Recruiting

Phase 2

CelecoxibCELECOXIB Plasma and Cerebral Spinal Fluid Pharmacokinetics in Children

Sponsor:

Children's Hospital of Eastern Ontario

Code:

NCT01344200

Conditions

Pharmacokinetics of Celecoxib in Children

Eligibility Criteria

Sex: All

Age: 2 - 12

Healthy Volunteers: Not accepted

Interventions

Celecoxib

Placebo

Study Details

Brief summary:

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.

Conditions

Pharmacokinetics of Celecoxib in Children

Study ID

NCT01344200

Start date

Jan 29, 2024

Status verified date

Feb, 2024

Completion date

Feb 1, 2027

Anticipated

Primary completion date

Jan 31, 2026

Anticipated

Eligibility Criteria

Sex: All

Age: 2 - 12

Healthy Volunteers: Not accepted

Inclusion Criteria:

Children aged 2-12 years, undergoing Maintenance phase chemotherapy for hematological malignancies and lymphomas (i.e. acute lymphoblastic leukemia \[ALL\] and lymphoblastic lymphomas \[LLy\] at CHEO. At this point, all patients would have achieved remission an average of 6 months earlier.

Exclusion Criteria:

1. Age < 2yrs and >12yrs old
2. Children with non-hematologic malignancies
3. AML
4. Children undergoing a bone marrow aspiration (BMA) only
5. Serum creatinine > 2 X UNL (upper normal limit) within 30 days
6. Abnormal liver function; alanine aminotransferase (ALT) > 2 X UNL, Aspartate aminotransferase (AST) > 2 X UNL, total \& direct bilirubin > 2 X UNL within 30 days
7. History of peptic ulcer disease
8. Allergy to celecoxib or NSAIDs (note: sulpha allergy does not exclude celecoxib)
9. Recent (within 7 days) celecoxib ingestion
10. Patients receiving CYP2C9 inhibitors fluconazole, amiodarone, oxandrolone
11. Patients receiving CYP2C9 inducers rifampin and phenobarbitol
12. Patients receiving high (≥ 5 gm/m2) and/ or escalating doses of methotrexate.
13. Extremes of body mass index (BMI) (BMI <5th percentile or >95th percentile)
14. Parents of any participants, irrespective of age, who are unable to read and understand instructions relayed in English or French
15. Participant and/or parents of any participants, irrespective of age, who suffer from dementia, psychosis or any impairment that would prohibit the understanding and giving of informed consent or study-related reporting
16. Patient enrolled in another trial
17. Pregnancy.

Study Design

Enrollment

65 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Phase I: Study drug Group 1 (Celecoxib 7 mg/kg)

Study participants randomized to this group will receive a single 7 mg/kg dose of celecoxib approximately 121-180 minutes before their scheduled LP ± BMA. The study medication will be a liquid and the study participant will be asked to drink it.

active comparator: Phase I: Study drug Group 2 (Celecoxib 14 mg/kg)

Study participants randomized to this group will receive a single 14 mg/kg dose of celecoxib approximately 121-180 minutes before their scheduled LP ± BMA. The study medication will be a liquid and the study participant will be asked to drink it.

placebo comparator: Phase II: Group A: Placebo

Study participants will receive a single dose of placebo. Placebo will be liquid. The study participant will drink it.

The timing of when the study participants in this group will take placebo will be determined in a second randomization:

Group A.1: will take placebo 15 to 24 hours prior to having their LP±BMA. The study medication will be taken at home.

Group A.2: will take placebo 5 to 15 hours prior to having their LP±BMA. The study medication will be taken at home.

Group A.3: will take the placebo 3 to 5 hours prior to having their LP±BMA. The study medication will be taken at home.

Group A.4: will take the study medication 1 to 2 hours prior to having their LP±BMA. The study medication will be taken at the hospital.

Group A.5: will take the study medication 0 to 60 minutes prior to having their LP±BMA. The study medication will be taken at the hospital.

active comparator: Phase II: Group B: Study drug (Celecoxib 7 mg/kg)

Study participants randomized to this group you will receive a single 7 mg/kg dose of celecoxib which will be in a liquid form, and the study participant will drink it.

The timing of when the study participant in this group will take this medication will be determined in a second randomization:

Group B.1: will take the study medication 15 to 24 hours prior to having their LP±BMA. The study medication will be taken at home.

Group B.2: will take the study medication 5 to 15 hours prior to having their LP±BMA. The study medication will be taken at home.

Group B.3: will take the study medication 3 to 5 hours prior to having their LP±BMA. The study medication will be taken at home.

Group B.4: will take the study medication 1 to 2 hours prior to having their LP±BMA. The study medication will be taken at the hospital.

Group B.5: will take the study medication 0 to 60 minutes prior to having your LP±BMA. The study medication will be taken at the hospital.

active comparator: Phase II: Group C: Study drug (Celecoxib 14 mg/kg)

Study participants randomized to this group you will receive a single 14 mg/kg dose of celecoxib which will be in a liquid form, and the study participant will drink it.

The timing of when the study participant in this group will take this medication will be determined in a second randomization:

Group C.1: will take the study medication 15 to 24 hours prior to having their LP±BMA. The study medication will be taken at home.

Group C.2: will take the study medication 5 to 15 hours prior to having their LP±BMA. The study medication will be taken at home.

Group C.3: will take the study medication 3 to 5 hours prior to having their LP±BMA. The study medication will be taken at home.

Group C.4: will take the study medication 1 to 2 hours prior to having your LP±BMA. The study medication will be taken at the hospital.

Group C.5: will take the study medication 0 to 60 minutes prior to having your LP±BMA. The study medication will be taken at the hospital.

Interventions

Celecoxib

In 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

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.

Primary outcome measure

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. ]
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. [ Time Frame: Day 0, the day of the procedure, after taking study medication. ]
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. [ Time Frame: Day 0, the day of the procedure, after taking study medication. ]
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. [ Time Frame: Day 0, the day of the procedure, after taking study medication. ]

Central Contacts and Locations

Central contacts

Dr Kimmo Murto, MD

613-737-7600 kmurto@cheo.on.ca

Locations

Children's Hospital of Eastern Ontario

Recruiting

Ottawa, Ontario, Canada, K1H 8L1

Contacts

Dr Kimmo Murto, MD

613-737-7600 kmurto@cheo.on.ca

Principal Investigator:

Dr Kimmo Murto, MD

More Information

Sponsor

Children's Hospital of Eastern Ontario

Last update posted

Feb 8, 2024

Last verified

Feb, 2024

Keywords

Pharmacokinetics
Celecoxib
Children
Pharmacogenetic
ABCB1 genotype
CYP2C9 genotype
CSF
Plasma

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Children's Hospital of Eastern Ontario on 2024-02-08.