Gastroesophageal Reflux
Conditions
Keywords
Safety
Brief summary
The purpose of this study is to determine whether or not consistent drug levels can be achieved in infants with presumed Gastroesophageal Reflux Disease.
Interventions
DRUGpantoprazole
Sponsors
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 Days to 28 Days
Healthy volunteers
No
Inclusion criteria
* Hospitalized patients * Presumed diagnosis of GERD * Term or post-term infants within the neonatal period less than 28 days or preterm infants with a corrected gestational age of less than 44 weeks
Exclusion criteria
* cardiovascular instability * clinically significant laboratory abnormalities * use of warfarin, carbamazepine, phenytoin, or rifampin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Variance of Oral Bioavailability | 1 day | Samples were divided between 2 groups for each dose: Group A at baseline, 2, 8, 18 hours; Group B at baseline, 1, 4, 12 hours to reduce the number of blood draws per infant. The variance of oral bioavailability was assessed to determine if further PK assessment was appropriate. It would be considered highly variable if the square root of the sum of the standard deviation squares of the area under the concentration-time curves from time zero to the time of the last quantifiable concentration (AUCT) for group A and Group B divided by the sum of the mean AUCT for group A and Group B was \>1.2. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve (AUC) | Baseline to 24 hours post dose on Day 1 | AUC is a measure of the plasma concentration of the drug over time. It is used to characterize drug absorption. AUC was estimated from population pharmacokinetic (PK) modeling. |
| Apparent Oral Clearance (Cl/F) | 1 day | 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. |
| Half Life | 1 day | Half life is the time required for half the quantity of absorbed drug to be metabolized or eliminated by normal biological processes. Half life was estimated from population pharmacokinetic (PK) modeling. |
Countries
Australia, Belgium, Canada, France, Germany, Italy, Netherlands, Poland, South Africa, Switzerland, United States
Participant flow
Recruitment details
Patients were recruited in multiple countries worldwide from July 2006 to December 2007.
Pre-assignment details
Patients were screened for up to 5 days.
Participants by arm
| Arm | Count |
|---|---|
| 1.25 mg Pantoprazole 1.25 mg of pantoprazole granules daily for at least 5 days. This dosing corresponds to approximately 0.6 mg/kg | 19 |
| 2.5 mg Pantoprazole 2.5 mg of pantoprazole granules daily for at least 5 days. This dose corresponds to approximately 1.2 mg/kg | 40 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | 1.25 mg Pantoprazole | 2.5 mg Pantoprazole | Total |
|---|---|---|---|
| Age Continuous | 8.63 weeks (postnatal age) STANDARD_DEVIATION 4.86 | 7.70 weeks (postnatal age) STANDARD_DEVIATION 4.2 | 8.00 weeks (postnatal age) STANDARD_DEVIATION 4.4 |
| Sex: Female, Male Female | 5 Participants | 13 Participants | 18 Participants |
| Sex: Female, Male Male | 14 Participants | 27 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / — | 18 / — |
| serious Total, serious adverse events | 0 / — | 2 / — |
Outcome results
Primary
Variance of Oral Bioavailability
Samples were divided between 2 groups for each dose: Group A at baseline, 2, 8, 18 hours; Group B at baseline, 1, 4, 12 hours to reduce the number of blood draws per infant. The variance of oral bioavailability was assessed to determine if further PK assessment was appropriate. It would be considered highly variable if the square root of the sum of the standard deviation squares of the area under the concentration-time curves from time zero to the time of the last quantifiable concentration (AUCT) for group A and Group B divided by the sum of the mean AUCT for group A and Group B was \>1.2.
Time frame: 1 day
Population: Single dose PK Valid-For Efficacy patients (defined as those without any major protocol violations who completed the single-dose PK determinations and taken the test article on the date the PK samples were taken). 2 poor metabolizers were excluded from this analysis.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| 1.25 mg Pantoprazole | Variance of Oral Bioavailability | 1.07 ratio | 2.59 |
| 2.5 mg Pantoprazole | Variance of Oral Bioavailability | 0.74 ratio | 2.29 |
Secondary
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.
Time frame: 1 day
Population: Single dose PK Valid-For-Efficacy patients (defined as those without any major protocol violations who completed the single-dose PK determinations and took the test article on the date the PK samples were taken) who also had measurable concentrations over the period of observation. 2 poor metabolizers were excluded from this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1.25 mg Pantoprazole | Apparent Oral Clearance (Cl/F) | 0.21 L/hr/kg | Standard Deviation 0.12 |
| 2.5 mg Pantoprazole | Apparent Oral Clearance (Cl/F) | 0.23 L/hr/kg | Standard Deviation 0.21 |
Secondary
Area Under the Concentration-time Curve (AUC)
AUC is a measure of the plasma concentration of the drug over time. It is used to characterize drug absorption. AUC was estimated from population pharmacokinetic (PK) modeling.
Time frame: Baseline to 24 hours post dose on Day 1
Population: Single dose PK Valid-For-Efficacy patients (defined as those without any major protocol violations who completed the single-dose PK determinations and took the test article on the date the PK samples were taken) who also had measurable concentrations over the period of observation. 2 poor metabolizers were excluded from this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1.25 mg Pantoprazole | Area Under the Concentration-time Curve (AUC) | 3540 ng*hr/mL | Standard Deviation 2820 |
| 2.5 mg Pantoprazole | Area Under the Concentration-time Curve (AUC) | 7270 ng*hr/mL | Standard Deviation 5304 |
Secondary
Half Life
Half life is the time required for half the quantity of absorbed drug to be metabolized or eliminated by normal biological processes. Half life was estimated from population pharmacokinetic (PK) modeling.
Time frame: 1 day
Population: Single dose PK Valid-For-Efficacy patients (defined as those without any major protocol violations who completed the single-dose PK determinations and took the test article on the date the PK samples were taken) who also had measurable concentrations over the period of observation. 2 poor metabolizers were excluded from this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1.25 mg Pantoprazole | Half Life | 3.1 hours | Standard Deviation 1.5 |
| 2.5 mg Pantoprazole | Half Life | 2.7 hours | Standard Deviation 1.1 |