Primary: To determine whether or not consistent exposures can be achieved in neonates and preterm infants with presumed GERD receiving oral doses of pantoprazole. Secondary: PK and PD assessment after single dose and steady state. Determination fo…
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Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
PK : The single-dose concentration versus time data will be analyzed initially
for the areas under the concentration versus time curves from time 0 to the
time T, at which time the last measurable concentration is obtained, for
patients from Group A (AUCT,A) and Group B (AUCT,B).
Concentrations of pantoprazole obtained following at least 5 consecutive doses
of pantoprazole will be summarized using descriptive statistics, while the
limited comparison of concentrations at 3 and 6 hours between the first and the
last doses may be made for the assessment of drug accumulation following
repeated dose administration.
PD Analyses: On each of the pH-metry days the following data will be collected
on the eCRF
· Mean and median intraesophageal pH
· Mean and median intragastric pH
· Percentage of time intragastric pH >4
· Percentage of time intragastric pH >3
· Percentage of time esophageal pH <4 (reflux index)
· Number of reflux episodes
· Number of episodes > 5 minutes
· Duration of longest episode
· AUC of gastric H+ concentration over time
Secondary outcome
GERD and respiratory symptoms will be collected at baseline and daily
throughout the study based upon nursing observations on a worksheet
Buccal cells for pharmacogenomic (PG) analysis of cytochrome P450 (CYP) enzymes
and CYP2C19 and CYP3A4 phenotypes will be collected with the parents/legal
guardian*s (PARENT) permission before the patient completes the study.
Background summary
Acid suppression therapy is being widely used in neonates and preterm infants
to treat various conditions, including the prevention or treatment of upper
gastrointestinal (GI) bleeding, and gastroesophageal reflux disease (GERD)
among other indications. However, no specific pantoprazole pharmacokinetic
(PK), pharmacodynamic (PD), clinical symptoms, safety, or dose information is
available in neonates and preterm infants. This study is designed to determine
the single- and multiple-dose PK, pharmacodynamic profile, change in clinical
symptoms, and safety of pantoprazole delayed-release granules administered as a
suspension in neonates and preterm infants with a clinical indication for acid
suppression to treat a presumptive diagnosis of GERD.
Study objective
Primary: To determine whether or not consistent exposures can be achieved in
neonates and preterm infants with presumed GERD receiving oral doses of
pantoprazole.
Secondary: PK and PD assessment after single dose and steady state.
Determination fo Gerd and respiratory symptoms. Safety evaluation.
Study design
This is a multicenter, open-label, randomized, single- and multiple-dose study
that will assess PK, clinical GERD and respiratory symptoms and safety of 2
dose levels of pantoprazole (1.25 mg and 2.5 mg) and the PD at one dose level
(2.5 mg) in neonates and preterm infants with a clinical indication for acid
suppression to treat a presumptive diagnosis of GERD. At least 6 days of
treatment. A follow-up contact day 23 ± 5 (approximately 15 ± 3 days after the
last dose of test article) or possibility to enroll in study 3001B3-335-WW
(open-label safety study with 6 weeks treatment).
Intervention
Single-dose PK Profiling: Each patient will have four blood samples (0.25
mL/sample) drawn.
Multiple-dose PK Profiling: Two multiple-dose (steady-state) PK samples
collected at 3 and 6 hours after administration of the final dose of test
article.
pH-metry: LES location may be verified by an LES Locator: fluoroscopy, x-ray,
or by calculation based upon Strobel*s formula in infants over 40 cm in
length.
Multiple-dose PD assessment:First on screening/baseline, second on study day 6,
approximately 1 hour before the final dose of test article, the pH probe will
be inserted. pH-metry during 24 hours.
Study burden and risks
Hospitalization during study period (5 to 7 days). Daily physical examination
and daily 1 oral dose of pantoprazol. Twice ECG and once buccal cell collection.
For PK and PK/PD patients : 4 bloodsamples on day 1.
All patients : 2 bloodsamples on day 6. (Total amount of blood less than 3 - 4
mL). The patient may have pain, swelling, or bruising where his/her blood is
collected.
PD and PK/PD patients: Twice pH-metry: First during screening and second on
day6. pH-metry last 24 hours. The doctor will place a pH probe through one
nostril down the back of the throat, and into the stomach. Location by
radiography or fluoroscopy. Risks associated with the pH probe are nose
bleeding, sinus discomfort and sore throat. Common (1-10 %) adverse events are
headache and diarrhea.
Spicalaan 31
2132JG Hoofddorp
NL
Spicalaan 31
2132JG Hoofddorp
NL
Listed location countries
Age
Inclusion criteria
1. Male or female hospitalized patients admitted to a neonatal intensive care unit (NICU) or special care nursery, at the time of enrollment. 2. Have a clinical indication for acid suppression to treat a presumptive diagnosis of GERD based on clinical symptoms suggestive of GERD and/or objective tests diagnostic of GERD. NOTE: Disorders associated with or worsened by GERD, objective tests suggestive of GERD, and/or aspiration in conjunction with GERD should also be noted. These are considered supportive documentation of the clinical diagnosis 3. Be either term or post-term infants within the neonatal period ( not older than 28 days), or be preterm infants with a corrected age of less than 44 weeks.4. Have a body weight of at least 1500 grams. 5. Patients must be able to tolerate oral feeding and swallow the test article.
Exclusion criteria
1. Cardiovascular instability, life-threatening arrhythmia, previous cardiopulmonary arrest, or mechanical ventilation.2. Known human immunodeficiency virus (HIV) or clinical manifestations of acquired immune deficiency syndrome (AIDS) or other significant immunodeficiency disorder or malignancy.3. Clinically significant laboratory test abnormality:a. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level 2 times upper limit of normal (ULN).b. Alkaline phosphatase 2 times ULN (age-corrected).4. Known history of positive serologic test for hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibody or RNA.5. Known hypersensitivity to proton pump inhibitors (PPIs), including pantoprazole.6. For PK Patients: History of treatment with PPIs within 24 hours before the first (1st) dose of test article.For PK/PD or PD Patients: History of treatment with PPIs within 7 days before the first (1st) dose of test article.7. For PK Patients: Use of histamine-2-receptor antagonists (H2RAs) within 24 hours before the first (1st) dose of test article. For PK/PD or PD Patients: Use of H2RAs within 3 days before the first (1st) dose of test article.8. Use of antacids within 2 hours before or after test article administration. Use of antacids is also prohibited 2 hours before or during pH-metry.9. Use of warfarin, carbamazepine, or phenytoin as well as rifampin for any disorder from at least 24 hours before the 1st dose of test article until after the final study procedure.10. Significant renal or hepatic disease.11. Any life-threatening condition that would make it unlikely for the patient to be discharged from the hospital.12. Participation in any other investigational study within 30 days before the administration of test article without prior approval of the Wyeth Research, (WR) Medical Monitor.13. PD or PK/PD patients receiving 24-hour continuous enteral feeding or any feeding more frequently than every 3 hours.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2006-001473-24-NL |
| CCMO | NL15488.078.07 |