A Pharmacokinetics, Pharmacodynamics and Safety Study of Rabeprazole in New Born Infants With Gastroesophageal Reflux Disease (GERD)

This study has been completed.
Sponsor:
Collaborator:
Eisai Inc.
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT00855361
First received: March 2, 2009
Last updated: April 26, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Gastroesophageal Reflux
Drug: Rabeprazole sodium
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pharmacokinetic, Pharmacodynamic and Short-term Safety Study of Single and Multiple Day Doses of Rabeprazole Sodium in Neonates and Pre-term Infants With a Corrected Age of Less Than 44 Weeks With a Presumptive Diagnosis of GERD

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Rabeprazole plasma concentrations (Parts 1 and 2) [ Time Frame: Up to Day 5 ] [ Designated as safety issue: No ]
  • Thioether metabolite plasma concentrations (Parts 1 and 2) [ Time Frame: Up to Day 5 ] [ Designated as safety issue: No ]
  • The change from baseline in intraesophageal H+ concentration (Parts 1 and 2) [ Time Frame: Baseline, Day 5 ] [ Designated as safety issue: No ]
  • The change from baseline in intragastric H+ concentration (Parts 1 and 2) [ Time Frame: Baseline, Day 5 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The number of patients with adverse events as a measure of safety and tolerability [ Time Frame: Approximately 8 weeks ] [ Designated as safety issue: No ]

Enrollment: 69
Study Start Date: July 2009
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   up to 44 Weeks
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must need a feeding tube in place for enteral alimentation (complete or partial) and be in a neonatal intensive care unit or step down unit
  • Patients participating in the pHmetry assessment must be in need of this assessment
  • New born, neonate or pre-term infants less than 44 weeks with a minimum weight of 0.8 kg and with a presumptive diagnosis of GERD
  • Patients who have been treated with, or are currently receiving a proton pump inhibitor (PPI), H2-blockers or antacids
  • Patients should be generally healthy, other than for the presence of GERD.

Exclusion Criteria:

  • A history of or current clinically significant medical illness (excluding GERD, asthma, reactive airway disease or cystic fibrosis-dependant GERD)
  • Continuous drip tube feeding with formula or breast milk
  • Patients whose mothers are taking PPIs and who are pumping breast milk to be fed to their infants
  • Continuous positive airway pressure (CPAP) delivered via nasal prong or oral mask
  • Serum concentrations of hepatic transaminases > 3-fold higher than the upper limit of normal for age creatinine values = 106 micromoles/L
  • Clinically relevant abnormal laboratory values
  • Treatment with full therapeutic doses of sucralfate or any medication that affects gastrointestinal motility such as baclofen, erythromycin, metoclopramide, cisapride, or domperidone
  • A history of allergy or sensitivity to PPIs or to their inactive ingredients
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00855361

Locations
United States, California
Orange, California, United States
United States, District of Columbia
Washington, District of Columbia, United States
United States, Georgia
Augusta, Georgia, United States
United States, Illinois
Maywood, Illinois, United States
United States, Kentucky
Louisville, Kentucky, United States
United States, Louisiana
Shreveport, Louisiana, United States
United States, Michigan
Lansing, Michigan, United States
United States, Nebraska
Omaha, Nebraska, United States
United States, New York
Brooklyn, New York, United States
United States, Ohio
Toledo, Ohio, United States
Germany
Aachen, Germany
Poland
Bydgoszcz, Poland
Lublin Poland, Poland
Odz, Poland
Poznan N/A, Poland
United Kingdom
Barnsley N/A, United Kingdom
Manchester, United Kingdom
Preston, United Kingdom
Sheffield, United Kingdom
Sponsors and Collaborators
Janssen Research & Development, LLC
Eisai Inc.
Investigators
Study Director: Janssen Research & Development, LLC C. Clinical Trial Janssen Research & Development, LLC
  More Information

Additional Information:
No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT00855361     History of Changes
Other Study ID Numbers: CR014824, RABGRD1005
Study First Received: March 2, 2009
Last Updated: April 26, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Janssen Research & Development, LLC:
Gastroesophageal Reflux
Erosive Gastroesophageal Reflux Disease
Ulcerative Gastroesophageal Reflux Disease
Endoscopy
Pediatrics
GERD
Rabeprazole, Rabeprazole sodium
AcipHex

Additional relevant MeSH terms:
Gastroesophageal Reflux
Esophageal Motility Disorders
Deglutition Disorders
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Rabeprazole
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Ulcer Agents
Gastrointestinal Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 24, 2014