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

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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00787891

Enrollment

127

Registered

2008-11-10

Start date

2009-01-31

Completion date

2011-01-31

Last updated

2013-01-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Gastroesophageal Reflux Disease (GERD)

Keywords

Gastroesophageal Reflux Disease (GERD), Erosive Gastroesophageal Reflux Disease, Ulcerative Gastroesophageal Reflux Disease, Endoscopy, Pediatrics, Rabeprazole

Brief summary

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

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.

Interventions

DRUGrabeprazole

0.5mg/kg once daily for 12 weeks plus option for F/u another 24 weeks

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

1 Years to 11 Years

Healthy volunteers

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

Design outcomes

Primary

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

Secondary

Measure	Time frame	Description
The Change From Baseline in the Hetzel and Dent Endoscopic Classification Grade Score (Short-term Double-blind Treatment Phase)	Baseline, Week 12	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.
The Change From Baseline in the Total GERD Symptom and Severity Score (Short-term Double-blind Treatment Phase)	Baseline, Week 12	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.
The Change From Baseline in the Hetzel and Dent Endoscopic Classification Grade Score (Double-blind Maintenance Treatment Phase)	Baseline, Week 36	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.
The Change From Baseline in the Total GERD Symptom and Severity Score (Double-blind Maintenance Treatment Phase)	Baseline, Week 36	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.

Participant flow

Pre-assignment details

In this study, 108 patients completed the 12-week phase (Part 1) and were counted for the primary outcome measure (OM). Patients with healing at Week 12 had the option to continue the treatment for 24 weeks. Among the 87 with healing, 64 enrolled into Part 2. Only 52 had the primary efficacy endpoint available and were included in the primary OM.

Participants by arm

Arm	Count
Rabeprazole 0.5 mg/kg Pediatric micro-bead formulation of rabeprazole sodium orally administered.	65
Rabeprazole 1.0 mg/kg Pediatric micro-bead formulation of rabeprazole sodium orally administered.	62
Total	127

Withdrawals & dropouts

Period	Reason	FG000	FG001
Maintenance Double-blind Phase (Part 2)	Adverse Event	0	1
Maintenance Double-blind Phase (Part 2)	Non-Compliance With Study Drug	1	1
Maintenance Double-blind Phase (Part 2)	Other	5	2
Maintenance Double-blind Phase (Part 2)	Withdrawal by Subject	1	3
Short-term Double-blind Phase (Part 1)	Adverse Event	1	2
Short-term Double-blind Phase (Part 1)	Lost to Follow-up	2	2
Short-term Double-blind Phase (Part 1)	Other	0	2
Short-term Double-blind Phase (Part 1)	Physician Decision	1	0
Short-term Double-blind Phase (Part 1)	Protocol Violation	0	1
Short-term Double-blind Phase (Part 1)	Withdrawal by Subject	6	2

Baseline characteristics

Characteristic	Total	Rabeprazole 0.5 mg/kg	Rabeprazole 1.0 mg/kg
Age, Categorical <=18 years	127 Participants	65 Participants	62 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	0 Participants	0 Participants	0 Participants
Age Continuous	5.7 years STANDARD_DEVIATION 3.37	5.9 years STANDARD_DEVIATION 3.49	5.4 years STANDARD_DEVIATION 3.26
Baseline BMI	17.2 kg/cm2 STANDARD_DEVIATION 3.64	17.5 kg/cm2 STANDARD_DEVIATION 4.08	16.8 kg/cm2 STANDARD_DEVIATION 3.11
Sex: Female, Male Female	56 Participants	31 Participants	25 Participants
Sex: Female, Male Male	71 Participants	34 Participants	37 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —
other Total, other adverse events	47 / 65	47 / 62	18 / 33	21 / 31
serious Total, serious adverse events	5 / 65	1 / 62	2 / 33	3 / 31

Outcome results

Primary

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.

Time frame: 12 weeks