Gastroesophageal reflux disease (GERD) in neonates and pre-term infants, with a corrected age of less than 44 weeks at the time of the first dose. MedDRA version: 13.1 Level: LLT Classification code 10018203 Term: GERD System Organ Class: 10017947 - Gastrointestinal disorders
Conditions
Interventions
Product Name: rabeprazole sodium
Product Code: R128546
Pharmaceutical Form: Granules
INN or Proposed INN: Rabeprazole Sodium
CAS Number:
Sponsors
Janssen-Cilag International NV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Potential subjects must meet all of the following criteria to participate in the study: • Subjects must be an inpatient in a neonatal intensive care unit (NICU) or step down unit and must need a feeding tube (6 French nasogastric or orogastric) in place for enteral alimentation (complete or partial). Partial oral feedings are allowed. • Subjects participating in the pHmetry assessment must be in need of this assessment for their clinical management in the opinion of the Investigator. • Male and female neonates or pre-term infants, with a corrected age of less than 44 weeks at the time of the first dose, with a minimum weight of 0.8 kg at screening and with a presumptive diagnosis of GERD based on at least one of the following symptoms: recurrent regurgitation, a failure to thrive, coughing, grimacing and discomfort with feeding, an arching position related to feeding, presumed GERD-associated apneic events (apnea or bradycardia episodes associated with oxygen desaturation deemed related to feeding), feeding intolerance manifested by recurrent emesis, regurgitation and irritability, presumed or documented lung aspiration, irritability and apparent discomfort associated with feedings, recurrent pneumonia, recurrent bronchopulmonary disease exacerbated by GERD and observed milk in the mouth or oropharynx. • Subjects who have been treated with, or are currently receiving a PPI, H2-blockers or antacids are eligible, provided they can discontinue the PPIs and H2-blockers for 3 days before dosing and remain off these medications for the duration of the treatment phase. Cimetidine must be discontinued for at least 7 days prior to dosing. The use of antacids will be allowed until 24 hours before dosing and can be used as a substitute for PPIs and H2 blockers until 24 hours before dosing. • Subjects should be generally stable, other than for the presence of GERD. Are the trial subjects under 18? yes Number of subjects for this age range: 72 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range 0 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: Subjects meeting any of the following criteria will be excluded from participating in the study: • A history of or current clinically significant medical illness (excluding GERD, asthma, reactive airway disease or cystic fibrosis-dependant GERD) in the opinion of the investigator that should exclude the subject or which could interfere with the interpretation of the study results. • Continuous drip tube feeding with formula or breast milk (bolus feedings separated by at least 3 hours will be allowed). • Subjects 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. CPAP delivered via an endotracheal tube will be allowed. • Serum concentrations of hepatic transaminases > 3-fold higher than the upper limit of normal for age. Creatinine values = 106 µmol/L (=1.2 mg/dL). • Clinically relevant laboratory values outside of the normal age appropriate range for the infant based on local laboratory values accepted by the investigator. If the results of the testing are not within the laboratory’s reference range for the subject’s age, the subject may be included only if the investigator decides that the abnormal values are not clinically significant. Laboratory results obtained as part of the subject’s routine clinical care in the NICU, if performed within 72 hours prior to screening are allowed, in lieu of an additional blood draw for study laboratory determinations. However, if the normal practice in the neonatal intensive care unit does not include all the protocol-specified laboratory tests, the per-protocol tests must be performed during the screening and end of study phases even if that requires an additional blood draw. • Participation in any clinical study with a study drug or medical device within 30 days or a period less than 10 times the half-life of the respective study drug (if known), whichever is longer, before the first dose of this study drug is scheduled. Exceptions to this include experimental surfactant therapy, short term single dose studies requiring less than 0.2 mL blood draw volume with experimental treatment more than 3 days from the start of this study’s treatment, or any other needed intervention that, in the opinion of the investigator, will not affect the results of the current study. • Treatment with full therapeutic doses of sucralfate or any medication that affects gastrointestinal motility such as baclofen, erythromycin, metoclopramide, cisapride, or domperidone. In addition, digoxin or digitalis preparations and ketoconazole will be excluded within 3 days prior to dosing (or a shorter washout period if agreed to by the investigator and the sponsor). Antacids are allowed to be continued up to 24 hours prior to dosing. Treatment with a PPI or H2-blocker is not allowed within 72 hours prior to dosing; cimetidine should be discontinued for at least 7 days prior to dosing. If PPIs or H2-blockers are discontinued 72 hours prior to dosing, antacids may be substituted for the first 48 hours of that 72 hour washout period, but then must be discontinued for at least 24 hours prior to dosing. • If a subject has been treated with any drug that may be considered a CYP3A4 inhibitor or inducer within 7 days
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: no secondary obiectives;Timepoint(s) of evaluation of this end point: A subject will be considered to have completed the study if the subject has completed all required assessments and received at least 5 doses of the study drug; Main Objective: The objective of this study is to evaluate the pharmacokinetics (PK) using population PK methods, pharmacodynamics (PD) (intraesophageal and intragastric pH, assessment of the overall treatment effect [OTE] [overall GERD symptom relief]) and the short-term safety of rabeprazole after single and multiple dose administration for up to 28 days at one low dose level (Part 1) and two presumed effective dose levels (Part 2) in neonates and pre-term infants, with a corrected age of less than 44 weeks at the time of the first dose, who have been diagnosed with GERD. As this study is an exploratory assessment of the population PK, PD and short-term safety of rabeprazole in neonates and pre-term infants, no formal hypothesis testing is applied. ; Primary end point(s): Subjects will undergo a series of assessments during the course of the study to evaluate the pharmacokinetics, pharmacodynamics and the short-term safety of rabeprazole. A subject will be considered to have completed the study if the subject has completed all required assessments and received at least 5 doses of the study drug. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): N/A;Timepoint(s) of evaluation of this end point: N/A | — |
Countries
Germany, Poland, United Kingdom, United States
Contacts
Public ContactClinical Registry Group
Janssen-Cilag International NV
Outcome results
None listed