Trial Outcomes & Findings for Study Evaluating Pantoprazole in Neonates and Preterm Infants With GERD (NCT NCT00362609)
NCT ID: NCT00362609
Last Updated: 2010-05-14
Results Overview
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.
COMPLETED
PHASE3
59 participants
1 day
2010-05-14
Participant Flow
Patients were recruited in multiple countries worldwide from July 2006 to December 2007.
Patients were screened for up to 5 days.
Participant milestones
| Measure |
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
|
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
|
|---|---|---|
|
Overall Study
STARTED
|
19
|
40
|
|
Overall Study
COMPLETED
|
19
|
38
|
|
Overall Study
NOT COMPLETED
|
0
|
2
|
Reasons for withdrawal
| Measure |
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
|
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
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
|
Overall Study
Protocol Violation
|
0
|
1
|
Baseline Characteristics
Study Evaluating Pantoprazole in Neonates and Preterm Infants With GERD
Baseline characteristics by cohort
| Measure |
1.25 mg Pantoprazole
n=19 Participants
1.25 mg of pantoprazole granules daily for at least 5 days. This dosing corresponds to approximately 0.6 mg/kg
|
2.5 mg Pantoprazole
n=40 Participants
2.5 mg of pantoprazole granules daily for at least 5 days. This dose corresponds to approximately 1.2 mg/kg
|
Total
n=59 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
8.63 weeks (postnatal age)
STANDARD_DEVIATION 4.86 • n=5 Participants
|
7.70 weeks (postnatal age)
STANDARD_DEVIATION 4.20 • n=7 Participants
|
8.00 weeks (postnatal age)
STANDARD_DEVIATION 4.40 • n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
41 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 1 dayPopulation: 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.
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.
Outcome measures
| Measure |
1.25 mg Pantoprazole
n=19 Participants
1.25 mg of pantoprazole granules daily for at least 5 days. This dosing corresponds to approximately 0.6 mg/kg
|
2.5 mg Pantoprazole
n=21 Participants
2.5 mg of pantoprazole granules daily for at least 5 days. This dose corresponds to approximately 1.2 mg/kg
|
|---|---|---|
|
Variance of Oral Bioavailability
|
1.07 ratio
2.59
|
0.74 ratio
2.29
|
SECONDARY outcome
Timeframe: Baseline to 24 hours post dose on Day 1Population: 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.
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.
Outcome measures
| Measure |
1.25 mg Pantoprazole
n=14 Participants
1.25 mg of pantoprazole granules daily for at least 5 days. This dosing corresponds to approximately 0.6 mg/kg
|
2.5 mg Pantoprazole
n=19 Participants
2.5 mg of pantoprazole granules daily for at least 5 days. This dose corresponds to approximately 1.2 mg/kg
|
|---|---|---|
|
Area Under the Concentration-time Curve (AUC)
|
3540 ng*hr/mL
Standard Deviation 2820
|
7270 ng*hr/mL
Standard Deviation 5304
|
SECONDARY outcome
Timeframe: 1 dayPopulation: 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.
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.
Outcome measures
| Measure |
1.25 mg Pantoprazole
n=14 Participants
1.25 mg of pantoprazole granules daily for at least 5 days. This dosing corresponds to approximately 0.6 mg/kg
|
2.5 mg Pantoprazole
n=19 Participants
2.5 mg of pantoprazole granules daily for at least 5 days. This dose corresponds to approximately 1.2 mg/kg
|
|---|---|---|
|
Apparent Oral Clearance (Cl/F)
|
0.21 L/hr/kg
Standard Deviation 0.12
|
0.23 L/hr/kg
Standard Deviation 0.21
|
SECONDARY outcome
Timeframe: 1 dayPopulation: 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.
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.
Outcome measures
| Measure |
1.25 mg Pantoprazole
n=14 Participants
1.25 mg of pantoprazole granules daily for at least 5 days. This dosing corresponds to approximately 0.6 mg/kg
|
2.5 mg Pantoprazole
n=19 Participants
2.5 mg of pantoprazole granules daily for at least 5 days. This dose corresponds to approximately 1.2 mg/kg
|
|---|---|---|
|
Half Life
|
3.1 hours
Standard Deviation 1.5
|
2.7 hours
Standard Deviation 1.1
|
Adverse Events
1.25 mg Pantoprazole
2.5 mg Pantoprazole
Serious adverse events
| Measure |
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
|
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
|
|---|---|---|
|
Renal and urinary disorders
Urinary Tract Infection
|
0.00%
0/19
|
2.5%
1/40
|
|
Gastrointestinal disorders
Gastrointestinal hemorrhage
|
0.00%
0/19
|
2.5%
1/40
|
Other adverse events
| Measure |
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
|
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
|
|---|---|---|
|
General disorders
Fever
|
0.00%
0/19
|
2.5%
1/40
|
|
General disorders
Hernia
|
0.00%
0/19
|
2.5%
1/40
|
|
Cardiac disorders
Bradycardia
|
5.3%
1/19
|
2.5%
1/40
|
|
Cardiac disorders
Cardiovascular physical finding
|
5.3%
1/19
|
0.00%
0/40
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/19
|
5.0%
2/40
|
|
Cardiac disorders
Ventricular extrasystoles
|
5.3%
1/19
|
0.00%
0/40
|
|
Gastrointestinal disorders
Constipation
|
5.3%
1/19
|
5.0%
2/40
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/19
|
2.5%
1/40
|
|
Gastrointestinal disorders
Liver function tests abnormal
|
0.00%
0/19
|
2.5%
1/40
|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/19
|
12.5%
5/40
|
|
Blood and lymphatic system disorders
Iron deficiency anemia
|
0.00%
0/19
|
2.5%
1/40
|
|
Metabolism and nutrition disorders
Peripheral edema
|
0.00%
0/19
|
2.5%
1/40
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal anomaly
|
5.3%
1/19
|
0.00%
0/40
|
|
Musculoskeletal and connective tissue disorders
Osteopenia
|
5.3%
1/19
|
0.00%
0/40
|
|
Respiratory, thoracic and mediastinal disorders
Apnea
|
5.3%
1/19
|
0.00%
0/40
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
5.3%
1/19
|
7.5%
3/40
|
|
Respiratory, thoracic and mediastinal disorders
Lung disorder
|
0.00%
0/19
|
2.5%
1/40
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary physical finding
|
5.3%
1/19
|
0.00%
0/40
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis
|
5.3%
1/19
|
5.0%
2/40
|
|
Skin and subcutaneous tissue disorders
Application site reaction
|
0.00%
0/19
|
2.5%
1/40
|
|
Skin and subcutaneous tissue disorders
Contact dermatitis
|
10.5%
2/19
|
0.00%
0/40
|
|
Eye disorders
Conjunctivitis
|
5.3%
1/19
|
0.00%
0/40
|
|
Eye disorders
Retinal disorder
|
5.3%
1/19
|
2.5%
1/40
|
|
Renal and urinary disorders
Urinary tract infection
|
0.00%
0/19
|
2.5%
1/40
|
|
Renal and urinary disorders
Urine abnormality
|
5.3%
1/19
|
0.00%
0/40
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The PIs agreed to allow the sponsor 60 days to review and require changes to presentations or publications but only to protect confidential information and intellectual property, and for the sponsor to file a patent application, as applicable. The PIs also agreed for data to be presented first as a joint, multi-center publication.
- Publication restrictions are in place
Restriction type: OTHER