The assessment of the effectiveness and safety of rabeprazole sodium compared with placebo in the treatment of gastrointestinal esophageal reflux disease (GERD) in infants 1 to 11 months of age

• Register: EUCTR
• Last refreshed on: 22 October 2012
• Main ID: EUCTR2008-004847-12-BG
• Date of registration: 20/01/2010
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International NV
• Public title: The assessment of the effectiveness and safety of rabeprazole sodium compared with placebo in the treatment of gastrointestinal esophageal reflux disease (GERD) in infants 1 to 11 months of age
• Scientific title: A Multicenter, 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/Erosive Gastroesophageal Reflux Disease (GERD)
• Date of first enrolment: 22/03/2010
• Target sample size: 300
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-004847-12
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: Withdrawal study If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Australia, Belgium, Bulgaria, Denmark, Hungary, Israel, Italy, Netherlands, Poland, South Africa, United States

Contacts

• Name: Clinical Registry Group
• Affiliation: Janssen-Cilag International NV

• Name: Clinical Registry Group
• Affiliation: Janssen-Cilag International NV

Key inclusion & exclusion criteria

Inclusion criteria:
Potential subjects must satisfy all of the following criteria to be enrolled in the open-label treatment period of the study:

• Male or female, 1 to 11 months of age, who can be term or post-term infants beyond the neonatal period but less than 12 months of age or preterm infants with a corrected age of at least 44 weeks but less than 12 months;

• Have a diagnosis of suspected GERD, symptomatic GERD, or endoscopically or histologically proven GERD based on the presence of recurrent vomiting or regurgitation with at least 1 of the following characteristics:
– Poor weight gain as defined by failure to thrive;
– Irritability, excessive crying, or disturbed sleep considered abnormal by both the parent(s) and the physician (but not consistent with a diagnosis of colic); and/or
– Refusal to eat even if hungry or arching back at meals;

• Body weight between 3.4 and 14.0 kg, inclusive;

• Have an I-GERQ-R score >16;

• There is 1 individual (parent, legal guardian, or other individual experienced in the care of the subject) who can be designated as the primary caregiver to complete the daily and weekly assessments and ensure compliance with study drug administration and visit attendance. However, if the subject is not under continuous care of the primary caregiver (eg, attends day care, has a nanny), there is a secondary caregiver who can be delegated to carry out any/all of the primary caregiver's responsibilities. It is anticipated that no additional caregivers will be needed for these purposes during the course of the study.

• Parents of subjects (preferably both parents, if available) or their legally-acceptable representatives must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to enroll their infant in the study.

NOTE: Infants who have been receiving thickened feeds as management for GERD symptoms before screening, and whose parent(s) agree to continue administration of the same type of thickened feeds and to record the type and frequency for the duration of the study, are eligible. However, initiation of thickened feeds as management for GERD symptoms during the study is prohibited.
Are the trial subjects under 18? yes
Number of subjects for this age range: 300
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:
Potential subjects who meet any of the following criteria will be excluded from participating in the study:

• History of confirmed acute life-threatening events due to GERD;

• Documented pyloric stenosis;

• Have a confirmed diagnosis of cow's milk allergy or eosinophilic gastroenteropathy by biopsy or allergy testing (symptoms include, but are not limited to, diarrhea, rhinitis, atopic dermatitis);

• Have taken PPIs or H2-blockers within the 3 days before entry into the open-label treatment period;

• Have taken sucralfate or any medication affecting gastrointestinal motility such as caffeine, baclofen, erythromycin, metoclopramide, digoxin or digitalis preparations, ketoconazole, theophylline, domperidone or antacids within 3 days before entry into the open-label treatment period;

• Have clinically relevant laboratory values outside the normal age-appropriate reference range confirmed by a repeat measurement within 7 days. (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 the abnormal values are not clinically relevant. Laboratory results performed within 7 days of screening are
permitted, in lieu of a repeat laboratory draw);

• History of organ system disease or any condition that, in the opinion of the investigator, would compromise subject safety;

• Have a history of allergies/sensitivity to PPIs or any inactive ingredients
in the study drug formulation;

• The subject is breastfed and the mother is taking PPIs (subjects who are
breastfed and the mother is taking H2 receptor antagonists will not be
excluded);

• Received an investigational drug or used an investigational medical device within 30 days before the planned start of treatment, with the exception of subjects who have recently participated in RABGRD1003, a PK/PD and safety study of single and multiple doses of rabeprazole in pediatric subjects with GERD 1 to 11 months old. These subjects will be allowed to enroll in RABGRD3004 after the required 3 day washout period off rabeprazole, provided they meet all other eligibility criteria

• The subject's parent(s) or legally-acceptable representative is an employee of the investigator or the study site, with direct involvement in the proposed study, or other studies under the direction of that investigator or the study site, as well as any family members of the employees or the investigator.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Endoscopically proven gastroesophageal reflux disease (GERD) in a paediatric population of 1 to 11 month old subjects
MedDRA version: 14.0 Level: LLT Classification code 10018203 Term: GERD System Organ Class: 10017947 - Gastrointestinal disorders

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Product Name: rabeprazole sodium
Product Code: R128546
Pharmaceutical Form: Granules for oral suspension
INN or Proposed INN: Rabeprazole Sodium
CAS Number: 117976-89-3
Current Sponsor code: R128546
Other descriptive name: E3810
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-
Pharmaceutical form of the placebo: Granules for oral suspension
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: These endpoints will be evaluated based on the daily event log from baseline to end of study.

Main Objective: To determine the efficacy and overall safety of rabeprazole sodium at doses of 5.0 mg and 10.0 mg relative to placebo in infant subjects with GERD who are 1 to 11 months of age at screening.

The primary efficacy endpoint will be measured by the changes from baseline to the end of the study in the Infant Gastroesophageal Reflux Questionnaire-Revised (I-GERQ-R) total score and the Infant Gastroesophageal Reflux Questionnaire-Daily Diary (I-GERQ-DD) total score between the active treatment and placebo groups.

Primary end point(s): The 2 co-primary endpoints for this study are the changes from baseline to the end of the study in the I-GERQ-R total score and the I-GERQ-DD total score.

Secondary Objective: To demonstrate (1) the superiority of rabeprazole sodium to placebo with regard to the change in the Regurgitation subscale score, (2) the superiority of rabeprazole sodium to placebo with regard to the change in the Discomfort subscale score and (3) the superiority of rabeprazole sodium to placebo with regard to the change in the Eating Behavior subscale score, all (1, 2 & 3) from the I-GERQ-DD from baseline to the end of the study between the active treatment and placebo groups;

To demonstrate the superiority of rabeprazole sodium to placebo with regard to the changes in the frequency and volume of regurgitation

To demonstrate the superiority of rabeprazole sodium to placebo with regard to the change in the weight-for-age Z-score from baseline to the end of the study

To collect sparse PK samples for a population PK analysis to include with data from previous studies in pediatric and adult subjects.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: These endpoints will be evaluated based on the daily event log from baseline to end of study.

Secondary end point(s): Three subscales from the I-GERQ-DD will be used as clinically relevant secondary endpoints. The 3 subscales are the Regurgitation subscale (number of
times and amount of regurgitation during a usual episode), the Discomfort subscale (regurgitation uncomfortable, crying during or after feeding, frequency of crying, frequency of crying after regurgitation, arching back), and the Eating Behavior subscale (refuses a feeding and stops eating soon after starting)

Secondary ID(s)

RABGRD3004

2008-004847-12-HU

Source(s) of Monetary Support

Johnson and Johnson PRD