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

Primary Purpose

Gastroesophageal Reflux Disease

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Pantoprazole
Sponsored by
Phillip Brian Smith
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Gastroesophageal Reflux Disease focused on measuring obese, children, adolescents, GERD, pharmacokinetic

Eligibility Criteria

6 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Arkansas
  • Children's Mercy Hospital
  • East Carolina University
  • University of Utah

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Pantoprazole

Arm Description

Outcomes

Primary Outcome Measures

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.
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.
PK Sampling
Total number of fresh plasma samples (all participants)
Drug Concentration in Plasma Samples
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).
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.
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.
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.
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.
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.

Secondary Outcome Measures

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).

Full Information

First Posted
July 3, 2014
Last Updated
September 9, 2019
Sponsor
Phillip Brian Smith
Collaborators
The Emmes Company, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT02186652
Brief Title
PK Study With Pantoprazole in Obese Children and Adolescents
Acronym
PAN01
Official Title
The Effect of Obesity on the Pharmacokinetics of Pantoprazole in Children and Adolescents
Study Type
Interventional

2. Study Status

Record Verification Date
September 2019
Overall Recruitment Status
Completed
Study Start Date
June 4, 2014 (Actual)
Primary Completion Date
September 13, 2015 (Actual)
Study Completion Date
September 13, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Phillip Brian Smith
Collaborators
The Emmes Company, LLC

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastroesophageal Reflux Disease
Keywords
obese, children, adolescents, GERD, pharmacokinetic

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
41 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pantoprazole
Arm Type
Other
Intervention Type
Drug
Intervention Name(s)
Pantoprazole
Primary Outcome Measure Information:
Title
Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (Cmax).
Description
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.
Time Frame
pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours
Title
Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (Tmax).
Description
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.
Time Frame
pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours
Title
PK Sampling
Description
Total number of fresh plasma samples (all participants)
Time Frame
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
Title
Drug Concentration in Plasma Samples
Description
Concentration of panto in plasma and concentration of panto sulfone in plasma
Time Frame
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
Title
Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (AUC).
Description
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.
Time Frame
pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours
Title
Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (AUC).
Description
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.
Time Frame
pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours
Title
Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (CL/F).
Description
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.
Time Frame
pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours
Title
Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (Vd/F).
Description
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.
Time Frame
pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours
Title
Pharmacokinetic Analysis in Obese Children After One Single Oral Dose of Pantoprazole (Vd/F).
Description
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.
Time Frame
pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, & 8 hours
Secondary Outcome Measure Information:
Title
The CYP2C19 Genotype and Its Association With CYP2C19 Phenotype
Description
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).
Time Frame
0, 1, 2, 3, 4, 6, 8, 12 hours post-dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Phillip B Smith, MD
Organizational Affiliation
Duke Clinical Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Arkansas
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72202
Country
United States
Facility Name
Children's Mercy Hospital
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
East Carolina University
City
Greenville
State/Province
North Carolina
ZIP/Postal Code
27834
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84108
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
29389444
Citation
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.
Results Reference
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PK Study With Pantoprazole in Obese Children and Adolescents

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