CELECOXIB Plasma and Cerebral Spinal Fluid Pharmacokinetics in Children
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age2-12
SponsorChildren's Hospital of Eastern Ontario
About this trial
Celecoxib is effective for reducing postoperative pain in adults. Children use celecoxib more rapidly than adults and require higher doses. Celecoxib is partially metabolized in the liver by a certain enzyme. A person's genetic variation of this enzyme can influence how well their body uses Celecoxib. Furthermore, Celecoxib down-regulates P-glycoprotein (P-gp), a drug efflux transporter located at the blood brain barrier responsible for central nervous system (CNS) extrusion of ondansetron and possibly fentanyl; therefore celecoxib may augment the CNS effects of these drugs.
Understanding the blood and cerebrospinal fluid (CSF) profile of celecoxib in children and the influence of genetics on metabolism would help to develop appropriate celecoxib dosing in children for various treatment options.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
None
Disqualifiers
Age < 2yrs and >12yrs old
Children with non-hematologic malignancies
AML
Children undergoing a bone marrow aspiration (BMA) only
Trial design
Design model
Parallel
Treatments tested in this trial
Celecoxib
DrugIn Phase I twenty (20) children will receive either celecoxib 14 or 7 mg/kg 120-180 minutes prior to lumbar puncture (LP). In Phase II forty-five (45) children will receive celecoxib 14 mg/kg, 7 mg/kg or placebo in one of 5 time intervals, 1-24 hours prior to LP.
Placebo
DrugIn Phase II forty-five (45) children will receive celecoxib 14 mg/kg, 7 mg/kg or placebo in one of 5 time intervals, 1-24 hours prior to LP.
Treatment groups
65 Participants
are divided into 5 treatment groupsGroup A: Phase I: Study drug Group 1 (Celecoxib 7 mg/kg)Active comparator 1 intervention
Group B: Phase I: Study drug Group 2 (Celecoxib 14 mg/kg)Active comparator 1 intervention
Group C: Phase II: Group A: PlaceboPlacebo comparator 1 intervention
Group D: Phase II: Group B: Study drug (Celecoxib 7 mg/kg)Active comparator 1 intervention
Group E: Phase II: Group C: Study drug (Celecoxib 14 mg/kg)Active comparator 1 intervention
Trial outcomes
Primary outcomes
1
Mean celecoxib CSF concentration (ug/L) within 121-180 minutes post ingestion of 7 or 14 mg/kg celecoxib.
Compare mean celecoxib CSF concentration (ug/L) within 121-180 minutes post ingestion of 7 or 14 mg/kg celecoxib
Time frame
Day 0, the day of the procedure, after taking study medication.2
Mean celecoxib total and unbound plasma concentration (ug/L) in the following time intervals (mins): 0-30, 31- 60, 61- 90, 91- 120, 121-180, 181-300, 301-900 and 901-1440.
Compare mean celecoxib total and unbound plasma concentration (ug/L) post ingestion of 7 or 14 mg/kg celecoxib
Time frame
Day 0, the day of the procedure, after taking study medication.3
Mean celecoxib CSF concentration (ug/L) at the following time intervals (mins): 0-60, 61-120,121-180,181-300, 301-900 and 901-1440.
Compare mean celecoxib CSF concentration (ug/L) post ingestion of 7 or 14 mg/kg celecoxib
Time frame
Day 0, the day of the procedure, after taking study medication.4
Develop a PK model that explores the relationship between plasma and CSF celecoxib concentrations and the impact of covariates including age, weight and genetics using nonlinear mixed effects models.
The PK model will be used to see if there is a correlation between plasma and CSF celecoxib concentrations and various factors such as age, weight and genetics.
Time frame
Day 0, the day of the procedure, after taking study medication.Secondary outcomes
1
Ratio CSF/unbound plasma concentration
Ratio CSF/unbound plasma concentration at approximately the following time intervals (mins): 0-60, 61-120,121-180,181-300, 301-900 and 901-1440.
Time frame
Day 0, the day of the procedure, after taking study medication.2
Determine Peak Plasma concentration value (Cmax)
Primary outcomes 2-3 will be used to determine plasma and CSF mean +/- SD values for Maximum concentration (Cmax \[ug/L\])
Time frame
Day 0, the day of the procedure, after taking study medication.3
Determine Area under the plasma concentration versus time curve (AUC)
Primary outcomes 2-3 will be used to determine Area under concentration curve from time 0 to infinity (AUC (0-∞) \[ug/L∙h\]).
Time frame
Day 0, the day of the procedure, after taking study medication.4
Determine apparent oral volume of distribution (Vd/F [L/kg])
Primary outcomes 2-3 will be used to determine apparent oral volume of distribution (Vd/F \[L/kg\]).
Time frame
Day 0, the day of the procedure, after taking study medication.Sponsors and contacts
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Source ClinicalTrials.gov