Contact information
Type
Scientific
Primary contact
Dr Kimmo Murto
ORCID ID
Contact details
Children's Hospital of Eastern Ontario
401 Smyth Road
Ottawa
K1H8L1
Canada
+1 613 737 2431
Kmurto@cheo.on.ca
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
18/08SE
Study information
Scientific title
The impact of genotype on plasma and cerebral spinal fluid pharmacokinetics of celecoxib in children: a randomised controlled single-centre trial
Acronym
Study hypothesis
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
Children's Hospital of Eastern Ontario (CHEO) Research Ethics Board (ref: 09/10E). Approval pending as of 31/03/2009.
Study design
Randomised controlled single-centre trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
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 names
Celecoxib
Primary outcome measure
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.
Secondary outcome measures
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
Overall trial start date
01/04/2009
Overall trial end date
01/10/2011
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Both males and females, age 2-18 years with haematological malignancy expected to undergo five lumbar punctures.
Participant type
Patient
Age group
Child
Gender
Both
Target number of participants
20
Participant 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
Recruitment start date
01/04/2009
Recruitment end date
01/10/2011
Locations
Countries of recruitment
Canada
Trial participating centre
Children's Hospital of Eastern Ontario
Ottawa
K1H8L1
Canada
Sponsor information
Organisation
Children's Hospital of Eastern Ontario Research Institute (Canada)
Sponsor details
401 Smyth Road
Rm. 139
Ottawa
Ontario
K1H 8L1
Canada
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
University/education
Funder name
University of Ottawa, Department of Anesthesiology, Chairman's Fund (Canada)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list