A Phase I, Randomized, 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

• Conditions: Patients, aged 0-17 years, with a presumptive diagnosis of GERD, a clinical diagnosis of suspected GERD, symptomatic GERD, or endoscopically proven GERD.; MedDRA version: 14.1Level: PTClassification code 10017885Term: Gastrooesophageal reflux diseaseSystem Organ Class: 10017947 - Gastrointestinal disorders; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2007-000628-41-Outside-EU/EEA
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-03-09
• Last Update Posted: 20 March 2012

Recruitment & Eligibility

• Status: A
• Sex: All
• Target Recruitment: 84

Inclusion Criteria

1. Provision of signed, written informed consent from the patient’s parent/guardian.
2. Patients who are able to comprehend their involvement in a clinical study, including
the risks and benefits (typically =6 years old), must have assent documented, as
appropriate, by study personnel prior to any study-related procedures. 3. Female and/or male hospitalized patients aged 0 to 17 years old. 4. Patients, who are considered, in the judgement of the investigator, to be a candidate for acid suppression therapy treatment, including, but not limeted to patients with a presumptive diagnosis of GERD, a clinical diagnosis of suspected GERD, symptomatic GERD, or endoscopically proven GERD. 5. Patients must weigh at least 1.5 kilograms (kg). 6. For patients 2 to 17 years old, Body Mass Index (BMI) should be calculated and must be between the 5th and 95th percentile for age at inclusion and patients 0 and up to 2 years old, weight and height should be plotted on a standard weight for stature curve, and must be between the 5th and 95th percentile at inclusion. 7. Post-menarchal females must have a negative urine pregnancy test prior to randomisation.
Are the trial subjects under 18? yes
Number of subjects for this age range: 67
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Any of the following is regarded as a criterion for exclusion from the study:
1. Involvement in the planning and conduct of the study (applies to both AstraZeneca
staff, staff at the study site, and parents/caretakers) 2. Previous enrolment or randomisation of treatment in the present study 3. Unstable diabetes mellitus. 4. Participation in a clinical study during 28 days prior to the screening visit. Patients who have used investigational devices or products that are not systemically absorbed within 28 days prior to the screening visit should be considered for entry into the study on a case-by-case basis, and discussed with the Sponsor prior to study enrolment. 5. Concomitant use of other PPIs during the treatment with the investigational product. PPIs are allowed up to but not including the day of randomization. 6. Concomitant use of digoxin or iron salts during the treatment with the investigational product. Digoxin and iron salets aare allowed up to but not including the day of randomization. 7.Use of any drug known to affect the PK parameters of esomeprazole within 14 days prior to administration of investigational product on Day 1. A single dose of an excluded medication is allowed up to 7 days prior to administration of study drug on Day 1. These drugs include, but are not limited to the following:
- enzyme (cytochrome P450) inducers such as phenobarbital (3A inducer), carbamazepine (2C19 & 3A inducer), rifampicin (3A inducer), and St. John’s Wort (3A inducer) - enzyme (cytochrome P450) inhibitors such as clarithromycin (3A inhibitor),
erythromycin (3A inhibitor), Selective Serotonin Reuptake Inhibitors [(SSRIs) 3A and 2C19 inhibitors], cimetidine (3A and 2C19 inhibitor), itraconazole (3A inhibitors), protease inhibitors (3A4 inhibitors/inducers), and ketaconazole (3A and 2C19 inhibitor). 8. Patients with a history of multiple drug allergies unless otherwise agreed by Investigator and AstraZeneca. 9. Hypersensitivity, allergy, or intolerance to any PPI, any ingredient in any PPI’s formulation, or any drug with a similar chemical structure to any PPI. 10. Any condition that, in the judgement of the investigator, would make performance of any study procedures unsafe, or which would make it unlikely that the patient would complete the study and all study procedures. 11. Any acute or chronic illness or a medical history, which in the opinion of the Investigator and/or Sponsor, could compromise the patient’s safety or successful participation in the study, such as: o- History of severe liver disease, including (but not limited to) cirrhosis and acute or chronic hepatitis. Liver enzymes (AST, ALT, or alkaline phosphatase) or total bilirubin 3 times the upper normal limit, and confirmed by repeat testing that may represent hepatic dysfunction. Benign elevations allowed (eg. Gilbert’s Syndrome and neonatal hyperbilirubinemia).
-Severe renal disease, including chronic renal disease or impaired renal function
as manifested by any of the following: serum creatinine outside age adjusted
local normative values, or markedly abnormal urine sediment on repeated
examination as judged by the Investigator. - Generalized bleeding disorder (such as abnormalities in clotting factors or platelets), as judged by the Investigator.
11. Significant cardiac abnormalities (e.g. septal defects) which are expected to significally affect the pharmacokinetics of esomprazole (e.g. elevated pulmonary to systemic flor ratios). 12. Clinic

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective is to evaluate the pharmacokinetics of repeated doses of esomeprazole given as an once daily (qd) injection over 3 minutes in paediatric patients 0 to 17 years old, inclusive, by assessment of the total area under the plasma concentration versus time curve within a dosing interval (AUCt) on Day 4 of the study based on population PK modelling.<br>;Secondary Objective: •To evaluate the pharmacokinetics of the main metabolites of esomeprazole (sulphone metabolite and 5-hydroxy metabolite) after repeated doses of esomeprazole given as a once daily injection over 3 minutes in pediatric patients 0 to 17 years old, inclusive.<br>•To evaluate the safety;Primary end point(s): AUCt for esomeprazole on Day 4 of the study;Timepoint(s) of evaluation of this end point: Day 4 of the study

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): PK sekundary objectives: AUCt, Css, max, CL/fm, and Vss/fm on Day 4 of the study for the esomeprazole sulphone metabolite and esomeprazole 5-hydroxy metabolite<br>Safety: by assessment of adverse events (AEs), laboratory values, blood pressure, heart rate, respiratory rate, body temperature, and electrocardiogram (ECG).;Timepoint(s) of evaluation of this end point: PK evaluation on Day 4 of the study.<br>Safety evaluated during the 4 days treatment period and up to the follow-up visit, 28 days post last dosing.