Population Pharmacokinetics and Pharmacogenomics of Oral Oxycodone in Thai Pediatric Surgical Patients

NCT03145272 | Unknown Phase 4 DMC

• 1 other identifier: SI407/2016
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Pharmacokinetics; Pharmacogenomics; Oxycodone

Keywords

Pharmacogenomics; Pharmacokinetics; Oxycodone

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetics metric (serum level of oxycodone and its metabolites at different time points)

  Oxycodone, oxymorphone, noroxymorphone and noroxycodone serum levels \[ Time Frame: The 10 samples will be drawn at the following time points: 8 blood samples will be taken at 30 minutes, 1, 1.5, 2, 3, 4, 5, and 6 hours post-dose in every patient along other 2 samples at approximately either 8 and 12 or 10 and 24 hours post-dose. \] Oxycodone, oxymorphone, noroxymorphone and noroxycodone levels in blood (ng/ml), at 10 time points, will be used to determine the effects of single-dose oral oxycodone administration in children.

  Up to 24 hours

Study Arms (1)

Age group

EXPERIMENTAL

An orogastric tube will be placed in the stomach (placement verified by routine accepted clinical guidelines) 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. This arm can be divided into 2 subgroups; (1)12 months - 1.9 years age group. (2) 2 - 5.9 years age group.

Drug: Oxycodone

Interventions

Oxycodone DRUG

A single weight-adjusted oxycodone dose of 0.1 mg/kg is administered as per standard clinical dosing guidelines

Age group

Eligibility Criteria

• Age: 1 Year - 6 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Inpatient who scheduled for non-emergency surgery
• Aged between 1 - 6 years
• Healthy volunteer
• Body weight more than 4.5 kilograms
• Opioid naive
• Schedule for pediatric non- GI tract surgery

You may not qualify if:

• Currently taking CYP 3A4 or CYP 2D6 inhibitors/inducers
• Known history of allergy to oxycodone
• Known GI, hepatic, or renal dysfunction
• Known sleep apnea or impaired respiratory reserve

Sponsors & Collaborators

• Mahidol University: lead

Study Sites (1)

Faculty of Medicine, Siriraj hospital

Bangkok Noi, Bangkok, 10700, Thailand

Location

MeSH Terms

Interventions

Oxycodone

Intervention Hierarchy (Ancestors)

Codeine; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Patcharee Srisawasdi, MD

  Mahidol University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2017
• First Posted: May 9, 2017
• Study Start: October 8, 2018
• Primary Completion: August 1, 2020
• Study Completion: December 1, 2023
• Last Updated: March 21, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

TH (1)