PK Study With Pantoprazole in Obese Children and Adolescents

Phase 1

Completed

• Conditions: Gastroesophageal Reflux Disease
• Interventions: Drug: Pantoprazole

• Registration Number: NCT02186652
• Lead Sponsor: Phillip Brian Smith

Brief Summary

Multicenter, comparative single-dose pharmacokinetic (PK) study

Detailed Description

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

Study Timeline

• Study Start: 2014-06-04
• Study First Submitted: 2014-07-03
• Study First Submitted QC: 2014-07-08
• Study First Posted: 2014-07-10
• Primary Completion: 2015-09-13
• Study Completion: 2015-09-13
• Results First Submitted: 2018-09-24
• Results First Submitted QC: 2019-08-02
• Results First Posted: 2019-08-05
• Status Verified: 2019-09
• Last Update Submitted: 2019-09-09
• Last Update Posted: 2019-09-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 41

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Pantoprazole	Pantoprazole	-

Primary Outcome Measures

Name	Time	Method
Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (Cmax).	pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours	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.
Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (Tmax).	pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours	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.
PK Sampling	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	Total number of fresh plasma samples (all participants)
Drug Concentration in Plasma Samples	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	Concentration of panto in plasma and concentration of panto sulfone in plasma
Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (AUC).	pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours	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.
Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (CL/F).	pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours	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.
Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (Vd/F).	pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours	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.

Secondary Outcome Measures

Name	Time	Method
The CYP2C19 Genotype and Its Association With CYP2C19 Phenotype	0, 1, 2, 3, 4, 6, 8, 12 hours post-dose	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).

Trial Locations

Locations (4)

University of Arkansas; 🇺🇸 Little Rock, Arkansas, United States

Children's Mercy Hospital; 🇺🇸 Kansas City, Missouri, United States

East Carolina University; 🇺🇸 Greenville, North Carolina, United States

University of Utah; 🇺🇸 Salt Lake City, Utah, United States