Study Evaluating Pantoprazole Sodium Enteric-Coated Spheroid Suspension In Infants With Presumed GERD

A Multicenter, Randomized, Open Label, Single and Multiple Dose Study of the Pharmacokinetics and Pharmacodynamics of 2 Dose Levels of Pantoprazole Sodium Enteric-Coated Spheroid Suspension in Infants Aged 1 Through 11 Months With Presumed GERD

The purpose of this study is to characterize the pharmacokinetic (PK) and pharmacodynamic (PD) profiles to determine the safety and tolerability of single and multiple doses of pantoprazole in infants aged 1 through 11 months.

Study Overview

• Status: Completed
• Conditions: Gastroesophageal Reflux
• Intervention / Treatment: Drug: pantoprazole sodium enteric-coated spheroid suspension

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Brisbane, Australia
• Belgium
  • Antwerpen, Belgium, B-2020
  • Brussels, Belgium, B-1090
  • Gent, Belgium, B-9000
• France
  • Paris, France, 75674
• Germany
  • Aachen, Germany, D-52074
  • Osnabruck, Germany, D-49074
• Italy
  • Brescia, Italy, 25123
  • Naples, Italy, 80131
  • Roma, Italy, 00161
• Poland
  • Krakow, Poland, 30-663
  • Lodz, Poland, 91-738
  • Lublin, Poland
  • Warszaw, Poland, 04-730
• Switzerland
  • Zurich, Switzerland, 8032
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
  • California
    • Loma Linda, California, United States, 92351
    • San Diego, California, United States, 92103
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
  • Florida
    • Miami, Florida, United States, 33101
    • Pensacola, Florida, United States, 32504
  • Illinois
    • Chicago, Illinois, United States, 60614
    • Park Ridge, Illinois, United States, 60068
  • Kentucky
    • Louisville, Kentucky, United States, 40202
  • Louisiana
    • Shreveport, Louisiana, United States, 71130
  • Mississippi
    • Jackson, Mississippi, United States, 39216
  • Missouri
    • Kansas City, Missouri, United States, 64108
  • New York
    • New York, New York, United States, 10032
  • North Carolina
    • Durham, North Carolina, United States, 27710
  • Ohio
    • Cleveland, Ohio, United States, 44106
  • Texas
    • Temple, Texas, United States, 76508

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 11 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Greater than 44 weeks beyond neonatal period but less than 12 months
• Presumptive diagnosis of GERD
• Weight greater than 2.5 kg but less than 15 kg

Exclusion Criteria:

• History of gastrointestinal (GI) disorders, ie, unrepaired tracheal esophageal fistula, GI malabsorption
• Clinically significant medical or surgical abnormalities

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: High dose	Drug: pantoprazole sodium enteric-coated spheroid suspension; pediatric suspension taken daily x 7 days
Active Comparator: Low dose	Drug: pantoprazole sodium enteric-coated spheroid suspension; pediatric suspension taken daily x 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Concentration (Cmax)	Pharmacokinetic (PK) parameters, including peak plasma concentration, were determined following a single oral dose of pantoprazole	1 day
Time to Peak Concentration (Tmax) Profile	Pharmacokinetic (PK) parameters, including time to peak plasma concentration, were determined following a single oral dose of pantoprazole.	1 day
Disposition Half-life	Pharmacokinetic (PK) parameters, including the terminal-phase disposition half-life, were determined following a single oral dose of pantoprazole. Half-life is the time required for half the quantity of absorbed drug to be metabolized or eliminated by normal biological processes.	1 day
Area Under the Concentration-time Curve (AUC)	Pharmacokinetic (PK) parameters, including AUC, were determined following a single oral dose of pantoprazole. AUC is a measure of the plasma concentration of the drug over time. It is used to characterize drug absorption.	1 day
Apparent Oral Clearance (CL/F)	Pharmacokinetic (PK) parameters, including apparent oral clearance, were determined following a single oral dose of pantoprazole. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.	1 day
Pantoprazole Plasma Concentration After Multiple-Dose Oral Administration	Plasma concentration of pantoprazole after multiple doses was measured to see if there was any accumulation of the drug.	7 days
Intragastric pH	Intragastric pH is a method for evaluating gastric acidity scaled 0-9. A lower pH means more acidity. A longer duration of esophageal mucosa exposure to a gastric refluxate with a pH <4.0 correlates with more severe mucosal injury in patients with gastroesophageal reflux disease (GERD).	7 days
Median Intragastric pH	Intragastric pH is a method for evaluating gastric acidity scaled 0-9. A lower pH means more acidity. A longer duration of esophageal mucosa exposure to a gastric refluxate with a pH <4.0 correlates with more severe mucosal injury in patients with gastroesophageal reflux disease (GERD).	7 days
Percentage of Time Intragastric pH Was >4	Intragastric pH is a method for evaluating gastric acidity. A lower pH means more acidity. A longer duration of esophageal mucosa exposure to a gastric refluxate with a pH <4.0 correlates with more severe mucosal injury in patients with gastroesophageal reflux disease (GERD).	7 days
Mean Intraesophageal pH	Intraesophagel pH is a method for evaluating acidity of gastric refluxate scaled 0-9. A lower pH means more acidity. A longer duration of esophageal mucosa exposure to a gastric refluxate with a pH <4.0 correlates with more severe mucosal injury in patients with gastroesophageal reflux disease (GERD).	7 days
Median Intraesophageal pH	Intraesophagel pH is a method for evaluating acidity of gastric refluxate scaled 0-9. A lower pH means more acidity. A longer duration of esophageal mucosa exposure to a gastric refluxate with a pH <4.0 correlates with more severe mucosal injury in patients with gastroesophageal reflux disease (GERD).	7 days
Percentage of Time That Intraesophageal pH Was <4	Intraesophagel pH is a method for evaluating acidity of gastric refluxate. A lower pH means more acidity. A longer duration of esophageal mucosa exposure to a gastric refluxate with a pH <4.0 correlates with more severe mucosal injury in patients with gastroesophageal reflux disease (GERD).	7 days
Normalized Area of Gastric Hydrogen Ion Activity Over Time	Normalized Area of Gastric Hydrogen Ion Activity Over Time is a measure of the area under the curve of the gastric hydrogen ion activity over time, which is normalized for a 24-hour period.	7 days
Normalized Area of Esophageal Hydrogen Ion Activity Over Time	Normalized Area of Esophageal Hydrogen Ion Activity Over Time is a measure of the area under the curve of the esophageal hydrogen ion activity over time, which is normalized for a 24-hour period.	7 days

Collaborators and Investigators

• Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer
• Collaborators: Nycomed
• Investigators: Principal Investigator: Trial Manager, For Australia, medinfo@wyeth.com; Principal Investigator: Trial Manager, For Poland, WPWZMED@wyeth.com; Principal Investigator: Trial Manager, For Switzerland, med@wyeth.com

Publications and helpful links

General Publications

• Tammara BK, Sullivan JE, Adcock KG, Kierkus J, Giblin J, Rath N, Meng X, Maguire MK, Comer GM, Ward RM. Randomized, open-label, multicentre pharmacokinetic studies of two dose levels of pantoprazole granules in infants and children aged 1 month through <6 years with gastro-oesophageal reflux disease. Clin Pharmacokinet. 2011 Aug;50(8):541-50. doi: 10.2165/11591900-000000000-00000.

Study record dates

Study Major Dates

• Study Start: November 1, 2005
• Primary Completion (Actual): March 1, 2008
• Study Completion (Actual): March 1, 2008

Study Registration Dates

• First Submitted: November 23, 2005
• First Submitted That Met QC Criteria: November 23, 2005
• First Posted (Estimate): November 28, 2005

Study Record Updates

• Last Update Posted (Estimate): May 7, 2010
• Last Update Submitted That Met QC Criteria: April 19, 2010
• Last Verified: April 1, 2010

More Information

Terms related to this study

• Keywords: GERD; Infant
• 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: 3001B3-333, 3001B3-335