Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03145272
Recruitment Status : Recruiting
First Posted : May 9, 2017
Last Update Posted : February 15, 2019
Sponsor:
Information provided by (Responsible Party):
Mahidol University

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.


Condition or disease Intervention/treatment Phase
Pharmacokinetics Pharmacogenomics Oxycodone Drug: Oxycodone Phase 4

Detailed 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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pharmacokinetics and Pharmacogenomics of Oral Oxycodone in Thai Pediatric Surgical Patients : a Pilot Study
Actual Study Start Date : October 8, 2018
Estimated Primary Completion Date : March 1, 2019
Estimated Study Completion Date : April 1, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Age group

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




Primary Outcome Measures :
  1. Pharmacokinetics metric (serum level of oxycodone and its metabolites at different time points) [ Time Frame: Up to 24 hours ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   1 Year to 6 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03145272


Contacts
Layout table for location contacts
Contact: Sirirat Rattanaarpa, MD 6681-909-9242 mednoonr@gmail.com
Contact: Patcharee Srisawasdi, MD 662419-7989 pat.si.research@gmail.com

Locations
Layout table for location information
Thailand
Faculty of Medicine, Siriraj hospital Recruiting
Bangkok Noi, Bangkok, Thailand, 10700
Contact: Sirirat Rattana-arpa, MD    +66819099242    mednoonr@gmail.com   
Contact: Taniga Kiatchai, MD    +66818140790    taniga@gmail.com   
Sponsors and Collaborators
Mahidol University
Investigators
Layout table for investigator information
Principal Investigator: Patcharee Srisawasdi, MD Mahidol University

Layout table for additonal information
Responsible Party: Mahidol University
ClinicalTrials.gov Identifier: NCT03145272     History of Changes
Other Study ID Numbers: SI407/2016
First Posted: May 9, 2017    Key Record Dates
Last Update Posted: February 15, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Mahidol University:
Pharmacogenomics
Pharmacokinetics
Oxycodone

Additional relevant MeSH terms:
Layout table for MeSH terms
Oxycodone
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents