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

• D961H sachet 10 mg (Drug)
• D961H capsule 10mg (Drug)
• D961H capsule 20 mg (Drug)

Primary outcomes

• 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.
• 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 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 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 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.
• 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 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.
• 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.
• 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.

Secondary outcomes

• 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]

Sex: All, ages: 1 Year to 14 Years

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

Participant flow

Outcome results

• Disappearance of Heartburn at Week 8 by Patient Diaries (Primary), Number, Participants: Group 1 2; Group 2 0; Group 3 0; Group 4 1; Group 5 3
• Disappearance of Epigastric Pain at Week 8 by Patient Diaries (Primary), Number, Participants: Group 1 2; Group 2 3; Group 3 5; Group 4 1; Group 5 3
• Disappearance of Upper Abdominal Discomfort at Week 8 by Patient Diaries (Primary), Number, Participants: Group 1 3; Group 2 2; Group 3 4; Group 4 2; Group 5 2
• Disappearance of Regurgitation at Week 8 by Patient Diaries (Primary), Number, Participants: Group 1 3; Group 2 2; Group 3 3; Group 4 2; Group 5 4
• Aggravation of Heartburn at Week 8 by Patient Diaries (Primary), Number, participants: Group 1 0; Group 2 0; Group 3 0; Group 4 0; Group 5 0
• Aggravation of Epigastric Pain at Week 8 by Patient Diaries (Primary), Number, participants: Group 1 0; Group 2 0; Group 3 1; Group 4 1; Group 5 1
• Aggravation of Upper Abdominal Discomfort at Week 8 by Patient Diaries (Primary), Number, participants: Group 1 0; Group 2 0; Group 3 2; Group 4 1; Group 5 0
• Aggravation of Regurgitation at Week 8 by Patient Diaries (Primary), Number, participants: Group 1 2; Group 2 0; Group 3 1; Group 4 0; Group 5 0
• Disappearance of Heartburn at Week 8 by Investigators (Primary), Number, Participants: Group 1 2; Group 2 1; Group 3 ; Group 4 2; Group 5 2
• Disappearance of Epigastric Pain at Week 8 by Investigators (Primary), Number, Participants: Group 1 2; Group 2 5; Group 3 4; Group 4 2; Group 5 6
• Disappearance of Upper Abdominal Discomfort at Week 8 by Investigators (Primary), Number, Participants: Group 1 3; Group 2 5; Group 3 4; Group 4 4; Group 5 3
• Disappearance of Regurgitation at Week 8 by Investigators (Primary), Number, Participants: Group 1 3; Group 2 0; Group 3 3; Group 4 1; Group 5 3
• Aggravation of Heartburn at Week 8 by Investigators (Primary), Number, Participants: Group 1 0; Group 2 0; Group 3 0; Group 4 1; Group 5 0
• Aggravation of Epigastric Pain at Week 8 by Investigators (Primary), Number, Participants: Group 1 0; Group 2 0; Group 3 0; Group 4 0; Group 5 0
• Aggravation of Upper Abdominal Discomfort at Week 8 by Investigators (Primary), Number, Participants: Group 1 0; Group 2 0; Group 3 0; Group 4 1; Group 5 0
• Aggravation of Regurgitation at Week 8 by Investigators (Primary), Number, Participants: Group 1 0; Group 2 0; Group 3 1; Group 4 0; Group 5 1
• Area Under the Plasma Concentration-time Curve During a Dosing Interval (AUCtau) of Esomeprazole After at Least 5 Days of Repeated Dose (Secondary), Mean, μmol*h/L: Group 1 7.04 +/- 3.05; Group 2 3.52 +/- 2.35; Group 3 11.05 +/- 5.11; Group 4 2.38 +/- 1.74; Group 5 5.82 +/- 1.85
• AUC From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) of Esomeprazole After at Least 5 Days of Repeated Dose (Secondary), Mean, μmol*h/L: Group 1 5.53 +/- 3.69; Group 2 3.09 +/- 2.34; Group 3 10.41 +/- 4.55; Group 4 1.99 +/- 1.30; Group 5 5.45 +/- 1.78
• Maximum Plasma Concentration (Cmax) of Esomeprazole After at Least 5 Days of Repeated Dose (Secondary), Mean, μmol/L: Group 1 3.42 +/- 2.09; Group 2 2.09 +/- 1.53; Group 3 5.91 +/- 2.19; Group 4 1.09 +/- 0.57; Group 5 3.13 +/- 1.36
• Time to Reach Maximum Plasma Concentration (Tmax) of Esomeprazole After at Least 5 Days of Repeated Dose (Secondary), Median, hour: Group 1 1.58 (1.03 to 5.92); Group 2 1.52 (0.92 to 6.00); Group 3 1.47 (0.93 to 1.52); Group 4 1.57 (0.93 to 2.95); Group 5 1.75 (0.95 to 3.00)
• 3 more outcome measures not shown.

Adverse events

Time frame: Serious adverse events were collected from the date of signing of informed consent to 8 weeks or withdrawal. Other adverse events were collected from the start of investigational drug administration to 8 weeks or withdrawal.

Serious adverse events by term

Other adverse events by term