A Study of Esomeplazole (D961H) in Japanese Paediatric Patients With Reflux Esophagitis, Gastric Ulcer or Duodenal Ulcer

Study Overview
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Brief Summary
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This is an open label, parallel group, multi-centre, phase III study to assess the safety and efficacy of D961H in maintenance therapy following initial healing therapy in Japanese paediatric patients with reflux esophagitis, and to assess the safety and efficacy of D961H in Japanese paediatric patients treated with long term non-steroidal anti-inflammatory drugs or low-dose aspirin therapy who have a documented medical history of gastric ulcer or duodenal ulcer diagnosis. Doses of D961H in this study is set for the 2 groups (weight more than equal 10 kg to less than 20 kg and weight more than equal 20 kg) in the maintenance therapy for healed reflux esophagitis group and the prevention of gastric ulcer or duodenal ulcer recurrence by non-steroidal anti-inflammatory drugs or low-dose aspirin therapy group, Primary endpoints are evaluated at week 32. Further, this study is designed to evaluate the long term efficacy and safety of D961H for a maximum of 52 weeks, in consideration of the medical needs for long term proton pump inhibitor treatment. Patient can continue study treatment up to 52 weeks, if they want

Detailed Description
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Subjects are allocated to four groups based on their disease and weight. Number of Subjects Maintenance therapy for healed reflux esophagitis study part: Group1:aged 1 to 14 years (weight more than equal 10 kg to less than 20 kg ), Maintenance phase, n=5 to 10 Group2:aged 1 to 14 years (weight more than equal 20 kg), Maintenance phase, n=10 to 20 Prevention of gastric ulcer or duodenal ulcer recurrence associated with long term non-steroidal anti-inflammatory drugs or low-dose aspirin therapy study part: Group3:aged 1 to 14 years (weight more than equal 10 kg to less than 20 kg), n=5 to 10 at Week 0 Group4:aged 1 to 14 years (weight more than equal 20 kg), n=10 to 20 at Week 0 All subjects have a D961H administration for 32 or 52 weeks. all esophagogastroduodenoscopy findings are reviewed by central evaluation committee and study is conducted based on the judgement of central evaluation committee. Data are entered in electric data capture system at study site by site staffs and all data are verified with source data by site monitors during the study. Analyses will be performed by AstraZeneca or its representatives. A comprehensive statistical analysis plan will be developed and finalised before database lock and will describe the subject populations to be included in the analyses, and procedures for accounting for missing, unused, and spurious data. This section is a summary of the planned statistical analyses of the primary and secondary endpoints. Any deviations from this plan will be reported in the clinical study report. Efficacy analyses are intended for Efficacy Analysis Set. ・Efficacy Analysis Set:All subjects who take at least 1 dose of the investigational product and have at least 1 efficacy datum assessment during the maintenance/prevention therapy period, and who have no important protocol deviation. All safety analyses are performed on the Safety Analysis Set. ・Safety Analysis Set:All subjects who take at least 1 dose of the investigational product and have any post-treatment assessment. Frequency and incidence rate of adverse events (AEs), serious adverse events (SAEs), discontinuation of investigational product due to adverse events (DAEs) and other significant adverse events (OAEs) will be presented by MedDRA System Organ Class (SOC) and Preferred Term (PT) for each group. In addition, summaries of AEs will be further broken down by maximum intensity and relationship to the investigational product as assigned by investigators

Official Title
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An Open Label, Parallel Group, Multi-centre, Phase III Study to Assess the Efficacy and Safety of D961H for the Maintenance Therapy Following Initial Treatment in Japanese Paediatric Patients With Reflux Esophagitis and for the Prevention of Recurrence of Gastric Ulcer or Duodenal Ulcer in Japanese Paediatric Patients Treated With Non-steroidal Anti-inflammatory Drugs or Low-dose Aspirin

Conditions
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Reflux Esophagitis, Gastric Ulcer, Duodenal Ulcer

Intervention / Treatment
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* Drug: D961H capsule 10mg
* Drug: D961H sachet 10mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For healed reflux esophagitis study Endoscopically verified reflux esophagitis, Grade A or higher according to the Los Angels classification as judged by central evaluation committee. For prevention of gastric ulcer or duodenal ulcer recurrence study Patients with documented medical history of gastric ulser or duodenal ulser diagnosis based on upper gastrointestinal symptoms, fecal occult blood, esophagogastroduodenoscopy findings, etc. Exclusion Criteria: Patients less than 10 kg in weight. Use of any other investigational compounds or participations in another clinical trial within 4 weeks prior to the enrolment. Significant clinical illness within 4 weeks prior to the informed consent Previous total gastrectomy. Presence of hepatic diseases or other conditions that could interfere with evaluation of the study as judged by investigators. etc.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 14 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: An open label, parallel four group, multi-centre, phase III study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group1<br>Initial healing phase (8 weeks), D961H 10 mg once-daily; Maintenance phase (24 or 44 weeks), D961H 10 mg once-daily | Drug: D961H capsule 10mg<br>* All Groups can select either capsule or sachet during the study.<br>* Other names: esomeprazole;Drug: D961H sachet 10mg<br>* All Groups can select either capsule or sachet during the study.<br>* Other names: esomeprazole;|
| Experimental: Group2<br>Initial healing phase (8 weeks), D961H 20 mg once-daily; Maintenance phase (24 or 44 weeks) starts with D961H 10 mg once-daily and may be increased to 20 mg once-daily based on investigator's discretion | Drug: D961H capsule 10mg<br>* All Groups can select either capsule or sachet during the study.<br>* Other names: esomeprazole;Drug: D961H sachet 10mg<br>* All Groups can select either capsule or sachet during the study.<br>* Other names: esomeprazole;|
| Experimental: Group3<br>D961H 10 mg once-daily (32 or 52 weeks) | Drug: D961H capsule 10mg<br>* All Groups can select either capsule or sachet during the study.<br>* Other names: esomeprazole;Drug: D961H sachet 10mg<br>* All Groups can select either capsule or sachet during the study.<br>* Other names: esomeprazole;|
| Experimental: Group4<br>D961H starts with 10 mg once-daily, and may be increased to 20 mg once-daily based on investigator's discretion (32 or 52 weeks) | Drug: D961H capsule 10mg<br>* All Groups can select either capsule or sachet during the study.<br>* Other names: esomeprazole;Drug: D961H sachet 10mg<br>* All Groups can select either capsule or sachet during the study.<br>* Other names: esomeprazole;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence/absence of reflux esophagitis relapse | Maintenance therapy for healed reflux esophagitis study part: Presence/absence of reflux esophagitis relapse from 8 to 32 weeks for all subjects by assessment of the composite endpoint (reflux esophagitis -related symptoms or optional esophagogastroduodenoscopy findings) during the maintenance therapy. | 8 to 32 weeks | 
| Adverse events during reflux esophagitis maintenance therapy | Maintenance therapy for healed reflux esophagitis study part: Safety from 8 to 32 weeks for all subjects. | 8 to 32 weeks | 
| Presence/absence of gastric ulcer or duodenal ulcer recurrence | Prevention of gastric ulcer or duodenal ulcer recurrence associated with long term non-steroidal anti-inflammatory drugs or low-dose aspirin therapy study part: Presence/absence of gastric ulcer or duodenal ulcer recurrence from 0 to 32 weeks for all subjects by assessment of the composite endpoint (gastric ulcer or duodenal ulcer-related symptoms or optional esophagogastroduodenoscopy findings) during the prevention therapy. | 0 to 32 weeks | 
| Adverse events during gastric ulcer or duodenal ulcer recurrence prevention therapy | Prevention of gastric ulcer or duodenal ulcer recurrence associated with long term non-steroidal anti-inflammatory drugs or low-dose aspirin therapy study part: Safety from 0 to 32 weeks for all subjects. | 0 to 32 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence/absence of reflux esophagitis relapse | Presence/absence of reflux esophagitis relapse from 8 to 52 weeks for subjects who continued the study treatment after Week 32 by assessment of the composite endpoint (reflux esophagitis-related symptoms or optional esophagogastroduodenoscopy findings) during the maintenance therapy. | 8 to 52 weeks | 
| Adverse events during reflux esophagitis maintenance therapy | Maintenance therapy for healed reflux esophagitis study part: Safety from 8 to 52 weeks for subjects who continued the study treatment after Week 32. | 8 to 52 weeks | 
| Presence/absence of gastric ulcer or duodenal ulcer recurrence | Presence/absence of gastric ulcer or duodenal ulcer recurrence from 0 to 52 weeks for subjects who continued the study treatment after Week 32 by assessment of the composite endpoint (gastric ulcer or duodenal ulcer-related symptoms or optional esophagogastroduodenoscopy findings) during the prevention therapy. | 0 to 52 weeks | 
| Adverse events during gastric ulcer or duodenal ulcer recurrence prevention therapy | Prevention of gastric ulcer or duodenal ulcer recurrence associated with long term non-steroidal anti-inflammatory drugs or low-dose aspirin therapy study part: Safety from 0 to 52 weeks for subjects who continued the study treatment after Week 32. | 0 to 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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D961H, paediatric, reflux esophagitis, gastric ulcer