Clinical trial NCT00992589: Safety and Efficacy of Rabeprazole in Infants With Gastroesophageal Erosive Reflux Disease (GERD)
Official title: A Multi-Center, Double-Blind, Randomized, Placebo-Controlled, Parallel Group, Withdrawal Study to Evaluate the Safety and Efficacy of Delayed Release Rabeprazole in 1- to 11-Month-Old Pediatric Subjects With Symptomatic/Gastroesophageal Erosive Reflux Disease (GERD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Gastroesophageal Reflux
Keywords: Gastroesophageal Reflux
Gastroesophageal Reflux Disease
GERD
Proton Pump Inhibitor
PPI
Regurgitation
Infants
AcipHex, PARIET
ALFENCE
Lead sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Sponsor class: INDUSTRY
Collaborators: name: Eisai Inc.
First posted: 2009-10-09
Enrollment: 344
Sex: ALL
Minimum age (years): 1
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the effectiveness and safety of rabeprazole sodium, an inhibitor of gastric acid secretion of the protein pump inhibitor (PPI) class, compared with placebo in the treatment of gastrointestinal esophageal reflux disease (GERD) in infants 1 to 11 months of age.

Detailed description: Rabeprazole sodium belongs to the class of drugs known as proton pump inhibitors, which suppress gastric acid secretion. The drug is approved in the United States for the treatment of adults with GERD and other acid-related gastrointestinal disorders, and has been studied in adolescents (older than 12 years of age) with results similar to those in adults. However, the drug has not been studied in children under the age of 12 years. This study focuses on the efficacy and safety of rabeprazole sodium in infants aged 1 to 11 months, the pediatric group in which the prevalence of GERD-related symptoms is the greatest. This is a multicenter, double-blind, randomized, placebo-controlled, parallel-group withdrawal study to compare the efficacy and safety of 2 doses (0.5 mg/kg or 1.0 mg/kg daily) of rabeprazole with placebo in the treatment of infants aged 1 to 11 months who have a diagnosis of suspected GERD, symptomatic GERD, or endoscopically or histologically proven GERD. The study consists of 3 study periods: a screening period of up to 10 days, an open-label treatment period of up to 3 weeks, and a 5-week double-blind treatment period. Patients who have been receiving GERD therapy before screening will have their GERD therapy discontinued for 3 days before entering the open-label treatment period. Patients who have a positive clinical response according to the Clinical Global Impressions - Improvement (CGI-I) scale at the end of the first or second week of the open-label treatment period will enter the double-blind treatment period; those who do not will be withdrawn from the study. A parent, legal guardian, or other individual experienced in the care of the infant will be the primary caregiver, who is responsible for the daily and weekly assessments and study drug administration. Efficacy assessments consist of the Infant Gastroesophageal Reflux Questionnaire Revised (I GERQ-R) total score, the Infant Gastroesophageal Reflux Questionnaire-Daily Diary (I GERQ-DD) total score, the CGI-I, the Global Treatment Satisfaction Score, and the weight-for-age Z-score. Safety assessments include monitoring of concomitant therapies and adverse events throughout the study; clinical laboratory testing (hematology, clinical chemistry, urinalysis), measurement of vital signs (pulse and respiratory rate, blood pressure, temperature); and physical examination including length and weight. The study hypothesis is that rabeprazole sodium is superior to placebo in the treatment of GERD in infants aged 1 to 11 months. Rabeprazole sodium capsule(s) by mouth once a day, 10.0 milligram (mg)/kilogram (kg) for up to 3 weeks during the open-label treatment period and either 5.0 mg/kg or 10.0 mg/kg during the 5-week double-blind treatment period. To give the study drug to the infants, the contents of the capsule(s) are sprinkled onto a small amount of soft food or, as needed, the contents of the capsule(s) may be given in a small amount (5 milliliter \[mL\]) of infant formula or expressed breast milk.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of suspected GERD, symptomatic GERD, or endoscopically or histologically proven GERD, based on frequent vomiting or regurgitation, with at least 1 of the following: a) poor weight gain, or b) irritability, excessive crying or disturbed sleep that both the parent(s) and the doctor consider abnormal (but not due to colic)
* or c) refusal to eat even if hungry or arching of the back during meals
* weight 2.5 kg to 15.0 kg
* I-GERQ-R score \>16
* Have only 1 caregiver in addition to the parent(s)

Exclusion Criteria:

* History of confirmed acute life-threatening events due to GERD
* Known narrowing of the opening from the stomach to the small intestines
* Confirmed diagnosis of cow's milk allergy
* Have taken PPIs or H2-blockers (a class of drugs that inhibit stomach acid production) or any of several drugs that affect the normal movement of the digestive tract (caffeine, theophylline, antacids, erythromycin, and others) within 3 days before entering the study
* Have blood or urine test results that are well above or below the normal range for the infant

Primary outcomes:
measure: Change From Baseline in Average Daily Frequency of Regurgitation (Double-blind Phase/ Baseline Observation Carried Forward)
timeFrame: Baseline, Week 8
measure: Change From Baseline in Weight-for-Age Z-Score (Double-blind Phase/ Baseline Observation Carried Forward)
timeFrame: Baseline, Week 8
measure: Change From Baseline in I-GERQ-R Total Score (Double-blind Phase/ Baseline Observation Carried Forward)
timeFrame: Baseline, Week 8
measure: Change From Baseline in in Weekly Average I-GERQ-DD Total Score (Double-blind Phase/ Baseline Observation Carried Forward)
timeFrame: Baseline, Week 8
Secondary outcomes:
measure: The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period
timeFrame: Baseline, Week 8
measure: Change From Baseline in Weekly Average I-GERQ-DD Regurgitation Subscale Score (Double-blind Phase/ Last Observation Carried Forward)
timeFrame: Baseline, Week 8
measure: Change From Baseline in Weekly Average I-GERQ-DD Discomfort Subscale Score (Double-blind Phase/ Last Observation Carried Forward)
timeFrame: Baseline, Week 8
measure: Change From Baseline in Weekly Average I-GERQ-DD Eating Behavior Subscale Score (Double-blind Phase/ Last Observation Carried Forward)
timeFrame: Baseline, Week 8
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Columbiana
country: United States
state: Alabama
city: Dothan
country: United States
state: Alabama
city: Huntsville
country: United States
state: Alabama
city: Mobile
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state: Alabama
city: Phoenix
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state: Arizona
city: Bentonville
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state: Arkansas
city: Orange
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state: California
city: Centennial
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state: Colorado
city: Thornton
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state: Colorado
city: Maitland
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state: Florida
city: Miami
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state: Florida
city: Augusta
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state: Georgia
city: Park Ridge
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state: Illinois
city: Indianapolis
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state: Indiana
city: Louisville
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state: Kentucky
city: Owensboro
country: United States
state: Kentucky
city: New Orleans
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state: Louisiana
city: Shreveport
country: United States
state: Louisiana
city: Boston
country: United States
state: Massachusetts
city: Worcester
country: United States
state: Massachusetts
city: Flint
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state: Michigan
city: St. Paul
country: United States
state: Minnesota
city: Jackson
country: United States
state: Mississippi
city: Bridgeton
country: United States
state: Missouri
city: Mays Landing
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state: New Jersey
city: Valhalla
country: United States
state: New Jersey
city: Bronx
country: United States
state: New York
city: Buffalo
country: United States
state: New York
city: Utica
country: United States
state: New York
city: Charlotte
country: United States
state: North Carolina
city: Toledo
country: United States
state: Ohio
city: Youngstown
country: United States
state: Ohio
city: Gresham
country: United States
state: Oregon
city: Hershey
country: United States
state: Pennsylvania
city: Chattanooga
country: United States
state: Tennessee
city: Kingsport
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: Laredo
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Tomball
country: United States
state: Texas
city: Fairfax
country: United States
state: Virginia
city: Huntington
country: United States
state: West Virginia
city: Garran
country: Australia
city: Herston
country: Australia
city: Kogarah
country: Australia
city: Parkville
country: Australia
city: Sydney
country: Australia
city: Antwerpen
country: Belgium
city: Brussel
country: Belgium
city: Leuven
country: Belgium
city: Pleven
country: Bulgaria
city: Odense
country: Denmark
city: Budapest
country: Hungary
city: Békéscsaba
country: Hungary
city: Gyulai Ut 18
country: Hungary
city: Gyõr
country: Hungary
city: Miskolc
country: Hungary
city: Nyiregyhaza
country: Hungary
city: Pecs
country: Hungary
city: Szombathely
country: Hungary
city: Veszprem
country: Hungary
city: Veszprém
country: Hungary
city: Haifa
country: Israel
city: Jerusalem
country: Israel
city: Petach Tikvah
country: Israel
city: Petach Tikva
country: Israel
city: Ramat Gan
country: Israel
city: Tiberias
country: Israel
city: Amsterdam
country: Netherlands
city: Nijmegen
country: Netherlands
city: Zwolle
country: Netherlands
city: Bialystok
country: Poland
city: Bydgoszcz N/A
country: Poland
city: Bydgoszcz
country: Poland
city: Czestochowa
country: Poland
city: Rzeszow N/A
country: Poland
city: Rzeszow
country: Poland
city: Torun
country: Poland
city: Warszawa
country: Poland
city: Durbanville
country: South Africa
city: Durban
country: South Africa
city: Panorama
country: South Africa
city: Wynberg
country: South Africa
Study officials:
affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
name: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Sharp WG, Stubbs KH, Adams H, Wells BM, Lesack RS, Criado KK, Simon EL, McCracken CE, West LL, Scahill LD. Intensive, Manual-based Intervention for Pediatric Feeding Disorders: Results From a Randomized Pilot Trial. J Pediatr Gastroenterol Nutr. 2016 Apr;62(4):658-63. doi: 10.1097/MPG.0000000000001043.
citation: Hussain S, Kierkus J, Hu P, Hoffman D, Lekich R, Sloan S, Treem W. Safety and efficacy of delayed release rabeprazole in 1- to 11-month-old infants with symptomatic GERD. J Pediatr Gastroenterol Nutr. 2014 Feb;58(2):226-36. doi: 10.1097/MPG.0000000000000195.
citation: Treem W, Hu P, Sloan S. Normal and proton pump inhibitor-mediated gastrin levels in infants 1 to 11 months old. J Pediatr Gastroenterol Nutr. 2013 Oct;57(4):520-6. doi: 10.1097/MPG.0b013e31829b6914.