PK Study With Pantoprazole in Obese Children and Adolescents

Gastroesophageal Reflux Disease Clinical Trial

— PAN01  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02186652
• Other study ID #: Pro00048765
• Status: Completed
• Phase: Phase 1
• Start date: June 4, 2014
• Est. completion date: September 13, 2015

Study information

• Verified date: September 2019
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Multicenter, comparative single-dose pharmacokinetic (PK) study

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: September 13, 2015
• Est. primary completion date: September 13, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 17 Years

Eligibility

Inclusion Criteria:

1. Participant is between 6 and 17 (inclusive) years of age at the time of consent

2. BMI =95th percentile

3. Diagnosis of GERD established prior to 7 days before receipt of study drug dose defined as 1 or more of the following:

1. clinical symptoms consistent with GERD as determined by the investigator

2. a diagnosis of erosive esophagitis by endoscopy

3. esophageal biopsy with histopathology consistent with reflux esophagitis

4. abnormal pH-metry consistent with reflux esophagitis

5. other test result consistent with GERD

4. 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:

1. Use of pantoprazole, lansoprazole, omeprazole, esomeprazole or rabeprazole within 48 hours prior to dose of study drug

2. 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

3. Consumption of food after midnight on the day of the baseline visit

4. Symptomatic asthma

5. Type I diabetes

6. History of adverse reaction to PPI

7. 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

8. Serum creatinine =2.0 mg/dL

9. For females of childbearing potential, a positive pregnancy test result

10. Known infection with hepatitis B, C, or HIV

11. Any other condition that, in the opinion of the principal investigator, makes participation unadvised or unsafe.

Related Conditions & MeSH terms

• Gastroesophageal Reflux
• Gastroesophageal Reflux Disease

Intervention

Drug:
• Pantoprazole

Locations

Country	Name	City	State
United States	East Carolina University	Greenville	North Carolina
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	University of Arkansas	Little Rock	Arkansas
United States	University of Utah	Salt Lake City	Utah

Sponsors (2)

Lead Sponsor	Collaborator
Phillip Brian Smith	The Emmes Company, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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

External Links

•   Obese Children Require Lower Doses of Pantoprazole Than Nonobese Peers to Achieve Equal Systemic Drug Exposures