Population Pharmacokinetic-Pharmacodynamic Study of Intravenous Oxycodone in Children

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ClinicalTrials.gov Identifier: NCT02728648

Recruitment Status : Suspended (Difficult to recruit patients)

First Posted : April 5, 2016

Last Update Posted : April 22, 2019

Sponsor:

Information provided by (Responsible Party):

Chaw Sook Hui, University of Malaya

Study Description

Brief Summary:

Oxycodone has been in clinical use for decades. It is an effective alternative to morphine for moderate to severe acute or chronic pain and has been found to improve quality of life. The drug has been used parenterally or orally as perioperative analgesia or for cancer pain relief. Despite its long clinical experience, prescribing errors and misuse may lead to addiction and accidental overdose. Currently, little is known about the pharmacokinetic properties of intravenous oxycodone among paediatric patients in this region even though the drug has been used in children in other countries such as Finland. Therefore, a pharmacokinetic-pharmacodynamic study of oxycodone among Malaysian pediatric patients is warranted.

Condition or disease	Intervention/treatment	Phase
Pain	Drug: Oxycodone	Phase 4

Detailed Description:

Oxycodone (14-hydroxy-7,8 dihydrocodeinone) is a strong, semisynthetic thebaine derivative µ-opioid receptor agonist. This drug is an effective alternative to morphine for moderate-to-severe pain. Oxycodone has been used parenterally or orally for perioperative analgesia or for cancer pain relief. The drug has a longer analgesic action than morphine. In terms of analgesic potency, intravenous oxycodone is about 1.6 times

The adverse effects of oxycodone are mostly similar to those of other opioids. Oxycodone, however, does not cause histamine release. The drug induces less nausea and vomiting, less sedating, and less central nervous system excitatory effects than morphine.

A large between-subject variability in pharmacokinetic properties of oxycodone has been observed. The variability could be attributed to the different body size and age-related difference in drug elimination organ system function. A 2-compartment first-order open model describes oxycodone pharmacokinetics in Finnish children (age 5.4±2.1 years) after an intravenous bolus dose of 0.1 mg kg-1 for post ophthalmic surgery pain relief. The authors reported a mean clearance (CL) and the steady-state volume of distribution (Vss) of oxycodone 15.2 mL min-1 kg-1 (0.912 L h-1 kg-1) and 2.1 L kg-1 respectively. A greater ventilator depression than comparable analgesic doses of other opioids was also observed. A pharmacokinetic study carried out in 9 young Finnish adult surgical patients reveals a clearance of 0.78 L min-1 (46.8 L h-1) and a volume of distribution (V) of 2.60 L kg-1. The mean AUC( t=0,12) ratio of noroxycodone (main metabolite) to oxycodone is 0.33. In a study on 69 Japanese adults (mean age 66 years, mean weight 52.8 kg) receiving intravenous oxycodone for cancer pain relief, a one-compartment first-order open model describes the pharmacokinetics of oxycodone. The mean CL and volume of distribution (V) are 24.6 L h-1 and 214 L or 4.053 L kg-1.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	80 participants
Allocation:	N/A
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Population Pharmacokinetic-Pharmacodynamic Study of Intravenous Oxycodone in Children
Actual Study Start Date :	April 2016
Actual Primary Completion Date :	April 2019
Estimated Study Completion Date :	December 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Oxycodone Oxycodone hydrochloride

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Active Open label IV Oxycodone 0.1 mg/kg Bolus Pharmacokinetic-Pharmacodynamic Study	Drug: Oxycodone Pain Management Other Name: OxyNorm

Outcome Measures

Primary Outcome Measures :

Clearance (CL) [ Time Frame: 18 months ]
Clearance: volume of plasma from which oxycodone is completely removed per unit time;

Secondary Outcome Measures :

Volume of distribution of IV oxycodone [ Time Frame: 18 months ]
Volume of distribution: theoretical volume that would be necessary to contain the total amount of oxycodone at the same concentration that it is observed in the blood plasma.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	3 Years to 17 Years (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Aged between 3 to 17 years
Generally healthy as documented by medical history (ASA 1-II)
Opioid-naïve
Patient is scheduled for a surgical procedure/procedures that is/are expected to require an analgesia with an opiate level medication.
Patient who will remain hospitalized for at least 24 hours after dosing with the study drug.
A negative urine pregnancy test at screening for females of childbearing potential

Exclusion Criteria:

Patient is a lactating or breastfeeding female
Patient has known allergy to oxycodone or any ingredient in oxycodone dosage form.

Contacts and Locations

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): NCT02728648

Locations

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Malaysia
Faculty of Medicine, University of Malaya
Kuala Lumpur, Wilayah Persekutuan, Malaysia, 50603

Sponsors and Collaborators

University of Malaya

Investigators

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Principal Investigator:	Sook Hui Chaw, M.Med	University of Malaya

More Information

Publications:

Kalso E, Pöyhiä R, Onnela P, Linko K, Tigerstedt I, Tammisto T. Intravenous morphine and oxycodone for pain after abdominal surgery. Acta Anaesthesiol Scand. 1991 Oct;35(7):642-6.

Olkkola KT, Hamunen K, Seppälä T, Maunuksela EL. Pharmacokinetics and ventilatory effects of intravenous oxycodone in postoperative children. Br J Clin Pharmacol. 1994 Jul;38(1):71-6.

Pöyhiä R, Olkkola KT, Seppälä T, Kalso E. The pharmacokinetics of oxycodone after intravenous injection in adults. Br J Clin Pharmacol. 1991 Oct;32(4):516-8.

Kokubun H, Yoshimoto T, Hojo M, Fukumura K, Matoba M. Pharmacokinetics of oxycodone after intravenous and subcutaneous administration in Japanese patients with cancer pain. J Pain Palliat Care Pharmacother. 2014 Dec;28(4):338-50. doi: 10.3109/15360288.2014.969872. Epub 2014 Oct 31.

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Responsible Party:	Chaw Sook Hui, Dr, University of Malaya
ClinicalTrials.gov Identifier:	NCT02728648
Other Study ID Numbers:	20162-2143
First Posted:	April 5, 2016 Key Record Dates
Last Update Posted:	April 22, 2019
Last Verified:	April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

Keywords provided by Chaw Sook Hui, University of Malaya:


Pain Management Pharmacokinetics Pharmacodynamics

Additional relevant MeSH terms:

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Oxycodone Analgesics, Opioid Narcotics Central Nervous System Depressants	Physiological Effects of Drugs Analgesics Sensory System Agents Peripheral Nervous System Agents

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