PK Study With Pantoprazole in Obese Children and Adolescents

Study Overview
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Brief Summary
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Multicenter, comparative single-dose pharmacokinetic (PK) study

Detailed Description
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Evaluate the pharmacokinetics of pantoprazole in obese children and adolescents with gastroesophageal reflux disease (GERD) following administration of an oral dose of pantoprazole.

Official Title
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The Effect of Obesity on the Pharmacokinetics of Pantoprazole in Children and Adolescents

Conditions
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Gastroesophageal Reflux Disease

Intervention / Treatment
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* Drug: Pantoprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant is between 6 and 17 (inclusive) years of age at the time of consent BMI ≥95th percentile Diagnosis of GERD established prior to 7 days before receipt of study drug dose defined as 1 or more of the following: clinical symptoms consistent with GERD as determined by the investigator a diagnosis of erosive esophagitis by endoscopy esophageal biopsy with histopathology consistent with reflux esophagitis abnormal pH-metry consistent with reflux esophagitis other test result consistent with GERD Written informed consent from the parent or legally authorized representative/guardian and participant assent per local IRB recommendation of age-appropriate consent and assent requirements Exclusion Criteria: Use of pantoprazole, lansoprazole, omeprazole, esomeprazole or rabeprazole within 48 hours prior to dose of study drug Use of fluoxetine, fluvoxamine, ketoconazole, ticlopidine, felbamate, topiramate, valproic acid, phenobarbital, carbamazepine, erythromycin, clarithromycin, grapefruit juice, verapamil, diltiazem, cimetidine, St. John's Wort, rifampin, rifapentine within seven days prior to dose of study drug Consumption of food after midnight on the day of the baseline visit Symptomatic asthma Type I diabetes History of adverse reaction to PPI Impaired hepatic activity as defined as any of the following: AST ≥150 IU/L, ALT ≥150 IU/L, total bilirubin ≥2.0 mg/dl, or alkaline phosphatase ≥600 IU/L Serum creatinine ≥2.0 mg/dL For females of childbearing potential, a positive pregnancy test result Known infection with hepatitis B, C, or HIV Any other condition that, in the opinion of the principal investigator, makes participation unadvised or unsafe.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Pantoprazole<br> | Drug: Pantoprazole<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (Cmax). | The pharmacokinetic blood samples will be 1.0 ml each and collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours after receiving one dose of Pantoprazole study drug. For those subjects with the poor metabolizer CYP2C19 genotype, an additional PK sample will be obtained at 12 hours after dosing. Here we report Cmax. | pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours | 
| Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (Tmax). | The pharmacokinetic blood samples will be 1.0 ml each and collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours after receiving one dose of Pantoprazole study drug. For those subjects with the poor metabolizer CYP2C19 genotype, an additional PK sample will be obtained at 12 hours after dosing. Here we report Tmax. | pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours | 
| PK Sampling | Total number of fresh plasma samples (all participants) | Pre-dose (within 30 minutes), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (±10 minutes) after dosing | 
| Drug Concentration in Plasma Samples | Concentration of panto in plasma and concentration of panto sulfone in plasma | Pre-dose (within 30 minutes), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (±10 minutes) after dosing | 
| Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (AUC). | The pharmacokinetic blood samples will be 1.0 ml each and collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours after receiving one dose of Pantoprazole study drug. For those subjects with the poor metabolizer CYP2C19 genotype, an additional PK sample will be obtained at 12 hours after dosing. Here we report AUC TBW. | pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours | 
| Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (AUC). | The pharmacokinetic blood samples will be 1.0 ml each and collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours after receiving one dose of Pantoprazole study drug. For those subjects with the poor metabolizer CYP2C19 genotype, an additional PK sample will be obtained at 12 hours after dosing. Here we report AUC LBW. | pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours | 
| Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (CL/F). | The pharmacokinetic blood samples will be 1.0 ml each and collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours after receiving one dose of Pantoprazole study drug. For those subjects with the poor metabolizer CYP2C19 genotype, an additional PK sample will be obtained at 12 hours after dosing. Here we report CL/F TBW. | pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours | 
| Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (Vd/F). | The pharmacokinetic blood samples will be 1.0 ml each and collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours after receiving one dose of Pantoprazole study drug. For those subjects with the poor metabolizer CYP2C19 genotype, an additional PK sample will be obtained at 12 hours after dosing. Here we report Vd/F TBW. | pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours | 
| Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (Vd/F). | The pharmacokinetic blood samples will be 1.0 ml each and collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours after receiving one dose of Pantoprazole study drug. For those subjects with the poor metabolizer CYP2C19 genotype, an additional PK sample will be obtained at 12 hours after dosing. Here we report Vd/F LBW. | pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The CYP2C19 Genotype and Its Association With CYP2C19 Phenotype | To examine the association of CYP2C19 genotype and its association with CYP2C19 phenotypes. To characterize the ability of the CYP2C19 genotype to predict pantoprazole plasma clearance, a correlation with CYP2C19 phenotype was explored using both standard linear and nonlinear regression techniques and their respective tests for significance and goodness of fit. In addition, the impact of all covariates on pantoprazole systemic exposure and apparent plasma clearance (e.g., demographic determinants of extent of obesity such as the waist:hip ratio, CYP2C19 genotype, BMI, and REE) was explored using validated population-based PK methods (NONMEM). | 0, 1, 2, 3, 4, 6, 8, 12 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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obese, children, adolescents, GERD, pharmacokinetic