How genetics may impact the metabolism and elimination of celecoxib from the body and brain of children

ISRCTN	ISRCTN07429476
DOI	https://doi.org/10.1186/ISRCTN07429476
Protocol serial number	18/08SE
Sponsor	Children's Hospital of Eastern Ontario Research Institute (Canada)
Funder	University of Ottawa, Department of Anesthesiology, Chairman's Fund (Canada)

Submission date: 14/12/2008
Registration date: 06/10/2009
Last edited: 30/08/2011

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Kimmo Murto
Scientific

Children's Hospital of Eastern Ontario
401 Smyth Road
Ottawa
K1H8L1
Canada

Phone	+1 613 737 2431
Email	Kmurto@cheo.on.ca

Study information

Primary study design	Interventional
Study design	Randomised controlled single-centre trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	The impact of genotype on plasma and cerebral spinal fluid pharmacokinetics of celecoxib in children: a randomised controlled single-centre trial
Study objectives	1. The cerebral spinal fluid (CSF) concentration of celecoxib 3 hours post oral suspension ingestion is lower than plasma levels 2. The CSF peak concentration (Cmax) of celecoxib is delayed compared to plasma Cmax 3. The CSF concentration of celecoxib is directly related to the dose ingested and underlying P450 genotype 4. Blood and CSF celecoxib concentration is directly related to age 5. Oral celecoxib dosage is directly related to quality of life and inversely related to level of discomfort when administered prior to and one dose after a lumbar puncture (LP) +/- bone marrow biopsy (BM)
Ethics approval(s)	Children's Hospital of Eastern Ontario (CHEO) Research Ethics Board (ref: 09/10E). Approval pending as of 31/03/2009.
Health condition(s) or problem(s) studied	Haematological malignancy
Intervention	Cohort receives oral celecoxib 10 mg/kg 3 hours prior to first scheduled LP (LP 1) and then 5 mg/kg 12 hours after first dose and multiple blood samples to create blood PK profile. Randomisation into one of two groups (Group 1: CSF dose timing; Group 2: dose variation) prior to undergoing the remaining scheduled LPs (LPs 2-5). Group 1: Oral celecoxib 10 mg/kg either 60, 120, 300 or 900 mins prior to remaining 4 LPs followed by 5 mg/kg post first dose to create CSF PK profile. Group 2: Either oral celecoxib 6 mg/kg or 14 mg/kg on 2 occasions each 3 hours before LP and then 12 hours later to create truncated CSF and blood PK profiles at higher and lower doses.
Intervention type	Drug
Phase	Phase IV
Drug / device / biological / vaccine name(s)	Celecoxib
Primary outcome measure(s)	1. All patients and CSF dose timing cohort (Group 1: Oral celecoxib 10 mg/kg pharmacokinetic profile) 1.1. Mean total and unbound plasma concentration ug/L at approximately the following time intervals (mins): 30, 60, 90, 120, 180, 300, 900 1.2. Mean CSF concentration ug/L at approximately the following time intervals (mins): 60, 120, 180, 300, 900 1.3. Ratio CSF/unbound plasma concentration at approximately the following time intervals (mins): 60, 120, 180, 300, 900 1.4. This information will be used to determine plasma and CSF mean +/- SD values for maximum concentration (Cmax [ug/L]); area under concentration curve from time 0 to infinity; apparent oral volume of distribution (Vd/F [L/kg]); apparent oral clearance (CL/F [L·h-1·kg-1] and terminal elimination half-life (t1/2 [h]). A median value will be determined for time to maximum concentration (tmax[h]). 2. Dose escalation cohort (Group 2: Oral celecoxib 6 mg/kg and 14 mg/kg pharmacokinetic profile) 2.1. Mean total and unbound plasma concentration ug/L at approximately the following time intervals (mins): 60, 180, 300 2.2. Mean CSF concentration ug/L at approximately 180 min 2.3. Ratio CSF/unbound plasma concentration at approximately 180 min 2.4. This information in conjunction with the pharmacokinetic profile established in the dose timing cohort (10 mg/kg) will be used to predict plasma and CSF values for tmax, Cmax, AUC, Vd/F, CL/F and t1/2 for 6 and 14 mg/kg oral doses respectively.
Key secondary outcome measure(s)	1. Polymorphisms of genotypes CYP2C9 and CYP3A4 liver enzymes and correlations to drug levels 2. Pediatric Quality of life Inventory (PedsQL) version 4.0 scores before and 7 days after LP 2.1. Parent report for children aged 2-7, 8-12 and 13-18 2.2. Child report ages 8-12 and 13-18 3. PedsQL Cancer module version 3.0 scores before and 7 days after LP 3.1. Parent report for children aged 2-7, 8-12 and 13-18 3.2. Child report ages 8-12 and 13-18 4. PedsQL Multidimension Fatigue Scale version 1.0 scores before and 7 days after LP 4.1. Parent report for children aged 2-7, 8-12 and 13-18 4.2. Child report ages 8-12 and 13-18 5. PedsQL Pediatric Pain Questionnaire baseline and daily scores for 7 days after LP 5.1. Parent report for children aged 2-7, 8-12 and 13-18 5.2. Child report ages 5-7, 8-12 and 13-18 6. Demographics including professional identity of the individual performing the LP+/-BM, description of the LP and BM needles used, number of attempts and degree of difficulty 7. Adverse events recorded daily for 7 days after each dose ingested
Completion date	01/10/2011

Eligibility

Participant type(s)	Patient
Age group	Child
Lower age limit	2 Years
Upper age limit	18 Years
Sex	All
Target sample size at registration	20
Key inclusion criteria	Both males and females, age 2-18 years with haematological malignancy expected to undergo five lumbar punctures.
Key exclusion criteria	1. Serum creatinine >2 X upper normal limit (UNL) 2. Abnormal liver function; namely alanine aminotransferase (ALT) >1.5 X UNL, alkaline phosphatase (ALP) > 5X UNL, total bilirubin >2 X UNL 3. History of peptic ulcer disease 4. Allergy to celecoxib, sulfonamide compounds or non steroidal anti-inflammatory drugs (NSAIDs) 5. Patients receiving CYP2C9 inhibitors fluconazole, amiodarone and oxandrolone 6. Patients receiving CYP2C9 inducers rifampin and phenobarbitol 7. Extremes of body mass index (BMI) (age related below 10th or above 90th percentile) 8. Parents of any participants, irrespective of age, who are unable to read and understand instructions relayed in English or French 9. Participant and/or parents of any participants, irrespective of age, who suffer from dementia, psychosis, significant developmental delay or other impairment that would prohibit the understanding and giving of informed consent or assent or the participation in self-care or toxicity reporting
Date of first enrolment	01/04/2009
Date of final enrolment	01/10/2011

Locations

Countries of recruitment

Canada

Study participating centre

Children's Hospital of Eastern Ontario

Ottawa
K1H8L1
Canada

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes