The purpose of this study is to evaluate the pharmacokinetics, pharmacodynamics, and the safety of rabeprazole sodium for the treatment of gastroesophageal reflux disease (GERD) in newborns and pre-term infants.
Primary Outcome Measures:
- Rabeprazole plasma concentrations (Parts 1 and 2) [ Time Frame: Up to Day 5 ]
- Thioether metabolite plasma concentrations (Parts 1 and 2) [ Time Frame: Up to Day 5 ]
- The change from baseline in intraesophageal H+ concentration (Parts 1 and 2) [ Time Frame: Baseline, Day 5 ]
- The change from baseline in intragastric H+ concentration (Parts 1 and 2) [ Time Frame: Baseline, Day 5 ]
Secondary Outcome Measures:
- The number of patients with adverse events as a measure of safety and tolerability [ Time Frame: Approximately 8 weeks ]
| Study Start Date:
| Study Completion Date:
| Primary Completion Date:
||December 2011 (Final data collection date for primary outcome measure)
Experimental: Rabeprazole sodium
Drug: Rabeprazole sodium
One single daily dose of rabeprazole sodium 1 mg as a microgranule formulation for up to 28 consecutive days (Part 1), and one single daily dose of rabeprazole sodium 2 or 3 mg as a microgranule formulation for up to 28 consecutive days (Part 2). The study drug will be administered through a nasogastric or orogastric tube.
This is a multi-center Phase I study in newborns and pre-term infants (less than 44 weeks at the time of the first dose). The drug being studied is rabeprazole sodium, the active pharmaceutical ingredient in AcipHex. This study will consist of two parts, Part 1 and Part 2. Each part will consist of three phases, a pre-treatment phase (screening of up to 7 days before the start of treatment), a treatment phase (up to 28 days) and a post treatment phase (at least 14 days, but no more than 21 days after the last dose of study drug). The maximum study length for each patient will therefore be up to 8 weeks. Patients will be monitored patients with a presumptive diagnosis of GERD and who need a feeding tube for enteral alimentation (complete or partial) in place and have been admitted to a newborn intensive care unit or step down unit. The population pharmacokinetics (PK) results together with the pharmacodynamics (ie, pHmetry) data, the safety and tolerability data from Part 1 will be assessed to determine the two dose levels to be studied in Part 2 before the start of dosing. Pharmacokinetics explores how the drug is absorbed in the body, distributed within the body, and how it is removed from the body over time. Pharmacodynamics (PD) studies the action or effects a drug has on the body. All patients in Part 1 will require pH monitoring for clinical management and undergo a 24-hour PD assessment (intraesophageal and intragastric pHmetry). At least 12 patients in Part 2 (at least 6 patients from each dose group) will require pH monitoring and undergo the same PD assessment as patients in Part 1. Patients participating in the pHmetry assessment must be in need of this assessment for their clinical management in the opinion of the Principal Investigator. The intraesophageal and intragastric 24-hour pH PD assessment in both Part 1 and Part 2 will be performed at baseline (Day -1) and after the first dose (Day 1) and fifth dose (Day 5). Sampling for single dose blood level PK evaluations will be performed post-dose on Day 1. Sampling blood level evaluations at the presumed steady-state during multiple dosing will be performed on Day 5. Patients' safety will be monitored throughout the study. At the end of the study, or if any patient prematurely discontinues his/her participation in the study, a safety evaluation will be performed at least 14 days, but no more than 21 days, after the final rabeprazole sodium dose. During the course of the study, after consent each patient will have medical history, a physical, length, weight, vital signs, blood chemistry, and urinalysis. Safety from baseline to the End of Study visit (post-treatment phase) will be evaluated by examining incidence, severity and relationship to the study drug and type of Adverse Events (AEs), urinalysis, physical examination and vital signs. Patients will receive rabeprazole sodium as a single daily dose for up to 28 consecutive days. Patients participating in Part 1 will receive 1.0 mg rabeprazole sodium administered by a nasogastric tube. After four patients complete Part 1, their rabeprazole plasma levels will be assessed and the dose may be increased to 2.0 mg rabeprazole sodium. The population PK results, together with the PD (ie, pHmetry) data, safety and tolerability data from Part 1 will be assessed to determine 2 doses in Part 2.