Phase 1 Pharmacokinetics of Intravenous Nexium in Children

A Phase I, Randomised, Open-label, Multi-National Study to Evaluate the Pharmacokinetics of Repeated Once-Daily Intravenous Doses of Esomeprazole in Paediatric Patients 0 to 17 Years Old, Inclusive.

The purpose of this research study is to evaluate how much of repeated once daily intravenous (IV, meaning through a vein) doses of esomeprazole gets into the bloodstream of hospitalized children aged 0-17 years old that require acid suppression therapy.

Study Overview

• Status: Completed
• Conditions: Pharmacokinetics
• Intervention / Treatment: Drug: esomeprazole

• Study Type: Interventional
• Enrollment (Anticipated): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • North Adelaide, South Australia, Australia
      • Research Site
• Belgium
  • Brussels (jette), Belgium
    • Research Site
• Hungary
  • Budapest, Hungary
    • Research Site
• Sweden
  • Goteborg, Sweden
    • Research Site
• United States
  • Arkansas
    • Little Rock, Arkansas, United States
      • Research Site
  • Connecticut
    • Hartford, Connecticut, United States
      • Research Site
  • Illinois
    • Park Ridge, Illinois, United States
      • Research Site
  • Kentucky
    • Louisville, Kentucky, United States
      • Research Site
  • Michigan
    • Detroit, Michigan, United States
      • Research Site
    • Southfield, Michigan, United States
      • Research Site
  • New Jersey
    • New Brunswick, New Jersey, United States
      • Research Site
  • New York
    • Buffalo, New York, United States
      • Research Site
  • Ohio
    • Cleveland, Ohio, United States
      • Research Site
  • Texas
    • Fort Worth, Texas, United States
      • Research Site
    • Houston, Texas, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• parent/guardian must sign consent form and the child will be asked to sign and Assent Form if he/she is old enough and is able to sign
• verbal assent will be acceptable if the child is old enough to understand, but unable to write
• female and/or male hospitalized patients aged 0-17 years old who should be considered for treatment with acid suppressive therapy.

Exclusion Criteria:

• female patients that are pregnant, or plan to become pregnant during the study period or is breast-feeding a child
• patients with a history of multiple drug allergies
• any illness, medical history, abnormal laboratory values, abnormal physical examination findings or abnormal vitals signs that could put the patient at risk when participating in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Based on age and/or weight dose of esomeprazole IV qd in milligrams 20,40,10,20,10, 1.0 mg/kg, 0,5 mg/kg	Drug: esomeprazole; IV qd for 4 days; Other Names: Nexium

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetic-area under plasma concentration versus time curve within a dosing interval	Day 4 of study

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum plasma concentration, total, plasma clearance, steady-state volume of distribution of esomeprazole	Day 4 of study
Safety and tolerability will be assessed by AEs, laboratory values, blood pressure, heart rate, respiratory rate, body temperature, and ECG	Days 1-4 (during treatment), Days 1-28 (post treatment)
Evaluate main metabolites of esomeprazole (sulphone metabolite and 5-hydroxy metabolite) by assessment of max plasma conc, total area under the plasma concentration vs time curve within a dosing interval, clearance scaled by fraction metabolised	Day 4

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Kurt Brown, MD, AstraZeneca; Study Director: Per Lundborg, MD, AstraZeneca; Study Director: Jill McGuinn, AstraZeneca

Publications and helpful links

General Publications

• Earp JC, Mehrotra N, Peters KE, Fiorentino RP, Griebel D, Lee SC, Mulberg A, Rohss K, Sandstrom M, Taylor A, Tornoe CW, Wynn EL, Van der Walt JS, Garnett C. Esomeprazole FDA Approval in Children With GERD: Exposure-Matching and Exposure-Response. J Pediatr Gastroenterol Nutr. 2017 Sep;65(3):272-277. doi: 10.1097/MPG.0000000000001467.
• Sandstrom M, Davidson G, Tolia V, Sullivan JE, Langstrom G, Lundborg P, Brown K. Phase I, multicenter, randomized, open-label study evaluating the pharmacokinetics and safety profile of repeated once-daily doses of intravenous esomeprazole in children 0 to 17 years of age. Clin Ther. 2012 Aug;34(8):1828-38. doi: 10.1016/j.clinthera.2012.06.028. Epub 2012 Jul 24.

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: May 14, 2007
• First Submitted That Met QC Criteria: May 14, 2007
• First Posted (Estimate): May 16, 2007

Study Record Updates

• Last Update Posted (Estimate): December 3, 2010
• Last Update Submitted That Met QC Criteria: December 2, 2010
• Last Verified: December 1, 2010

More Information

Terms related to this study

• Keywords: pediatrics; neonates
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Esomeprazole
• Other Study ID Numbers: D9615C00021