CELECOXIB Plasma and Cerebral Spinal Fluid Pharmacokinetics in Children

NCT01344200 | Recruiting Phase 2 DMC

• 1 other identifier: 09/09E
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

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

Keywords

Pharmacokinetics; Celecoxib; Children; Pharmacogenetic; ABCB1 genotype; CYP2C9 genotype; CSF; Plasma

Outcome Measures

Primary Outcomes (4)

• 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

  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.

  Compare mean celecoxib total and unbound plasma concentration (ug/L) post ingestion of 7 or 14 mg/kg celecoxib

  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.

  Compare mean celecoxib CSF concentration (ug/L) post ingestion of 7 or 14 mg/kg celecoxib

  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.

  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.

  Day 0, the day of the procedure, after taking study medication.

Secondary Outcomes (13)

• Ratio CSF/unbound plasma concentration

  Day 0, the day of the procedure, after taking study medication.

• Determine Peak Plasma concentration value (Cmax)

  Day 0, the day of the procedure, after taking study medication.

• Determine Area under the plasma concentration versus time curve (AUC)

  Day 0, the day of the procedure, after taking study medication.

• Determine apparent oral volume of distribution (Vd/F [L/kg])

  Day 0, the day of the procedure, after taking study medication.

• Determine apparent oral clearance (CL/F [L∙h-1∙kg-1]

  Day 0, the day of the procedure, after taking study medication.

Study Arms (5)

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

ACTIVE COMPARATOR

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.

Drug: Celecoxib

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

ACTIVE COMPARATOR

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.

Drug: Celecoxib

Phase II: Group A: Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

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

ACTIVE COMPARATOR

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.

Drug: Celecoxib

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

ACTIVE COMPARATOR

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.

Drug: Celecoxib

Interventions

Celecoxib DRUG

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.

Also known as: Celebrex

Phase I: Study drug Group 1 (Celecoxib 7 mg/kg); Phase I: Study drug Group 2 (Celecoxib 14 mg/kg); Phase II: Group B: Study drug (Celecoxib 7 mg/kg); Phase II: Group C: Study drug (Celecoxib 14 mg/kg)

Placebo DRUG

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.

Phase II: Group A: Placebo

Eligibility Criteria

• Age: 2 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• Age \< 2yrs and \>12yrs old
• Children with non-hematologic malignancies
• AML
• Children undergoing a bone marrow aspiration (BMA) only
• Serum creatinine \> 2 X UNL (upper normal limit) within 30 days
• Abnormal liver function; alanine aminotransferase (ALT) \> 2 X UNL, Aspartate aminotransferase (AST) \> 2 X UNL, total \& direct bilirubin \> 2 X UNL within 30 days
• History of peptic ulcer disease
• Allergy to celecoxib or NSAIDs (note: sulpha allergy does not exclude celecoxib)
• Recent (within 7 days) celecoxib ingestion
• Patients receiving CYP2C9 inhibitors fluconazole, amiodarone, oxandrolone
• Patients receiving CYP2C9 inducers rifampin and phenobarbitol
• Patients receiving high (≥ 5 gm/m2) and/ or escalating doses of methotrexate.
• Extremes of body mass index (BMI) (BMI \<5th percentile or \>95th percentile)
• Parents of any participants, irrespective of age, who are unable to read and understand instructions relayed in English or French
• 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

Sponsors & Collaborators

• Children's Hospital of Eastern Ontario: lead

Study Sites (1)

Children's Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

RECRUITING

Related Links

• Link to Children's Hospital of Eastern Ontario anesthesiology research page.

MeSH Terms

Interventions

Celecoxib

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Dr Kimmo Murto, MD

  Children's Hospital of Eastern Ontario

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dr Kimmo Murto, MD

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Research, Department of Anesthesiology & Pain Medicine

Study Record Dates

• First Submitted: April 21, 2011
• First Posted: April 29, 2011
• Study Start: January 29, 2024
• Primary Completion: January 31, 2026
• Study Completion (Estimated): February 1, 2027
• Last Updated: February 8, 2024

Record last verified: 2024-02

Locations

CA (1)