| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Gastroesophageal Reflux Disease |
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| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10017885 |
| E.1.2 | Term | Gastrooesophageal reflux disease |
| E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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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 |
| Primary: to evaluate the safety of once daily treatment with esomeprazole in relieving GERD-associated symptoms in pediatric patients 1 to 11 years of age, inclusive. |
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| E.2.2 | Secondary objectives of the trial |
Secondary: to evaluate the clinical outcome of once daily treatment with esomeprazole in relieving GERD-associated signs and symptoms in pediatric patients 1 to 11 years of age, inclusive.
Exploratory: to describe the burden of pediatric GERD in children ages 1 to 5 years of age, inclusive on the parent/guardian from a psychological, social, and economic perspective.
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
For inclusion in the study, patients (or their parents/guardians when applicable) had to fulfill all of the following criteria;
1. Patients’ parents/guardians must have provided written informed consent prior to the execution of any study-related procedures.
2. Patients who were able to comprehend their involvement in a clinical study, including risks and benefits, (typically ≥6 years of age) must have had assent documented by study personnel prior to any study-related procedures.
3. Patients were males or females between 1 and 11 years of age, inclusive and must have weighed ≥8 kg.
4. Patients must have been diagnosed with endoscopically proven GERD by the investigator during the screening period. Patients with a previous (within 2 weeks prior to Visit 1) diagnosis of EE by endoscopy and who were candidates for PPI therapy were not required to have an additional endoscopy at baseline (Visit 1). The established endoscopic evidence was accepted only if there was adequate documentation (ie, complete endoscopic reports, photo documentation). Patients with extraesophageal and/or atypical symptoms (ie, failure to thrive, reactive airway disease, etc.) who were candidates for endoscopy qualified for inclusion provided they had endoscopic signs of GERD.
5. Patients who, in the judgment of the investigator, would be considered for treatment with a PPI based on symptoms of pathological GER.
6. Postmenarchal females must have had a negative urine pregnancy test at the time of the screening visit.
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| E.4 | Principal exclusion criteria |
Any of the following was regarded as a criterion for exclusion from the study:
1. Patients who had used a PPI within 7 days prior to randomization (Day 0), including over-the-counter (OTC) omeprazole.
2. Patients who had used any prescription or OTC treatment (other than PPIs) for symptoms of GERD, such as H2RAs or prokinetics, within 72 hours prior to randomization (Day 0). Antacids could have been used, except for those containing bismuth (eg, PEPTO BISMOL® [Procter&Gamble, Cincinnati OH, USA] and Kaopectate® [Pfizer Consumer Healthcare, Morris Plains NJ, USA]).
3. Patients who had a history or current need for resectional or reconstructive surgery of the GI tract (eg, esophagus, stomach, duodenum, jejunum, or colon).
4. Female patients who were taking hormonal contraceptives for medical reasons.
5. Patients who needed to remain on any of the following concomitant medications during the course of the study: bismuth-containing products, barbiturates, anticonvulsants, anticoagulants, narcotics, antineoplastic agents, H2RAs, sucralfate, anti-emetics, systemic steroids (oral and intravenous), pro-motility drugs (eg, cisapride, metoclopramide, domperidone) or macrolide antibiotics such as erythromycin. Use of topical erythromycin was permissible. Occasional doses of nonsteroidal anti-inflammatory drugs (NSAIDs) or salicylates (≤3 days) to treat acute conditions were permissible.
6. Patients who had the following diseases/conditions: active gastrointestinal bleed, active peptic ulcer disease, eosinophilic gastroenteritis, allergic gastroenteropathies, inflammatory bowel disease, bleeding disorders, seizure disorders, acute pancreatitis, metabolic diseases or meningitis. Patients who had a past history (prior to study enrollment) of EE, Duodenal Ulcers (DU), Gastric Ulcers (GU) and/or H. pylori infection were eligible for this study if they satisfied other inclusion/exclusion criteria.
7. Patients with H. pylori infection were evaluated on a case-by-case basis. Absolute exclusions were those children with active gastric or duodenal ulceration associated with H. pylori. If there was no documentation of active ulceration or recent GI bleed, the principal investigator (PI) could have, at their discretion, planned for their anti-Helicobacter antibiotic course after this study was completed, provided the patient’s parents/guardian agreed with the course of treatment.
8. The patient’s endoscopic findings had evidence of advanced esophageal lesions due to GERD or other severe upper GI tract pathology (eg, Barrett’s, stricture, neoplasm).
9. Patients who had other major clinical pathology or developmental abnormalities (eg, including but not limited to esophageal atresia, pyloric stenosis), which might have caused gastrointestinal dysmotility as a secondary manifestation.
10. Patients who had acute respiratory distress within 72 hours prior to randomization (Day 0). These patients were eligible for re-evaluation for inclusion once acute symptoms had subsided.
11. Patients who had abnormal screening laboratory values were excluded when the investigator and/or AstraZeneca determined the abnormalities to be unexplained or clinically significant in a way that would put the patient at risk during study participation.
12. Patients who had any condition that might require major surgery during the course of the study.
13. Patients who had a known hypersensitivity, allergy, or intolerance to any component of esomeprazole or omeprazole.
14. Patients who had used any other investigational compound within 28 days prior to the screening visit. Patients who had used investigational devices or products that were not systemically absorbed within 28 days prior to the screening visit were to be discussed with AstraZeneca on a case-by-case basis prior to randomization (Day 0).
15. Patients who had any condition that, in the judgment of the investigator, made performance of any of the study procedures unsafe, or that made it unlikely the patient would complete the study and all study procedures. These conditions may have included behavioral problems such as Attention Deficit Disorder (ADD) or Pervasive Development Disorders.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary objective of this study was to evaluate the safety of once daily esomeprazole for the treatment of endoscopically proven GERD and GERD-associated symptoms in pediatric patients ages 1 to 11 years, inclusive. The safety variables assessed were changes from baseline in adverse events, clinical laboratory evaluations, physical examination (including medical history), vital signs, and other safety variables. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Safety was assessed during the course of the study and up to 2 weeks post the treatment period |
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| E.5.2 | Secondary end point(s) |
Secondary outcome variable
To evaluate the clinical outcome of once daily treatment with esomeprazole in relieving GERD (gastroesophageal reflux disease)-associated symptoms in pediatric patients ages 1 to 11 years, inclusive.
-changes from baseline in Physician’s Global Assessment
-changes from baseline in daily patient symptom assessments as reported by parent/guardian
-changes from baseline in endoscopic healing of EE (erosive esophagitis)
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Symptoms assessment and Physician's Assessement was done during the course of the treatment period.
Endoscopic evaluation was performed on the last treament visit, Day 56. |
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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 | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| 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 | No |
| 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 | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
Will this trial be conducted at a single site globally?
| No |
| E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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| E.8.7 | Trial has a data monitoring committee | No |
| 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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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
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