Gastroesophageal Reflux
Conditions
Keywords
GERD, Infant
Brief summary
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.
Interventions
DRUGpantoprazole sodium enteric-coated spheroid suspension
pediatric suspension taken daily x 7 days
Sponsors
Nycomed
Wyeth is now a wholly owned subsidiary of Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Months to 11 Months
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak Concentration (Cmax) | 1 day | Pharmacokinetic (PK) parameters, including peak plasma concentration, were determined following a single oral dose of pantoprazole |
| Time to Peak Concentration (Tmax) Profile | 1 day | Pharmacokinetic (PK) parameters, including time to peak plasma concentration, were determined following a single oral dose of pantoprazole. |
| Disposition Half-life | 1 day | 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. |
| Area Under the Concentration-time Curve (AUC) | 1 day | 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. |
| Apparent Oral Clearance (CL/F) | 1 day | 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. |
| Pantoprazole Plasma Concentration After Multiple-Dose Oral Administration | 7 days | Plasma concentration of pantoprazole after multiple doses was measured to see if there was any accumulation of the drug. |
| Intragastric pH | 7 days | 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). |
| Median Intragastric pH | 7 days | 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). |
| Percentage of Time Intragastric pH Was >4 | 7 days | 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). |
| Mean Intraesophageal pH | 7 days | 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). |
| Median Intraesophageal pH | 7 days | 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). |
| Percentage of Time That Intraesophageal pH Was <4 | 7 days | 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). |
| Normalized Area of Gastric Hydrogen Ion Activity Over Time | 7 days | 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. |
| Normalized Area of Esophageal Hydrogen Ion Activity Over Time | 7 days | 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. |
Countries
Australia, Belgium, France, Germany, Italy, Poland, Switzerland, United States
Participant flow
Recruitment details
Patients were recruited February 2006 to January 2008.
Pre-assignment details
Patients were screened for seven days.
Participants by arm
| Arm | Count |
|---|---|
| Low Dose Pantoprazole (0.6 mg/kg) Patients weighing 2.5 to \<7 kg received pantoprazole sodium enteric-coated spheroid suspension daily 2.5 mg. Patients weighing ≥7 to ≤15 kg received pantoprazole sodium enteric-coated spheroid suspension daily 5 mg. This dosing corresponds to approximately 0.6 mg/kg. | 33 |
| High Dose Pantoprazole (1.2 mg/kg) Patients weighing 2.5 to \<7 kg received pantoprazole sodium enteric-coated spheroid suspension daily 5 mg. Patients weighing ≥7 to ≤15 kg received pantoprazole sodium enteric-coated spheroid suspension daily 10 mg. This dosing corresponds to approximately 1.2 mg/kg. | 34 |
| Total | 67 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Low Dose Pantoprazole (0.6 mg/kg) | High Dose Pantoprazole (1.2 mg/kg) | Total |
|---|---|---|---|
| Age Continuous | 5.98 months STANDARD_DEVIATION 2.98 | 5.91 months STANDARD_DEVIATION 3.42 | 5.94 months STANDARD_DEVIATION 3.19 |
| Sex: Female, Male Female | 13 Participants | 15 Participants | 28.0 Participants |
| Sex: Female, Male Male | 20 Participants | 19 Participants | 39.0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / — | 17 / — |
| serious Total, serious adverse events | 3 / — | 2 / — |
Outcome results
Primary
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.
Time frame: 1 day
Population: All patients without any major protocol violations who received 1 dose of pantoprazole on the day the PK samples were obtained, who had at least 4 blood samples, and for whom the pantoprazole terminal-phase disposition half-life could be estimated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose Pantoprazole (0.6 mg/kg) | Apparent Oral Clearance (CL/F) | 1.54 L/hr/kg | Standard Deviation 2.35 |
| High Dose Pantoprazole (1.2 mg/kg) | Apparent Oral Clearance (CL/F) | 0.87 L/hr/kg | Standard Deviation 1.36 |
Primary
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.
Time frame: 1 day
Population: All patients without any major protocol violations who received 1 dose of pantoprazole on the day the PK samples were obtained, who had at least 4 blood samples, and for whom the pantoprazole terminal-phase disposition half-life could be estimated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose Pantoprazole (0.6 mg/kg) | Area Under the Concentration-time Curve (AUC) | 1046 ng*hr/mL | Standard Deviation 1043 |
| High Dose Pantoprazole (1.2 mg/kg) | Area Under the Concentration-time Curve (AUC) | 3602 ng*hr/mL | Standard Deviation 3269 |
Primary
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.
Time frame: 1 day
Population: All patients without any major protocol violations who received 1 dose of pantoprazole on the day the PK samples were obtained, who had at least 4 blood samples, and for whom the pantoprazole terminal-phase disposition half-life could be estimated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose Pantoprazole (0.6 mg/kg) | Disposition Half-life | 1.78 hr | Standard Deviation 1.3 |
| High Dose Pantoprazole (1.2 mg/kg) | Disposition Half-life | 1.42 hr | Standard Deviation 0.78 |
Primary
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).
Time frame: 7 days
Population: Patients who had baseline and steady-state pH-metry performed, total pH-metry recording time of at least 16 hours, and received at least 5 consecutive daily doses of pantoprazole before the steady-state pH-metry was performed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Pantoprazole (0.6 mg/kg) | Intragastric pH | Baseline | 4.2 units on scale | Standard Deviation 1.4 |
| Low Dose Pantoprazole (0.6 mg/kg) | Intragastric pH | Steady state | 4.8 units on scale | Standard Deviation 1.3 |
| High Dose Pantoprazole (1.2 mg/kg) | Intragastric pH | Baseline | 3.0 units on scale | Standard Deviation 1.4 |
| High Dose Pantoprazole (1.2 mg/kg) | Intragastric pH | Steady state | 4.2 units on scale | Standard Deviation 1.5 |
Comparison: Within group comparison between steady state and baselinep-value: 0.087t-test, 2 sided
Comparison: Within group comparison between steady state and baselinep-value: 0.019t-test, 2 sided
Primary
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).
Time frame: 7 days
Population: Patients who had baseline and steady-state pH-metry performed, total pH-metry recording time of at least 16 hours, and received at least 5 consecutive daily doses of pantoprazole before the steady-state pH-metry was performed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Pantoprazole (0.6 mg/kg) | Mean Intraesophageal pH | Baseline | 5.7 units on scale | Standard Deviation 0.7 |
| Low Dose Pantoprazole (0.6 mg/kg) | Mean Intraesophageal pH | Steady state | 5.6 units on scale | Standard Deviation 0.8 |
| High Dose Pantoprazole (1.2 mg/kg) | Mean Intraesophageal pH | Steady state | 4.9 units on scale | Standard Deviation 0.3 |
| High Dose Pantoprazole (1.2 mg/kg) | Mean Intraesophageal pH | Baseline | 5.2 units on scale | Standard Deviation 0.4 |
Comparison: Within group comparison between steady state and baselinep-value: 0.347t-test, 2 sided
Comparison: Within group comparison between steady state and baselinep-value: 0.012t-test, 2 sided
Primary
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).
Time frame: 7 days
Population: Patients who had baseline and steady-state pH-metry performed, total pH-metry recording time of at least 16 hours, and received at least 5 consecutive daily doses of pantoprazole before the steady-state pH-metry was performed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Pantoprazole (0.6 mg/kg) | Median Intraesophageal pH | Baseline | 5.8 units on scale | Standard Deviation 0.7 |
| Low Dose Pantoprazole (0.6 mg/kg) | Median Intraesophageal pH | Steady state | 5.6 units on scale | Standard Deviation 0.8 |
| High Dose Pantoprazole (1.2 mg/kg) | Median Intraesophageal pH | Baseline | 5.3 units on scale | Standard Deviation 0.5 |
| High Dose Pantoprazole (1.2 mg/kg) | Median Intraesophageal pH | Steady state | 4.9 units on scale | Standard Deviation 0.4 |
Comparison: Within group comparison between steady state and baselinep-value: 0.339t-test, 2 sided
Comparison: Within group comparison between steady state and baselinep-value: 0.003t-test, 2 sided
Primary
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).
Time frame: 7 days
Population: Patients who had baseline and steady-state pH-metry performed, total pH-metry recording time of at least 16 hours, and received at least 5 consecutive daily doses of pantoprazole before the steady-state pH-metry was performed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Pantoprazole (0.6 mg/kg) | Median Intragastric pH | Baseline | 4.2 units on scale | Standard Deviation 1.7 |
| Low Dose Pantoprazole (0.6 mg/kg) | Median Intragastric pH | Steady state | 4.7 units on scale | Standard Deviation 1.7 |
| High Dose Pantoprazole (1.2 mg/kg) | Median Intragastric pH | Baseline | 2.8 units on scale | Standard Deviation 1.5 |
| High Dose Pantoprazole (1.2 mg/kg) | Median Intragastric pH | Steady state | 4.2 units on scale | Standard Deviation 1.9 |
Comparison: Within group comparison between steady state and baselinep-value: 0.255t-test, 2 sided
Comparison: Within group comparison between steady state and baseline.p-value: 0.031t-test, 2 sided
Primary
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.
Time frame: 7 days
Population: Patients who had baseline and steady-state pH-metry performed, total pH-metry recording time of at least 16 hours, and received at least 5 consecutive daily doses of pantoprazole before the steady-state pH-metry was performed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Pantoprazole (0.6 mg/kg) | Normalized Area of Esophageal Hydrogen Ion Activity Over Time | Baseline | 2.1 H*mmol/L | Standard Deviation 1.6 |
| Low Dose Pantoprazole (0.6 mg/kg) | Normalized Area of Esophageal Hydrogen Ion Activity Over Time | Steady state | 1.5 H*mmol/L | Standard Deviation 2.4 |
| High Dose Pantoprazole (1.2 mg/kg) | Normalized Area of Esophageal Hydrogen Ion Activity Over Time | Baseline | 3.5 H*mmol/L | Standard Deviation 2.3 |
| High Dose Pantoprazole (1.2 mg/kg) | Normalized Area of Esophageal Hydrogen Ion Activity Over Time | Steady state | 1.5 H*mmol/L | Standard Deviation 0.6 |
Comparison: Within group comparison between steady state and baselinep-value: 0.387t-test, 2 sided
Comparison: Within group comparison between steady state and baselinep-value: 0.021t-test, 2 sided
Primary
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.
Time frame: 7 days
Population: Patients who had baseline and steady-state pH-metry performed, total pH-metry recording time of at least 16 hours, and received at least 5 consecutive daily doses of pantoprazole before the steady-state pH-metry was performed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Pantoprazole (0.6 mg/kg) | Normalized Area of Gastric Hydrogen Ion Activity Over Time | Baseline | 259.7 H*mmol/L | Standard Deviation 442.7 |
| Low Dose Pantoprazole (0.6 mg/kg) | Normalized Area of Gastric Hydrogen Ion Activity Over Time | Steady state | 102.3 H*mmol/L | Standard Deviation 118.6 |
| High Dose Pantoprazole (1.2 mg/kg) | Normalized Area of Gastric Hydrogen Ion Activity Over Time | Baseline | 921.0 H*mmol/L | Standard Deviation 1290.1 |
| High Dose Pantoprazole (1.2 mg/kg) | Normalized Area of Gastric Hydrogen Ion Activity Over Time | Steady state | 303.6 H*mmol/L | Standard Deviation 524.9 |
Comparison: Within group comparison between steady state and baselinep-value: 0.166t-test, 2 sided
Comparison: Within group comparison between steady state and baselinep-value: 0.119t-test, 2 sided
Primary
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.
Time frame: 7 days
Population: All patients for whom at least 2 PK samples were obtained after 5 consecutive doses. Low dose population was 19 for both 2 and 4 hours. High dose population was 17 and 18 for 2 and 4 hours respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Pantoprazole (0.6 mg/kg) | Pantoprazole Plasma Concentration After Multiple-Dose Oral Administration | 4 hours | 69 ng/mL | Standard Deviation 102 |
| Low Dose Pantoprazole (0.6 mg/kg) | Pantoprazole Plasma Concentration After Multiple-Dose Oral Administration | 2 hours | 289 ng/mL | Standard Deviation 354 |
| High Dose Pantoprazole (1.2 mg/kg) | Pantoprazole Plasma Concentration After Multiple-Dose Oral Administration | 4 hours | 353 ng/mL | Standard Deviation 509 |
| High Dose Pantoprazole (1.2 mg/kg) | Pantoprazole Plasma Concentration After Multiple-Dose Oral Administration | 2 hours | 668 ng/mL | Standard Deviation 825 |
Primary
Peak Concentration (Cmax)
Pharmacokinetic (PK) parameters, including peak plasma concentration, were determined following a single oral dose of pantoprazole
Time frame: 1 day
Population: All patients without any major protocol violations who received 1 dose of pantoprazole on the day the PK samples were obtained, who had at least 4 blood samples, and for whom the pantoprazole terminal-phase disposition half-life could be estimated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose Pantoprazole (0.6 mg/kg) | Peak Concentration (Cmax) | 567 ng/mL | Standard Deviation 534 |
| High Dose Pantoprazole (1.2 mg/kg) | Peak Concentration (Cmax) | 1527 ng/mL | Standard Deviation 1298 |
Primary
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).
Time frame: 7 days
Population: Patients who had baseline and steady-state pH-metry performed, total pH-metry recording time of at least 16 hours, and received at least 5 consecutive daily doses of pantoprazole before the steady-state pH-metry was performed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Pantoprazole (0.6 mg/kg) | Percentage of Time Intragastric pH Was >4 | Baseline | 55.5 percentage of time | Standard Deviation 28.6 |
| Low Dose Pantoprazole (0.6 mg/kg) | Percentage of Time Intragastric pH Was >4 | Steady state | 68.5 percentage of time | Standard Deviation 28.3 |
| High Dose Pantoprazole (1.2 mg/kg) | Percentage of Time Intragastric pH Was >4 | Baseline | 32.2 percentage of time | Standard Deviation 24.1 |
| High Dose Pantoprazole (1.2 mg/kg) | Percentage of Time Intragastric pH Was >4 | Steady state | 56.6 percentage of time | Standard Deviation 31.1 |
Comparison: Within group comparison between steady state and baselinep-value: 0.099t-test, 2 sided
Comparison: Within group comparison between steady state and baselinep-value: 0.016t-test, 2 sided
Primary
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).
Time frame: 7 days
Population: Patients who had baseline and steady-state pH-metry performed, total pH-metry recording time of at least 16 hours, and received at least 5 consecutive daily doses of pantoprazole before the steady-state pH-metry was performed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Pantoprazole (0.6 mg/kg) | Percentage of Time That Intraesophageal pH Was <4 | Baseline | 4.6 percentage of time | Standard Deviation 3.9 |
| Low Dose Pantoprazole (0.6 mg/kg) | Percentage of Time That Intraesophageal pH Was <4 | Steady state | 4.6 percentage of time | Standard Deviation 5.6 |
| High Dose Pantoprazole (1.2 mg/kg) | Percentage of Time That Intraesophageal pH Was <4 | Steady state | 9.4 percentage of time | Standard Deviation 5.8 |
| High Dose Pantoprazole (1.2 mg/kg) | Percentage of Time That Intraesophageal pH Was <4 | Baseline | 8.0 percentage of time | Standard Deviation 5.6 |
Comparison: Within group comparison between steady state and baselinep-value: 0.982t-test, 2 sided
Comparison: Within group comparison between steady state and baselinep-value: 0.534t-test, 2 sided
Primary
Time to Peak Concentration (Tmax) Profile
Pharmacokinetic (PK) parameters, including time to peak plasma concentration, were determined following a single oral dose of pantoprazole.
Time frame: 1 day
Population: All patients without any major protocol violations who received 1 dose of pantoprazole on the day the PK samples were obtained, who had at least 4 blood samples, and for whom the pantoprazole terminal-phase disposition half-life could be estimated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low Dose Pantoprazole (0.6 mg/kg) | Time to Peak Concentration (Tmax) Profile | 1.03 hr |
| High Dose Pantoprazole (1.2 mg/kg) | Time to Peak Concentration (Tmax) Profile | 1.02 hr |