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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: 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

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 Summary:
Sponsor: AstraZeneca

Current Primary Outcome:

  • Disappearance of Heartburn at Week 8 by Patient Diaries [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 8 weeks ]
    The disappearance of regurgitation was assessed by the intensi

    Original Primary Outcome: Safety of D961H in terms of a panel of safety measures: adverse events, physical examination, vital signs and laboratory variables [ Time Frame: From baseline to 8 weeks ]

    Current Secondary Outcome:

    • 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 ]
    • 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 ]
    • 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 ]
    • 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 ]
    • 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 ]
    • 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 ]
    • 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 ]


    Original Secondary Outcome:

    • Pharmacodynamic variabilities by assessment of the percentages of time with intragastric pH >4 and pH>3 (percent of the time) [ Time Frame: Pre dose (Week 0) and after at least 5 days of repeated dose (Week 1,4 or 8) ]
    • Pharmacokinetics of esomeprazole and its metabolites by assessment of AUCtau, AUC0-t, Cmax, tmax, t½, CL/F and Vz/F [ Time Frame: Pre dose (Week 0) and after at least 5 days of repeated dose (Week 1,4 or 8) ]
      AUCtau, AUC0-t, Cmax, tmax, and t1/2 (For all) CL/F, Vz/F (For esomeprazole only) AUCtau:Area under the curve during a dosing interval, AUC0-t:AUC from time zero to time of last quantifiable concentration, Cmax:Maximum plasma concentration,tmax: Time to reach maximum plasma concentration, t½: Elimination half-life, CL/F: Apparent total clearance and Vz/F: Apparent volume of distribution during terminal phase
    • The number of disappearance or aggravation of gastrointestinal symptom assessed by the investigators and the patient diaries [ Time Frame: From baseline to 8 weeks ]
    • Pharmacodynamic variabilities by assessment of median intragastric pH during 12 hours [ Time Frame: Pre dose (Week 0) and after at least 5 days of repeated dose (Week 1,4 or 8) ]
    • The percentage of disappearance or aggravation of gastrointestinal symptom assessed by the investigators and the patient diaries [ Time Frame: From baseline to 8 weeks ]


    Information By: AstraZeneca

    Dates:
    Date Received: May 30, 2014
    Date Started: June 2014
    Date Completion:
    Last Updated: November 28, 2016
    Last Verified: November 2016