A Study of the Safety and Effectiveness of Rabeprazole for the Treatment of Gastroesophageal Reflux Disease (GERD) in Pediatric Patients

Study Overview
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Brief Summary
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The purpose of the study is to access the effectiveness and safety of oral rabeprazole in the treatment of acid-related disorders in pediatric patients, focusing specifically on the manifestation of GERD (symptomatic and erosive types).

Detailed Description
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This is a randomized, double-blind study that consists of two parts. In Part 1, the study will consist of 3 phases: a 14-day screening phase, a double-blind treatment phase of 12 weeks comparing two doses of study drug (0.5 mg/kg or 1.0 mg/kg groups based on patient's body weight), and an end-of-study or early withdrawal phase followed by Part 2, which consists a of double-blind treatment continuation for patients who have achieved healing during the short-term double-blind treatment phase. The double-blind maintenance treatment phase lasts for not more than 24 weeks and is concluded by an end-of-study/early withdrawal visit. During Part 1, patients will be screened and the diagnosis of erosive and non-erosive Gastroesophageal Reflux Disease (GERD) will be made based on clinical symptoms and confirmed by endoscopy/histology after a biopsy. Patients enrolled in the study will receive study drug once daily for 12 weeks. Each day, the parent/caregiver will record the presence and severity of pre-specified GERD symptoms. At Weeks 4 and 8, the investigator will evaluate the response to treatment by assessment of the GERD symptoms. At Week 12, the investigator will perform an endoscopy of the esophagus with a biopsy to confirm that histological healing has occurred. If a patient continues, additional study drug will be dispensed (at the same dose taken during the short-term double-blind treatment phase) and the patient will be scheduled to return every 8 weeks until study drug is discontinued at Week 24 (Part 2) of the double-blind maintenance treatment phase. At the final visit of the maintenance treatment phase Week 24 (Part 2), assessments including an endoscopy of the esophagus with a biopsy be performed for each patient. Assessments of effectiveness include endoscopic and histological grading of biopsy samples, GERD symptom and severity score (symptoms and severity rated daily by the parent/caregiver in an electronic diary), overall GERD symptom relief, Clinical Global Impression of Improvement (CGI-I) score, and the Global Treatment Satisfaction Score. Safety assessments will include the monitoring of concomitant therapies and adverse events throughout the study, clinical laboratory testing (including hematology, clinical chemistry, urinalysis), vital signs, and physical examination including height, weight, and Tanner staging. Oral rabeprazole 2.5 capsules or 5 mg capsules, given once daily at a dose of 0.5 mg/kg or 1.0 mg/kg; short-term treatment phase is 12 weeks; long-term maintenance treatment phase is 24 weeks.

Official Title
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A Multi-Center, Double-Blind, Parallel-Group Study to Evaluate Short-term Safety and Efficacy and Long-Term Maintenance of Two Dose Levels of Rabeprazole Sodium Delayed-Release Pediatric Bead Formulation in 1- to 11-Year Old Pediatric Subjects With Endoscopically Proven GERD

Conditions
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Gastroesophageal Reflux Disease (GERD)

Intervention / Treatment
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* Drug: rabeprazole
* Drug: rabeprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of at least 1 Gastroesophageal Reflux Disease (GERD) symptom within 3 months of screening Positive esophagogastroduodenoscopy Signed informed consent Female patients (if menstruating) must be practicing birth control Exclusion Criteria: Patients with history of esophagitis Patients who have milk protein allergy Patients who have taken Proton Pump Inhibitors or H2-blockers within 3 days Patients who have taken sucralate or any medication that affects gastrointestinal motility Patients with H. pylori Patients with lab values outside the normal age appropriate range Patients who have participated in another trial within 30 days before screening Patients with allergies to Proton Pump Inhibitors

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 11 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rabeprazole 0.5 mg/kg<br>rabeprazole 0.5mg/kg once daily for 12 weeks plus option for F/u another 24 weeks | Drug: rabeprazole<br>* 0.5mg/kg once daily for 12 weeks plus option for F/u another 24 weeks<br>|
| Experimental: Rabeprazole 1.0 mg/kg<br>rabeprazole 1.0 mg/kg once daily for 12 weeks plus option for F/u another 24 weeks | Drug: rabeprazole<br>* 1.0 mg/kg once daily for 12 weeks plus option for F/u another 24 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Patients With Healing by Week 12 (Short-term Double-blind Treatment Phase) | Healing is defined as macroscopically normal esophageal mucosa or histologic normal esophageal mucosa. | 12 weeks | 
| The Percentage of Patients With Healing by Week 36 (Double-blind Maintenance Treatment Phase) | Healing is defined as macroscopically normal esophageal mucosa or histologic normal esophageal mucosa. | 36 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Change From Baseline in the Hetzel and Dent Endoscopic Classification Grade Score (Short-term Double-blind Treatment Phase) | The Hetzel and Dent Classification grades range from 0 (normal esophageal mucosa, no abnormalities noted) to 4 (deep ulcers anywhere in the esophagus or ulceration of more than half of the esophageal mucosa). Higher observed scores indicate more serious condition. For change of baseline, a score of 0 indicates no change; a positive score indicates the condition is worsening, while a negative score indicates an improvement. | Baseline, Week 12 | 
| The Change From Baseline in the Total GERD Symptom and Severity Score (Short-term Double-blind Treatment Phase) | The gastroesophageal reflux disease (GERD) symptom and severity scale measures the frequency (0= Never; 1= 1-2 times; 2= 3-4 times; 3= 5-6 times; 4= 7 or more times) and the severity (1= Mild; 2= Moderate; 3=Severe) of GERD symptoms. The score is defined as the sum of the frequency (0-4) and severity (1-3) of that symptom. The total score is the sum of the scores of all the symptoms and ranges from 12 to 84. Higher scores indicate more serious condition. For change from baseline, 0 indicates no change; a positive score indicates worsening, while a negative score indicates improvement. | Baseline, Week 12 | 
| The Change From Baseline in the Hetzel and Dent Endoscopic Classification Grade Score (Double-blind Maintenance Treatment Phase) | The Hetzel and Dent Classification grades range from 0 (normal esophageal mucosa, no abnormalities noted) to 4 (deep ulcers anywhere in the esophagus or ulceration of more than half of the esophageal mucosa). Higher observed scores indicate more serious condition. For change of baseline, a score of 0 indicates no change; a positive score indicates the condition is worsening, while a negative score indicates an improvement. | Baseline, Week 36 | 
| The Change From Baseline in the Total GERD Symptom and Severity Score (Double-blind Maintenance Treatment Phase) | The gastroesophageal reflux disease (GERD) symptom and severity scale measures the frequency (0= Never; 1= 1-2 times; 2= 3-4 times; 3= 5-6 times; 4= 7 or more times) and the severity (1= Mild; 2= Moderate; 3=Severe) of GERD symptoms. The score is defined as the sum of the frequency (0-4) and severity (1-3) of that symptom. The total score is the sum of the scores of all the symptoms and ranges from 12 to 84. Higher scores indicate more serious condition. For change from baseline, 0 indicates no change; a positive score indicates worsening, while a negative score indicates improvement. | Baseline, Week 36 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rabeprazole, Gastroesophageal Reflux Disease (GERD), Erosive Gastroesophageal Reflux Disease, Ulcerative Gastroesophageal Reflux Disease, Endoscopy, Pediatrics