PK Study With Pantoprazole in Obese Children and Adolescents (PAN01)

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

Multicenter, comparative single-dose pharmacokinetic (PK) study

Study Overview

• Status: Completed
• Conditions: Gastroesophageal Reflux Disease
• Intervention / Treatment: Drug: Pantoprazole

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 Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • University of Arkansas
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • East Carolina University
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Pantoprazole	Drug: Pantoprazole

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Phillip Brian Smith
• Collaborators: The Emmes Company, LLC
• Investigators: Principal Investigator: Phillip B Smith, MD, Duke Clinical Research Institute

Publications and helpful links

General Publications

• Shakhnovich V, Smith PB, Guptill JT, James LP, Collier DN, Wu H, Livingston CE, Zhao J, Kearns GL; Best Pharmaceuticals for Children Act - Pediatric Trials Network. Obese Children Require Lower Doses of Pantoprazole Than Nonobese Peers to Achieve Equal Systemic Drug Exposures. J Pediatr. 2018 Feb;193:102-108.e1. doi: 10.1016/j.jpeds.2017.10.011.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2014
• Primary Completion (Actual): September 13, 2015
• Study Completion (Actual): September 13, 2015

Study Registration Dates

• First Submitted: July 3, 2014
• First Submitted That Met QC Criteria: July 8, 2014
• First Posted (Estimate): July 10, 2014

Study Record Updates

• Last Update Posted (Actual): September 17, 2019
• Last Update Submitted That Met QC Criteria: September 9, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: GERD; children; pharmacokinetic; adolescents; obese
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastroesophageal Reflux; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Pantoprazole
• Other Study ID Numbers: Pro00048765