Gastroesophageal Reflux
Conditions
Keywords
Gastrointestinal Reflux Disease
Brief summary
The purpose of this study is to characterize the PK profile, safety and tolerability of single and multiple doses of pantoprazole in children aged 1 through 11 years with endoscopically proven GERD.
Interventions
DRUGpantoprazole for approximately 9 weeks.
Sponsors
Wyeth is now a wholly owned subsidiary of Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
* Endoscopically proven GERD diagnosed within 6 months before study entry. * Weight must be equal to or over 8.3 kg; for subjects 6 years or greater, weight must be equal to or under 25 kg
Exclusion criteria
* History of GI disorders, ie, unrepaired tracheal esophageal fistula, GI malabsorption, Eosinophilic esophagitis * Subjects 6-11 years old unable to swallow tablets
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) | Predose (0 hour), and 0.5, 1, 2, 4, 6, 12 hours postdose | — |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | Predose (0 hour), and 0.5, 1, 2, 4, 6, 12 hours postdose | — |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] | Predose (0 hour), and 0.5, 1, 2, 4, 6, 12 hours postdose | AUC (0-t)= Area under the plasma concentration versus time curve from time zero (predose) to time of last quantifiable concentration (0-t). |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] | Predose (0 hour), and 0.5, 1, 2, 4, 6, 12 hours postdose | AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (predose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). |
| Plasma Decay Half-Life (t1/2) | Predose (0 hour), and 0.5, 1, 2, 4, 6, 12 hours postdose | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
| Apparent Oral Clearance (CL/F) | Predose (0 hour), and 0.5, 1, 2, 4, 6, 12 hours postdose | 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. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. |
| Terminal-Phase Volume of Distribution (Vz/F) | Predose (0 hour), and 0.5, 1, 2, 4, 6, 12 hours postdose | Vz/F was calculated as the ratio of clearance (CL) to terminal disposition rate constant (λz). |
| Plasma Concentrations After Multiple Doses | Hours 2 and 4 on Day 7 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pantoprazole 0.6 mg/kg Spheroids Pantoprazole 0.6 mg/kg Spheroids for Participants Aged \<6 years | 7 |
| Pantoprazole 1.2 mg/kg Spheroids Pantoprazole 1.2 mg/kg Spheroids for Participants Aged \<6 years | 10 |
| Pantoprazole 0.6 mg/kg Tablets Pantoprazole 0.6 mg/kg Tablets for Participants Aged \>=6 years | 11 |
| Pantoprazole 1.2 mg/kg Tablets Pantoprazole 1.2 mg/kg Tablets for Participants Aged \>=6 years | 13 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Parent request | 1 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Pantoprazole 0.6 mg/kg Spheroids | Pantoprazole 1.2 mg/kg Spheroids | Pantoprazole 0.6 mg/kg Tablets | Pantoprazole 1.2 mg/kg Tablets | Total |
|---|---|---|---|---|---|
| Age Continuous | 3.86 years STANDARD_DEVIATION 1.46 | 2.80 years STANDARD_DEVIATION 1.55 | 8.55 years STANDARD_DEVIATION 1.97 | 8.77 years STANDARD_DEVIATION 1.09 | 6.41 years STANDARD_DEVIATION 3.11 |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 4 Participants | 6 Participants | 16 Participants |
| Sex: Female, Male Male | 5 Participants | 6 Participants | 7 Participants | 7 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 7 | 7 / 10 | 9 / 11 | 7 / 13 |
| serious Total, serious adverse events | 0 / 7 | 0 / 10 | 0 / 11 | 0 / 13 |
Outcome results
Primary
Apparent Oral Clearance (CL/F)
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. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time frame: Predose (0 hour), and 0.5, 1, 2, 4, 6, 12 hours postdose
Population: Single-Dose Valid-for-Evaluation Population. Participants analyzed=number of participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pantoprazole 0.6 mg/kg Spheroids | Apparent Oral Clearance (CL/F) | 2.08 liter per hour per kilogram (L/h/kg) | Standard Deviation 1.27 |
| Pantoprazole 1.2 mg/kg Spheroids | Apparent Oral Clearance (CL/F) | 1.28 liter per hour per kilogram (L/h/kg) | Standard Deviation 1.16 |
| Pantoprazole 0.6 mg/kg Tablets | Apparent Oral Clearance (CL/F) | 0.41 liter per hour per kilogram (L/h/kg) | Standard Deviation 0.3 |
| Pantoprazole 1.2 mg/kg Tablets | Apparent Oral Clearance (CL/F) | 0.40 liter per hour per kilogram (L/h/kg) | Standard Deviation 0.22 |
Primary
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]
AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (predose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).
Time frame: Predose (0 hour), and 0.5, 1, 2, 4, 6, 12 hours postdose
Population: Single-Dose Valid-for-Evaluation Population. Participants analyzed=number of participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pantoprazole 0.6 mg/kg Spheroids | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] | 293.29 ng*h/mL | Standard Deviation 146.41 |
| Pantoprazole 1.2 mg/kg Spheroids | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] | 2448.08 ng*h/mL | Standard Deviation 2170.48 |
| Pantoprazole 0.6 mg/kg Tablets | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] | 2497.13 ng*h/mL | Standard Deviation 2099.64 |
| Pantoprazole 1.2 mg/kg Tablets | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] | 3782.49 ng*h/mL | Standard Deviation 1837.42 |
Primary
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]
AUC (0-t)= Area under the plasma concentration versus time curve from time zero (predose) to time of last quantifiable concentration (0-t).
Time frame: Predose (0 hour), and 0.5, 1, 2, 4, 6, 12 hours postdose
Population: Single-Dose Valid-for-Evaluation Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pantoprazole 0.6 mg/kg Spheroids | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] | 208.96 nanogram hour per milliliter (ng*h/mL) | Standard Deviation 197.54 |
| Pantoprazole 1.2 mg/kg Spheroids | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] | 2273.96 nanogram hour per milliliter (ng*h/mL) | Standard Deviation 1885.68 |
| Pantoprazole 0.6 mg/kg Tablets | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] | 2448.61 nanogram hour per milliliter (ng*h/mL) | Standard Deviation 2007.21 |
| Pantoprazole 1.2 mg/kg Tablets | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] | 3190.96 nanogram hour per milliliter (ng*h/mL) | Standard Deviation 2137.91 |
Primary
Maximum Observed Plasma Concentration (Cmax)
Time frame: Predose (0 hour), and 0.5, 1, 2, 4, 6, 12 hours postdose
Population: Single-Dose Valid-for-Evaluation Population: Randomized participants who took 1 dose of pantoprazole and had at least 4 single-dose blood samples for pharmacokinetic (PK) analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pantoprazole 0.6 mg/kg Spheroids | Maximum Observed Plasma Concentration (Cmax) | 136 nanogram per milliliter (ng/mL) | Standard Deviation 127 |
| Pantoprazole 1.2 mg/kg Spheroids | Maximum Observed Plasma Concentration (Cmax) | 798 nanogram per milliliter (ng/mL) | Standard Deviation 729 |
| Pantoprazole 0.6 mg/kg Tablets | Maximum Observed Plasma Concentration (Cmax) | 1643 nanogram per milliliter (ng/mL) | Standard Deviation 1229 |
| Pantoprazole 1.2 mg/kg Tablets | Maximum Observed Plasma Concentration (Cmax) | 2067 nanogram per milliliter (ng/mL) | Standard Deviation 1320 |
Primary
Plasma Concentrations After Multiple Doses
Time frame: Hours 2 and 4 on Day 7
Population: Multiple-Dose Valid-for-Evaluation Population: Randomized participants who had concentration evaluations of pantoprazole either at 2 hours or at 4 hours after single dose and after at least 5 consecutive doses. n=participants who had data available at that specific time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pantoprazole 0.6 mg/kg Spheroids | Plasma Concentrations After Multiple Doses | Hour 2 on Day 7 (n=5, 8, 10, 13) | 212.30 ng/mL | Standard Deviation 222.08 |
| Pantoprazole 0.6 mg/kg Spheroids | Plasma Concentrations After Multiple Doses | Hour 4 on Day 7 (n=6, 8, 10, 13) | 503.25 ng/mL | Standard Deviation 1087.91 |
| Pantoprazole 1.2 mg/kg Spheroids | Plasma Concentrations After Multiple Doses | Hour 4 on Day 7 (n=6, 8, 10, 13) | 207.23 ng/mL | Standard Deviation 211.92 |
| Pantoprazole 1.2 mg/kg Spheroids | Plasma Concentrations After Multiple Doses | Hour 2 on Day 7 (n=5, 8, 10, 13) | 486.49 ng/mL | Standard Deviation 605.22 |
| Pantoprazole 0.6 mg/kg Tablets | Plasma Concentrations After Multiple Doses | Hour 4 on Day 7 (n=6, 8, 10, 13) | 123.83 ng/mL | Standard Deviation 163.78 |
| Pantoprazole 0.6 mg/kg Tablets | Plasma Concentrations After Multiple Doses | Hour 2 on Day 7 (n=5, 8, 10, 13) | 592.32 ng/mL | Standard Deviation 914.57 |
| Pantoprazole 1.2 mg/kg Tablets | Plasma Concentrations After Multiple Doses | Hour 2 on Day 7 (n=5, 8, 10, 13) | 2337.89 ng/mL | Standard Deviation 1817.78 |
| Pantoprazole 1.2 mg/kg Tablets | Plasma Concentrations After Multiple Doses | Hour 4 on Day 7 (n=6, 8, 10, 13) | 200.78 ng/mL | Standard Deviation 209.81 |
Primary
Plasma Decay Half-Life (t1/2)
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: Predose (0 hour), and 0.5, 1, 2, 4, 6, 12 hours postdose
Population: Single-Dose Valid-for-Evaluation Population. Participants analyzed=number of participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pantoprazole 0.6 mg/kg Spheroids | Plasma Decay Half-Life (t1/2) | 5.34 hours | Standard Deviation 7.39 |
| Pantoprazole 1.2 mg/kg Spheroids | Plasma Decay Half-Life (t1/2) | 1.68 hours | Standard Deviation 0.64 |
| Pantoprazole 0.6 mg/kg Tablets | Plasma Decay Half-Life (t1/2) | 0.77 hours | Standard Deviation 0.22 |
| Pantoprazole 1.2 mg/kg Tablets | Plasma Decay Half-Life (t1/2) | 0.70 hours | Standard Deviation 0.16 |
Primary
Terminal-Phase Volume of Distribution (Vz/F)
Vz/F was calculated as the ratio of clearance (CL) to terminal disposition rate constant (λz).
Time frame: Predose (0 hour), and 0.5, 1, 2, 4, 6, 12 hours postdose
Population: Single-Dose Valid-for-Evaluation Population. Participants analyzed=number of participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pantoprazole 0.6 mg/kg Spheroids | Terminal-Phase Volume of Distribution (Vz/F) | 12.22 liter per kilogram (L/kg) | Standard Deviation 14.68 |
| Pantoprazole 1.2 mg/kg Spheroids | Terminal-Phase Volume of Distribution (Vz/F) | 2.89 liter per kilogram (L/kg) | Standard Deviation 2.92 |
| Pantoprazole 0.6 mg/kg Tablets | Terminal-Phase Volume of Distribution (Vz/F) | 0.43 liter per kilogram (L/kg) | Standard Deviation 0.3 |
| Pantoprazole 1.2 mg/kg Tablets | Terminal-Phase Volume of Distribution (Vz/F) | 0.40 liter per kilogram (L/kg) | Standard Deviation 0.27 |
Primary
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time frame: Predose (0 hour), and 0.5, 1, 2, 4, 6, 12 hours postdose
Population: Single-Dose Valid-for-Evaluation Population. Participants analyzed=number of participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pantoprazole 0.6 mg/kg Spheroids | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 1.45 hours | Standard Deviation 0.69 |
| Pantoprazole 1.2 mg/kg Spheroids | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 2.71 hours | Standard Deviation 1.25 |
| Pantoprazole 0.6 mg/kg Tablets | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 2.08 hours | Standard Deviation 0.75 |
| Pantoprazole 1.2 mg/kg Tablets | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 2.03 hours | Standard Deviation 0.74 |