyme CYP2D6 to become oxymorphone, the active and potent metabolite which
exhibits about 40 times the affinity and 8 times the potency on μ-opioid receptors compared
to the mother substance. Approximate frequencies of cytochrome P450 enzyme CYP2D6 phenotypes
for the Caucasian population are: poor metabolizers 5 - 10%, extensive/intermediate
metabolizers 65-90%, and ultra-rapid metabolizers 5 - 10%. Kirchheiner and colleagues noticed
more codeine-related sedative side-effects in ultra-rapid metabolizers. In studies
investigating extensive and poor metabolizers, codeine side-effects do not seem to be related
to CYP2D6 genotype. However, clinical investigations of CYP2D6 genotype in the postoperative
pain setting have shown conflicting results, and well-designed prospective studies are
lacking. Taken together, these results demonstrate the need for careful pharmacokinetic
studies in children who received a pharmacologic agent, such as oxycodone, which is
metabolized by the enzyme CYP2D6.
The population PK of oxycodone and its metabolites has not been fully established for oral
oxycodone in pediatric patients. In addition, there is a group of ultra-rapid metabolizers
(approximately 4.5% of the population, but as high as 20% in some particular ethnic groups;
East African and Saudi Arabian populations) which may be at risk for serious side effects in
the commonly prescribed dose (which is extrapolated from adult recommendations). It is
important to further investigate oral oxycodone to optimize dosing recommendations.
