E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Endoscopically proven gastroesophageal reflux disease (GERD) in a paediatric population of 1 to 11 month old subjects |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10018203 |
E.1.2 | Term | GERD |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Potential subjects must satisfy all of the following criteria to be enrolled in both the open-label and the double-blind treatment periods 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. |
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E.4 | Principal 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, carafate, 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 48 hours before 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;
• Received an investigational drug or used an investigational medical device within 30 days before the planned start of treatment;
• 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. |
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E.5 End points |
E.5.1 | 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.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 55 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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As specified in the protocol |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 12 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 12 |