Anastomotic Ulcer (AU), Duodenal Ulcer (DU), Gastric Ulcer (GU), Non-erosive Reflux Esophagitis Disease (NERD), Reflux Esophagitis (RE), Zollinger-Ellison Syndrome
Conditions
Keywords
Gastric ulcer (GU), Duodenal ulcer (DU), Anastomotic ulcer (AU), Non-erosive reflux esophagitis disease (NERD), Reflux esophagitis (RE), Zollinger-Ellison syndrome
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.
Interventions
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 14 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 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. |
| 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. |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
Countries
Japan
Participant flow
Recruitment details
First subject enrolled on 24 June 2014 Last subject last visit on 04 April 2016. This study was conducted at a total of 20 sites in Japan.
Pre-assignment details
Out of 55 enrolled subjects, 50 subjects were registered and 5 subjects were not registered. The reason of no registration was 'Did not meet inclusion/exclusion criteria' (5 subjects).
Participants by arm
| Arm | Count |
|---|---|
| Group 1 D961H sachet 10 mg Age: 1-11 years and Weight: \<20 kg | 10 |
| Group 2 D961H capsule 10 mg Age: 1-11 years and Weight: ≥20 kg | 10 |
| Group 3 D961H capsule 20 mg Age: 1-11 years and Weight: ≥20 kg | 10 |
| Group 4 D961H capsule 10 mg Age: 12-14 years and Weight: ≥20 kg | 10 |
| Group 5 D961H capsule 20 mg Age: 12-14 years and Weight: ≥20 kg | 10 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Group 2 | Total | Group 5 | Group 1 | Group 4 | Group 3 |
|---|---|---|---|---|---|---|
| Age, Continuous | 8.9 Years STANDARD_DEVIATION 0.7 | 9.5 Years STANDARD_DEVIATION 3.9 | 13.1 Years STANDARD_DEVIATION 0.9 | 3.6 Years STANDARD_DEVIATION 2.2 | 13.4 Years STANDARD_DEVIATION 0.7 | 8.4 Years STANDARD_DEVIATION 1.8 |
| Age, Customized 10-11 years | 2 Participants | 5 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Age, Customized 12-14 years | 0 Participants | 20 Participants | 10 Participants | 0 Participants | 10 Participants | 0 Participants |
| Age, Customized <= 3 years | 0 Participants | 5 Participants | 0 Participants | 5 Participants | 0 Participants | 0 Participants |
| Age, Customized 4-5 years | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants |
| Age, Customized 6-7 years | 0 Participants | 7 Participants | 0 Participants | 3 Participants | 0 Participants | 4 Participants |
| Age, Customized 8-9 years | 8 Participants | 11 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Gender Female | 6 Participants | 26 Participants | 6 Participants | 5 Participants | 7 Participants | 2 Participants |
| Gender Male | 4 Participants | 24 Participants | 4 Participants | 5 Participants | 3 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 10 | 8 / 10 | 5 / 10 | 5 / 10 | 6 / 10 |
| serious Total, serious adverse events | 2 / 10 | 0 / 10 | 0 / 10 | 0 / 10 | 1 / 10 |
Outcome results
Primary
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.
Time frame: 8 weeks
Population: Participants who had no epigastric pain at pre-dose and were evaluated the symptom at Week 8 by investigators.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Aggravation of Epigastric Pain at Week 8 by Investigators | 0 Participants |
| Group 2 | Aggravation of Epigastric Pain at Week 8 by Investigators | 0 Participants |
| Group 3 | Aggravation of Epigastric Pain at Week 8 by Investigators | 0 Participants |
| Group 4 | Aggravation of Epigastric Pain at Week 8 by Investigators | 0 Participants |
| Group 5 | Aggravation of Epigastric Pain at Week 8 by Investigators | 0 Participants |
Primary
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.
Time frame: 8 weeks
Population: Participants who had no epigastric pain at pre-dose in patient diary and obtained available diary data at Week 8.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Aggravation of Epigastric Pain at Week 8 by Patient Diaries | 0 participants |
| Group 2 | Aggravation of Epigastric Pain at Week 8 by Patient Diaries | 0 participants |
| Group 3 | Aggravation of Epigastric Pain at Week 8 by Patient Diaries | 1 participants |
| Group 4 | Aggravation of Epigastric Pain at Week 8 by Patient Diaries | 1 participants |
| Group 5 | Aggravation of Epigastric Pain at Week 8 by Patient Diaries | 1 participants |
Primary
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.
Time frame: 8 weeks
Population: Participants who had no heartburn at pre-dose and were evaluated the symptom at Week 8 by investigators.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Aggravation of Heartburn at Week 8 by Investigators | 0 Participants |
| Group 2 | Aggravation of Heartburn at Week 8 by Investigators | 0 Participants |
| Group 3 | Aggravation of Heartburn at Week 8 by Investigators | 0 Participants |
| Group 4 | Aggravation of Heartburn at Week 8 by Investigators | 1 Participants |
| Group 5 | Aggravation of Heartburn at Week 8 by Investigators | 0 Participants |
Primary
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.
Time frame: 8 weeks
Population: Participants who had no heartburn at pre-dose in patient diary and obtained available diary data at Week 8.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Aggravation of Heartburn at Week 8 by Patient Diaries | 0 participants |
| Group 2 | Aggravation of Heartburn at Week 8 by Patient Diaries | 0 participants |
| Group 3 | Aggravation of Heartburn at Week 8 by Patient Diaries | 0 participants |
| Group 4 | Aggravation of Heartburn at Week 8 by Patient Diaries | 0 participants |
| Group 5 | Aggravation of Heartburn at Week 8 by Patient Diaries | 0 participants |
Primary
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.
Time frame: 8 weeks
Population: Participants who had no regurgitation at pre-dose and were evaluated the symptom at Week 8 by investigators.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Aggravation of Regurgitation at Week 8 by Investigators | 0 Participants |
| Group 2 | Aggravation of Regurgitation at Week 8 by Investigators | 0 Participants |
| Group 3 | Aggravation of Regurgitation at Week 8 by Investigators | 1 Participants |
| Group 4 | Aggravation of Regurgitation at Week 8 by Investigators | 0 Participants |
| Group 5 | Aggravation of Regurgitation at Week 8 by Investigators | 1 Participants |
Primary
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.
Time frame: 8 weeks
Population: Participants who had no regurgitation at pre-dose in patient diary and obtained available diary data at Week 8.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Aggravation of Regurgitation at Week 8 by Patient Diaries | 2 participants |
| Group 2 | Aggravation of Regurgitation at Week 8 by Patient Diaries | 0 participants |
| Group 3 | Aggravation of Regurgitation at Week 8 by Patient Diaries | 1 participants |
| Group 4 | Aggravation of Regurgitation at Week 8 by Patient Diaries | 0 participants |
| Group 5 | Aggravation of Regurgitation at Week 8 by Patient Diaries | 0 participants |
Primary
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.
Time frame: 8 weeks
Population: Participants who had no upper abdominal discomfort at pre-dose and were evaluated the symptom at Week 8 by investigators.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Aggravation of Upper Abdominal Discomfort at Week 8 by Investigators | 0 Participants |
| Group 2 | Aggravation of Upper Abdominal Discomfort at Week 8 by Investigators | 0 Participants |
| Group 3 | Aggravation of Upper Abdominal Discomfort at Week 8 by Investigators | 0 Participants |
| Group 4 | Aggravation of Upper Abdominal Discomfort at Week 8 by Investigators | 1 Participants |
| Group 5 | Aggravation of Upper Abdominal Discomfort at Week 8 by Investigators | 0 Participants |
Primary
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.
Time frame: 8 weeks
Population: Participants who had no upper abdominal discomfort at pre-dose in patient diary and obtained available diary data at Week 8.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Aggravation of Upper Abdominal Discomfort at Week 8 by Patient Diaries | 0 participants |
| Group 2 | Aggravation of Upper Abdominal Discomfort at Week 8 by Patient Diaries | 0 participants |
| Group 3 | Aggravation of Upper Abdominal Discomfort at Week 8 by Patient Diaries | 2 participants |
| Group 4 | Aggravation of Upper Abdominal Discomfort at Week 8 by Patient Diaries | 1 participants |
| Group 5 | Aggravation of Upper Abdominal Discomfort at Week 8 by Patient Diaries | 0 participants |
Primary
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.
Time frame: 8 weeks
Population: Participants who had an epigastric pain at pre-dose and were evaluated the symptom at Week 8 by investigators.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Disappearance of Epigastric Pain at Week 8 by Investigators | 2 Participants |
| Group 2 | Disappearance of Epigastric Pain at Week 8 by Investigators | 5 Participants |
| Group 3 | Disappearance of Epigastric Pain at Week 8 by Investigators | 4 Participants |
| Group 4 | Disappearance of Epigastric Pain at Week 8 by Investigators | 2 Participants |
| Group 5 | Disappearance of Epigastric Pain at Week 8 by Investigators | 6 Participants |
Primary
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.
Time frame: 8 weeks
Population: Participants who had epigastric pain at pre-dose in patient diary and obtained available diary data at Week 8.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Disappearance of Epigastric Pain at Week 8 by Patient Diaries | 2 Participants |
| Group 2 | Disappearance of Epigastric Pain at Week 8 by Patient Diaries | 3 Participants |
| Group 3 | Disappearance of Epigastric Pain at Week 8 by Patient Diaries | 5 Participants |
| Group 4 | Disappearance of Epigastric Pain at Week 8 by Patient Diaries | 1 Participants |
| Group 5 | Disappearance of Epigastric Pain at Week 8 by Patient Diaries | 3 Participants |
Primary
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.
Time frame: 8 weeks
Population: Participants who had a heartburn at pre-dose and were evaluated the symptom at Week 8 by investigators.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Disappearance of Heartburn at Week 8 by Investigators | 2 Participants |
| Group 2 | Disappearance of Heartburn at Week 8 by Investigators | 1 Participants |
| Group 4 | Disappearance of Heartburn at Week 8 by Investigators | 2 Participants |
| Group 5 | Disappearance of Heartburn at Week 8 by Investigators | 2 Participants |
Primary
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.
Time frame: 8 weeks
Population: Participants who had heartburn at pre-dose in patient diary and obtained available diary data at Week 8.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Disappearance of Heartburn at Week 8 by Patient Diaries | 2 Participants |
| Group 2 | Disappearance of Heartburn at Week 8 by Patient Diaries | 0 Participants |
| Group 3 | Disappearance of Heartburn at Week 8 by Patient Diaries | 0 Participants |
| Group 4 | Disappearance of Heartburn at Week 8 by Patient Diaries | 1 Participants |
| Group 5 | Disappearance of Heartburn at Week 8 by Patient Diaries | 3 Participants |
Primary
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.
Time frame: 8 weeks
Population: Participants who had a regurgitation at pre-dose and were evaluated the symptom at Week 8 by investigators.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Disappearance of Regurgitation at Week 8 by Investigators | 3 Participants |
| Group 2 | Disappearance of Regurgitation at Week 8 by Investigators | 0 Participants |
| Group 3 | Disappearance of Regurgitation at Week 8 by Investigators | 3 Participants |
| Group 4 | Disappearance of Regurgitation at Week 8 by Investigators | 1 Participants |
| Group 5 | Disappearance of Regurgitation at Week 8 by Investigators | 3 Participants |
Primary
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.
Time frame: 8 weeks
Population: Participants who had regurgitation at pre-dose in patient diary and obtained available diary data at Week 8.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Disappearance of Regurgitation at Week 8 by Patient Diaries | 3 Participants |
| Group 2 | Disappearance of Regurgitation at Week 8 by Patient Diaries | 2 Participants |
| Group 3 | Disappearance of Regurgitation at Week 8 by Patient Diaries | 3 Participants |
| Group 4 | Disappearance of Regurgitation at Week 8 by Patient Diaries | 2 Participants |
| Group 5 | Disappearance of Regurgitation at Week 8 by Patient Diaries | 4 Participants |
Primary
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.
Time frame: 8 weeks
Population: Participants who had an upper abdominal discomfort at pre-dose and were evaluated the symptom at Week 8 by investigators.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Disappearance of Upper Abdominal Discomfort at Week 8 by Investigators | 3 Participants |
| Group 2 | Disappearance of Upper Abdominal Discomfort at Week 8 by Investigators | 5 Participants |
| Group 3 | Disappearance of Upper Abdominal Discomfort at Week 8 by Investigators | 4 Participants |
| Group 4 | Disappearance of Upper Abdominal Discomfort at Week 8 by Investigators | 4 Participants |
| Group 5 | Disappearance of Upper Abdominal Discomfort at Week 8 by Investigators | 3 Participants |
Primary
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.
Time frame: 8 weeks
Population: Participants who had upper abdominal discomfort at pre-dose in patient diary and obtained available diary data at Week 8.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Disappearance of Upper Abdominal Discomfort at Week 8 by Patient Diaries | 3 Participants |
| Group 2 | Disappearance of Upper Abdominal Discomfort at Week 8 by Patient Diaries | 2 Participants |
| Group 3 | Disappearance of Upper Abdominal Discomfort at Week 8 by Patient Diaries | 4 Participants |
| Group 4 | Disappearance of Upper Abdominal Discomfort at Week 8 by Patient Diaries | 2 Participants |
| Group 5 | Disappearance of Upper Abdominal Discomfort at Week 8 by Patient Diaries | 2 Participants |
Secondary
Apparent Total Clearance (CL/F) of Esomeprazole After at Least 5 Days of Repeated Dose
Time frame: 0, 0.5, 1, 1.5, 2, 3, 4 and 6 hours post-dose after at least 5 days of repeated dose
Population: All patients who had at least one plasma concentration data after administration of study drug without any protocol deviations that would have an impact on the PK.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 | Apparent Total Clearance (CL/F) of Esomeprazole After at Least 5 Days of Repeated Dose | 4.74 L/h | Standard Deviation 1.92 |
| Group 2 | Apparent Total Clearance (CL/F) of Esomeprazole After at Least 5 Days of Repeated Dose | 12.44 L/h | Standard Deviation 8.9 |
| Group 3 | Apparent Total Clearance (CL/F) of Esomeprazole After at Least 5 Days of Repeated Dose | 6.44 L/h | Standard Deviation 3.37 |
| Group 4 | Apparent Total Clearance (CL/F) of Esomeprazole After at Least 5 Days of Repeated Dose | 23.33 L/h | Standard Deviation 24.93 |
| Group 5 | Apparent Total Clearance (CL/F) of Esomeprazole After at Least 5 Days of Repeated Dose | 10.94 L/h | Standard Deviation 3.64 |
Secondary
Apparent Volume of Distribution (Vz/F) of Esomeprazole After at Least 5 Days of Repeated Dose
Time frame: 0, 0.5, 1, 1.5, 2, 3, 4 and 6 hours post-dose after at least 5 days of repeated dose
Population: All patients who had at least one plasma concentration data after administration of study drug without any protocol deviations that would have an impact on the PK.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 | Apparent Volume of Distribution (Vz/F) of Esomeprazole After at Least 5 Days of Repeated Dose | 5.10 L | Standard Deviation 1.24 |
| Group 2 | Apparent Volume of Distribution (Vz/F) of Esomeprazole After at Least 5 Days of Repeated Dose | 16.56 L | Standard Deviation 16.21 |
| Group 3 | Apparent Volume of Distribution (Vz/F) of Esomeprazole After at Least 5 Days of Repeated Dose | 9.21 L | Standard Deviation 4 |
| Group 4 | Apparent Volume of Distribution (Vz/F) of Esomeprazole After at Least 5 Days of Repeated Dose | 44.73 L | Standard Deviation 72.03 |
| Group 5 | Apparent Volume of Distribution (Vz/F) of Esomeprazole After at Least 5 Days of Repeated Dose | 15.90 L | Standard Deviation 4.42 |
Secondary
Area Under the Plasma Concentration-time Curve During a Dosing Interval (AUCtau) of Esomeprazole After at Least 5 Days of Repeated Dose
Time frame: 0, 0.5, 1, 1.5, 2, 3, 4 and 6 hours post-dose after at least 5 days of repeated dose
Population: All patients who had at least one plasma concentration data after administration of study drug without any protocol deviations that would have an impact on the pharmacokinetics (PK).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 | Area Under the Plasma Concentration-time Curve During a Dosing Interval (AUCtau) of Esomeprazole After at Least 5 Days of Repeated Dose | 7.04 μmol*h/L | Standard Deviation 3.05 |
| Group 2 | Area Under the Plasma Concentration-time Curve During a Dosing Interval (AUCtau) of Esomeprazole After at Least 5 Days of Repeated Dose | 3.52 μmol*h/L | Standard Deviation 2.35 |
| Group 3 | Area Under the Plasma Concentration-time Curve During a Dosing Interval (AUCtau) of Esomeprazole After at Least 5 Days of Repeated Dose | 11.05 μmol*h/L | Standard Deviation 5.11 |
| Group 4 | Area Under the Plasma Concentration-time Curve During a Dosing Interval (AUCtau) of Esomeprazole After at Least 5 Days of Repeated Dose | 2.38 μmol*h/L | Standard Deviation 1.74 |
| Group 5 | Area Under the Plasma Concentration-time Curve During a Dosing Interval (AUCtau) of Esomeprazole After at Least 5 Days of Repeated Dose | 5.82 μmol*h/L | Standard Deviation 1.85 |
Secondary
AUC From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) of Esomeprazole After at Least 5 Days of Repeated Dose
Time frame: 0, 0.5, 1, 1.5, 2, 3, 4 and 6 hours post-dose after at least 5 days of repeated dose
Population: All patients who had at least one plasma concentration data after administration of study drug without any protocol deviations that would have an impact on the PK.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 | AUC From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) of Esomeprazole After at Least 5 Days of Repeated Dose | 5.53 μmol*h/L | Standard Deviation 3.69 |
| Group 2 | AUC From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) of Esomeprazole After at Least 5 Days of Repeated Dose | 3.09 μmol*h/L | Standard Deviation 2.34 |
| Group 3 | AUC From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) of Esomeprazole After at Least 5 Days of Repeated Dose | 10.41 μmol*h/L | Standard Deviation 4.55 |
| Group 4 | AUC From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) of Esomeprazole After at Least 5 Days of Repeated Dose | 1.99 μmol*h/L | Standard Deviation 1.3 |
| Group 5 | AUC From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) of Esomeprazole After at Least 5 Days of Repeated Dose | 5.45 μmol*h/L | Standard Deviation 1.78 |
Secondary
Elimination Half-life (t1/2) of Esomeprazole After at Least 5 Days of Repeated Dose
Time frame: 0, 0.5, 1, 1.5, 2, 3, 4 and 6 hours post-dose after at least 5 days of repeated dose
Population: All patients who had at least one plasma concentration data after administration of study drug without any protocol deviations that would have an impact on the PK.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 | Elimination Half-life (t1/2) of Esomeprazole After at Least 5 Days of Repeated Dose | 0.80 hour | Standard Deviation 0.18 |
| Group 2 | Elimination Half-life (t1/2) of Esomeprazole After at Least 5 Days of Repeated Dose | 0.97 hour | Standard Deviation 0.55 |
| Group 3 | Elimination Half-life (t1/2) of Esomeprazole After at Least 5 Days of Repeated Dose | 1.08 hour | Standard Deviation 0.44 |
| Group 4 | Elimination Half-life (t1/2) of Esomeprazole After at Least 5 Days of Repeated Dose | 1.37 hour | Standard Deviation 0.88 |
| Group 5 | Elimination Half-life (t1/2) of Esomeprazole After at Least 5 Days of Repeated Dose | 1.06 hour | Standard Deviation 0.25 |
Secondary
Maximum Plasma Concentration (Cmax) of Esomeprazole After at Least 5 Days of Repeated Dose
Time frame: 0, 0.5, 1, 1.5, 2, 3, 4 and 6 hours post-dose after at least 5 days of repeated dose
Population: All patients who had at least one plasma concentration data after administration of study drug without any protocol deviations that would have an impact on the PK.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 | Maximum Plasma Concentration (Cmax) of Esomeprazole After at Least 5 Days of Repeated Dose | 3.42 μmol/L | Standard Deviation 2.09 |
| Group 2 | Maximum Plasma Concentration (Cmax) of Esomeprazole After at Least 5 Days of Repeated Dose | 2.09 μmol/L | Standard Deviation 1.53 |
| Group 3 | Maximum Plasma Concentration (Cmax) of Esomeprazole After at Least 5 Days of Repeated Dose | 5.91 μmol/L | Standard Deviation 2.19 |
| Group 4 | Maximum Plasma Concentration (Cmax) of Esomeprazole After at Least 5 Days of Repeated Dose | 1.09 μmol/L | Standard Deviation 0.57 |
| Group 5 | Maximum Plasma Concentration (Cmax) of Esomeprazole After at Least 5 Days of Repeated Dose | 3.13 μmol/L | Standard Deviation 1.36 |
Secondary
Time to Reach Maximum Plasma Concentration (Tmax) of Esomeprazole After at Least 5 Days of Repeated Dose
Time frame: 0, 0.5, 1, 1.5, 2, 3, 4 and 6 hours post-dose after at least 5 days of repeated dose
Population: All patients who had at least one plasma concentration data after administration of study drug without any protocol deviations that would have an impact on the PK.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Group 1 | Time to Reach Maximum Plasma Concentration (Tmax) of Esomeprazole After at Least 5 Days of Repeated Dose | 1.58 hour | Full Range 2.09 |
| Group 2 | Time to Reach Maximum Plasma Concentration (Tmax) of Esomeprazole After at Least 5 Days of Repeated Dose | 1.52 hour | Full Range 1.53 |
| Group 3 | Time to Reach Maximum Plasma Concentration (Tmax) of Esomeprazole After at Least 5 Days of Repeated Dose | 1.47 hour | Full Range 2.19 |
| Group 4 | Time to Reach Maximum Plasma Concentration (Tmax) of Esomeprazole After at Least 5 Days of Repeated Dose | 1.57 hour | Full Range 0.57 |
| Group 5 | Time to Reach Maximum Plasma Concentration (Tmax) of Esomeprazole After at Least 5 Days of Repeated Dose | 1.75 hour | Full Range 1.36 |