A Phase I/III Study of D961H 10 mg and 20 mg in Japanese Paediatric Patients With Gastrointestinal Acid Related Diseases

Study Overview
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Brief Summary
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The objective of this study is to assess the safety, pharmacokinetics, pharmacodynamics and efficacy of repeated once daily oral administration of D961H 10 mg and D961H 20 mg in Japanese paediatric patients aged 1 to 14 years old who either have a diagnosis of or are suspected to have gastric ulcer (GU), duodenal ulcer (DU), anastomotic ulcer (AU), non-erosive reflux esophagitis disease (NERD), reflux esophagitis (RE) or Zollinger-Ellison syndrome.

Official Title
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An Open-label, Parallel-group, Multi-centre, Phase I/III Study to Assess the Safety, Pharmacokinetics, Pharmacodynamics and Efficacy of Repeated Once-daily Oral Administration of D961H 10 mg and D961H 20 mg in Japanese Paediatric Patients 1 to 14 Years Old With Gastrointestinal Acid Related Diseases

Conditions
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Gastric Ulcer (GU), Duodenal Ulcer (DU), Anastomotic Ulcer (AU), Non-erosive Reflux Esophagitis Disease (NERD), Reflux Esophagitis (RE), Zollinger-Ellison Syndrome

Intervention / Treatment
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* Drug: D961H sachet 10 mg
* Drug: D961H capsule 10mg
* Drug: D961H capsule 20 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of signed written informed consent from the patient's guardian Patients aged ≥ 1 year to 14 years old Patients who have a diagnosis of or suspected to have GU, DU, AU, NERD, RE or Zollinger-Ellison syndrome. 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 randomisation/registration. Significant clinical illness within 4 weeks prior to the registration Presence of hepatic diseases or other conditions that could interfere with evaluation of the study as judged by the investigators. Positive for pregnancy test by urinary or lactation for post-menarchal females. Previous total gastrectomy

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: D961H sachet 10 mg<br>Age: ≥1 year Weight: <20 kg | Drug: D961H sachet 10 mg<br> <br> |
| Experimental: Group 2: D961H capsule 10mg<br>Age: ≥1 year to 11years Weight: ≥20 kg | Drug: D961H capsule 10mg<br> <br> |
| Experimental: Group 3: D961H capsule 20 mg<br>Age: ≥1 year to 11years Weight: ≥20 kg | Drug: D961H capsule 20 mg<br> <br> |
| Experimental: Group 4: D961H capsule 10 mg<br>Age: 12 to 14 years Weight: ≥20 kg | Drug: D961H capsule 10mg<br> <br> |
| Experimental: Group 5: D961H capsule 20 mg<br>Age: 12 to 14 years Weight: ≥20 kg | Drug: D961H capsule 20 mg<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disappearance of Heartburn at Week 8 by Patient Diaries | The disappearance of heartburn was assessed by the intensity of the symptom at Week 8. Patients who recognized disappearance of heartburn were defined as those who selected Mild, Moderate, or Severe to the question about the intensity in the patient diary at pre-dose and had the maximum intensity of None at Week 8. | 8 weeks | 
| Disappearance of Epigastric Pain at Week 8 by Patient Diaries | The disappearance of epigastric pain was assessed by the intensity of the symptom at Week 8. Patients who recognized disappearance of epigastric pain were defined as those who selected Mild, Moderate, or Severe to the question about the intensity in the patient diary at pre-dose and had the maximum intensity of None at Week 8. | 8 weeks | 
| Disappearance of Upper Abdominal Discomfort at Week 8 by Patient Diaries | The disappearance of upper abdominal discomfort was assessed by the intensity of the symptom at Week 8. Patients who recognized disappearance of upper abdominal discomfort were defined as those who selected Mild, Moderate, or Severe to the question about the intensity in the patient diary at pre-dose and had the maximum intensity of None at Week 8. | 8 weeks | 
| Disappearance of Regurgitation at Week 8 by Patient Diaries | The disappearance of regurgitation was assessed by the intensity of the symptom at Week 8. Patients who recognized disappearance of regurgitation were defined as those who selected Mild, Moderate, or Severe to the question about the intensity in the patient diary at pre-dose and had the maximum intensity of None at Week 8. | 8 weeks | 
| Aggravation of Heartburn at Week 8 by Patient Diaries | The aggravation of heartburn was assessed by the intensity of the symptom at Week 8. Patients who recognized aggravation of heartburn were defined as those who selected None to the question about the intensity in the patient diary at pre-dose and had the maximum intensity of Mild, Moderate or Severe at Week 8. | 8 weeks | 
| Aggravation of Epigastric Pain at Week 8 by Patient Diaries | The aggravation of epigastric pain was assessed by the intensity of the symptom at Week 8. Patients who recognized aggravation of epigastric pain were defined as those who selected None to the question about the intensity in the patient diary at pre-dose and had the maximum intensity of Mild, Moderate or Severe at Week 8. | 8 weeks | 
| Aggravation of Upper Abdominal Discomfort at Week 8 by Patient Diaries | The aggravation of upper abdominal discomfort was assessed by the intensity of the symptom at Week 8. Patients who recognized aggravation of upper abdominal discomfort were defined as those who selected None to the question about the intensity in the patient diary at pre-dose and had the maximum intensity of Mild, Moderate or Severe at Week 8. | 8 weeks | 
| Aggravation of Regurgitation at Week 8 by Patient Diaries | The aggravation of regurgitation was assessed by the intensity of the symptom at Week 8. Patients who recognized aggravation of regurgitation were defined as those who selected None to the question about the intensity in the patient diary at pre-dose and had the maximum intensity of Mild, Moderate or Severe at Week 8. | 8 weeks | 
| Disappearance of Heartburn at Week 8 by Investigators | The investigators assessed the presence/absence and the intensity of heartburn at baseline and Week 8 based on questioning the patients or patients' guardians and the patient diary. Patients who recognized disappearance of heartburn were defined as those who had a heartburn at pre-dose and did not have the corresponding symptoms at Week 8 judged by investigators. | 8 weeks | 
| Disappearance of Epigastric Pain at Week 8 by Investigators | The investigators assessed the presence/absence and the intensity of epigastric pain at baseline and Week 8 based on questioning the patients or patients' guardians and the patient diary. Patients who recognized disappearance of epigastric pain were defined as those who had an epigastric pain at pre-dose and did not have the corresponding symptoms at Week 8 judged by investigators. | 8 weeks | 
| Disappearance of Upper Abdominal Discomfort at Week 8 by Investigators | The investigators assessed the presence/absence and the intensity of upper abdominal discomfort at baseline and Week 8 based on questioning the patients or patients' guardians and the patient diary. Patients who recognized disappearance of upper abdominal discomfort were defined as those who had an upper abdominal discomfort at pre-dose and did not have the corresponding symptoms at Week 8 judged by investigators. | 8 weeks | 
| Disappearance of Regurgitation at Week 8 by Investigators | The investigators assessed the presence/absence and the intensity of regurgitation at baseline and Week 8 based on questioning the patients or patients' guardians and the patient diary. Patients who recognized disappearance of regurgitation were defined as those who had a regurgitation at pre-dose and did not have the corresponding symptoms at Week 8 judged by investigators. | 8 weeks | 
| Aggravation of Heartburn at Week 8 by Investigators | The investigators assessed the presence/absence and the intensity of heartburn at baseline and Week 8 based on questioning the patients or patients' guardians and the patient diary. Patients who recognized aggravation of heartburn were defined as those who had no heartburn at pre-dose and did have any of the corresponding symptoms at Week 8 judged by investigators. | 8 weeks | 
| Aggravation of Epigastric Pain at Week 8 by Investigators | The investigators assessed the presence/absence and the intensity of epigastric pain at baseline and Week 8 based on questioning the patients or patients' guardians and the patient diary. Patients who recognized aggravation of epigastric pain were defined as those who had no epigastric pain at pre-dose and did have any of the corresponding symptoms at Week 8 judged by investigators. | 8 weeks | 
| Aggravation of Upper Abdominal Discomfort at Week 8 by Investigators | The investigators assessed the presence/absence and the intensity of upper abdominal discomfort at baseline and Week 8 based on questioning the patients or patients' guardians and the patient diary. Patients who recognized aggravation of upper abdominal discomfort were defined as those who had no upper abdominal discomfort at pre-dose and did have any of the corresponding symptoms at Week 8 judged by investigators. | 8 weeks | 
| Aggravation of Regurgitation at Week 8 by Investigators | The investigators assessed the presence/absence and the intensity of regurgitation at baseline and Week 8 based on questioning the patients or patients' guardians and the patient diary. Patients who recognized aggravation of regurgitation were defined as those who had no regurgitation at pre-dose and did have any of the corresponding symptoms at Week 8 judged by investigators. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Plasma Concentration-time Curve During a Dosing Interval (AUCtau) of Esomeprazole After at Least 5 Days of Repeated Dose |  | 0, 0.5, 1, 1.5, 2, 3, 4 and 6 hours post-dose after at least 5 days of repeated dose | 
| AUC From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) of Esomeprazole After at Least 5 Days of Repeated Dose |  | 0, 0.5, 1, 1.5, 2, 3, 4 and 6 hours post-dose after at least 5 days of repeated dose | 
| Maximum Plasma Concentration (Cmax) of Esomeprazole After at Least 5 Days of Repeated Dose |  | 0, 0.5, 1, 1.5, 2, 3, 4 and 6 hours post-dose after at least 5 days of repeated dose | 
| Time to Reach Maximum Plasma Concentration (Tmax) of Esomeprazole After at Least 5 Days of Repeated Dose |  | 0, 0.5, 1, 1.5, 2, 3, 4 and 6 hours post-dose after at least 5 days of repeated dose | 
| Elimination Half-life (t1/2) of Esomeprazole After at Least 5 Days of Repeated Dose |  | 0, 0.5, 1, 1.5, 2, 3, 4 and 6 hours post-dose after at least 5 days of repeated dose | 
| Apparent Total Clearance (CL/F) of Esomeprazole After at Least 5 Days of Repeated Dose |  | 0, 0.5, 1, 1.5, 2, 3, 4 and 6 hours post-dose after at least 5 days of repeated dose | 
| Apparent Volume of Distribution (Vz/F) of Esomeprazole After at Least 5 Days of Repeated Dose |  | 0, 0.5, 1, 1.5, 2, 3, 4 and 6 hours post-dose after at least 5 days of repeated dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastric ulcer (GU), Duodenal ulcer (DU), Anastomotic ulcer (AU), Non-erosive reflux esophagitis disease (NERD), Reflux esophagitis (RE), Zollinger-Ellison syndrome