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

Phase 3

Completed

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

Interventions: Drug: D961H sachet 10 mg
Drug: D961H capsule 20 mg
Drug: D961H capsule 10mg

Registration Number: NCT02153398

Lead Sponsor: AstraZeneca

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 55

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1: D961H sachet 10 mg	D961H sachet 10 mg	Age: ≥1 year Weight: \<20 kg
Group 5: D961H capsule 20 mg	D961H capsule 20 mg	Age: 12 to 14 years Weight: ≥20 kg
Group 3: D961H capsule 20 mg	D961H capsule 20 mg	Age: ≥1 year to 11years Weight: ≥20 kg
Group 2: D961H capsule 10mg	D961H capsule 10mg	Age: ≥1 year to 11years Weight: ≥20 kg
Group 4: D961H capsule 10 mg	D961H capsule 10mg	Age: 12 to 14 years Weight: ≥20 kg

Primary Outcome Measures

Name	Time	Method
Disappearance of Heartburn at Week 8 by Investigators	8 weeks	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.
Aggravation of Regurgitation at Week 8 by Patient Diaries	8 weeks	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.
Disappearance of Epigastric Pain at Week 8 by Patient Diaries	8 weeks	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.
Disappearance of Regurgitation at Week 8 by Patient Diaries	8 weeks	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.
Aggravation of Regurgitation at Week 8 by Investigators	8 weeks	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.
Disappearance of Heartburn at Week 8 by Patient Diaries	8 weeks	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.
Aggravation of Heartburn at Week 8 by Patient Diaries	8 weeks	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.
Aggravation of Epigastric Pain at Week 8 by Patient Diaries	8 weeks	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.
Aggravation of Upper Abdominal Discomfort at Week 8 by Patient Diaries	8 weeks	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.
Disappearance of Upper Abdominal Discomfort at Week 8 by Patient Diaries	8 weeks	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.
Disappearance of Epigastric Pain at Week 8 by Investigators	8 weeks	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.
Disappearance of Upper Abdominal Discomfort at Week 8 by Investigators	8 weeks	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.
Disappearance of Regurgitation at Week 8 by Investigators	8 weeks	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.
Aggravation of Heartburn at Week 8 by Investigators	8 weeks	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.
Aggravation of Epigastric Pain at Week 8 by Investigators	8 weeks	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.
Aggravation of Upper Abdominal Discomfort at Week 8 by Investigators	8 weeks	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.

Secondary Outcome Measures

Name	Time	Method
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
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
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
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