Clinical Trials Register

Summary
EudraCT Number:	2012-001157-97
Sponsor's Protocol Code Number:	D9614C00099
Clinical Trial Type:	Outside EU/EEA
Date on which this record was first entered in the EudraCT database:	2012-03-08
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED

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A. Protocol Information

A.2

EudraCT number

2012-001157-97

A.3

Full title of the trial

A Randomized, Open-Label Study to Evaluate the Pharmacokinetics of Multiple Doses of Esomeprazole Magnesium in a Pediatric Population of 1 to 11 Year olds with Gastroesophageal Reflux Disease (GERD) or Symptoms of GERD

A.4.1

Sponsor's protocol code number

D9614C00099

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/209/2009

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	AstraZeneca AB
B.1.3.4	Country	Sweden
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AstraZeneca
B.5.2	Functional name of contact point	Information Center
B.5.6	E-mail	information.center@astrazeneca.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	esomeprazol
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	217087-09-7
D.3.9.3	Other descriptive name	ESOMEPRAZOLE MAGNESIUM
D.3.9.4	EV Substance Code	SUB16427MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	esomeprazol
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	217087-09-7
D.3.9.3	Other descriptive name	ESOMEPRAZOLE MAGNESIUM
D.3.9.4	EV Substance Code	SUB16427MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	esomeprazol
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	217087-09-7
D.3.9.3	Other descriptive name	ESOMEPRAZOLE MAGNESIUM
D.3.9.4	EV Substance Code	SUB16427MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

The target subject population was male and female children, aged 1 to 11 years inclusive, who suffered from GERD or symptoms of GERD and were candidates for acid suppression therapy.

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10017885
E.1.2	Term	Gastrooesophageal reflux disease
E.1.2	System Organ Class	10017947 - Gastrointestinal disorders

E.1.3

Condition being studied is a rare disease

Information not present in EudraCT

E.2 Objective of the trial

E.2.1

Main objective of the trial

Primary Objective: To determine the area under the curve (AUC) of esomeprazole after multiple oral doses of 5 mg, 10 mg, and 20 mg esomeprazole magnesium in 1 to 11 year olds, inclusive with GERD or symptoms of GERD.

E.2.2

Secondary objectives of the trial

Secondary Objectives:
• To determine the AUC(0-t), Cmax, tmax, t½z, apparent oral clearance (CL/F), apparent volume of distribution during terminal phase (Vz/F) and apparent volume of distribution at steady state (Vss/F) of esomeprazole after multiple oral doses of 5 mg, 10 mg, and 20 mg esomeprazole in 1 to 11 year olds, inclusive with GERD or symptoms of GERD.
• To determine AUC, AUC(0-t), Cmax, tmax, t½z of the 5-hydroxy and sulphone metabolites of esomeprazole after multiple oral doses of 5 mg, 10 mg, and 20 mg esomeprazole magnesium in 1 to 11 year olds, inclusive with GERD or symptoms of GERD. (Note: The PK parameters of the 5-hydroxy metabolite were not determined because it could not be separated from the 3-hydroxy metabolite on the HPLC chromatogram.)
• To assess the safety and tolerability of esomeprazole in 1 to 11 year olds, inclusive with GERD or symptoms of GERD.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Provision of signed, written informed consent from subject’s parent/guardian with assent from the subject if appropriate.
2. Subjects, both male and female, between the ages of 1 and 11 inclusive.
3. Subjects must have had a clinical diagnosis of GERD made by the investigator based on any of the following factors: history, physical examination, symptoms identified during review of systems. Laboratory test results or information in the previous 6 months from diagnostic testing such as pH probe monitoring, scintigraphy or endoscopy was acceptable if the subject was symptomatic. Notes in the subject’s medical records and/or other source documentation were used to support the diagnosis.
4. Subjects were able to take solid food (eg, applesauce) and were of sufficient weight (at least 10 kg or 22 lb) to allow for an adequate volume of blood to be collected.
5. Post-pubertal female subjects must have had a negative urine pregnancy test at screening and prior to study drug administration on Days 1 and 5.
6. Subjects were able to tolerate discontinuation of their PPI therapy for 7 days and/or H2RA therapy for 3 days prior to the first dose of study drug and throughout the study.

E.4

Principal exclusion criteria

1. Use of any other investigational compound or participation in another clinical trial within 28 days prior to the screening visit.
2. Female subjects who were pregnant, wished to become pregnant during the study, or were lactating.
3. Female subjects who were taking a systemic hormonal contraceptive (eg, oral, parenteral, patch).
4. History or presence of gastrointestinal, hepatic, or renal disease or other condition that could have interfered with absorption, distribution, metabolism or excretion of esomeprazole.
5. Unstable diabetes mellitus or history of a seizure disorder.
6. Any acute or chronic illness or a medical history, which in the opinion of the investigator, could have compromised the subject’s safety or successful participation in the study.
7. History of multiple drug allergies unless otherwise agreed by AstraZeneca and the investigator.
8. Hypersensitivity, allergy, or intolerance to esomeprazole, any ingredient in its formulation or any drug with a similar chemical structure to esomeprazole.
9. Concurrent use of anti-epileptic medications phenytoin, mephenytoin, antineoplastic agents, pro-motility drugs (prokinetics), sucralfate or Warfarin.
10. Use of any drug known to affect the PK parameters of esomeprazole within 14 days prior to the first dose of study drug (Day 1). These drugs included, but were not limited to, enzyme inducers such as phenobarbital, carbamazepine, rifampicin, and St. John’s Wort, or enzyme inhibitors such as clarithromycin, erythromycin, SSRIs, cimetidine, itraconazole, protease inhibitors, and ketaconazole.
11. Clinically significant abnormal values at screening from the laboratory measurements, physical examination, or vital signs which, in the opinion of the investigator, could have put the subject at risk when participating in the study (other than those directly related to some concurrent and stable disease) or if the values from laboratory measurements were both unexplained and potentially significant.

E.5 End points

E.5.1

Primary end point(s)

Pharmacokinetic: Blood samples were analyzed to determine the pharmacokinetics of esomeprazole magnesium (AUC, AUC(0-t), Cmax, tmax, t½z, CL/F, Vz/F and Vss/F) and the pharmacokinetics of its sulphone metabolite (AUC, AUC(0-t), Cmax, tmax, t½z) in the specified population.
Safety: Safety and tolerability were assessed by means of incidence and severity of all adverse events, vital signs, laboratory parameters and physical examinations.

E.5.1.1

Timepoint(s) of evaluation of this end point

The final dose of study drug was administered on the morning of Day 5 and PK was measured.
Fourteen or 15 days after Day 5, all subjects/parents/guardians received a follow-up telephone call from the CRC. Information was collected regarding any AE (adverse event) resolution and/or potential SAEs (serious adverse events) that occurred.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

Will this trial be conducted at a single site globally?

Yes

E.8.4

Will this trial be conducted at multiple sites globally?

E.8.6 Trial involving sites outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Yes

E.8.6.3

Specify the countries outside of the EEA in which trial sites are planned

United States

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

E.8.9 Initial estimate of the duration of the trial

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

Yes

F.1.1.4.1

Number of subjects for this age range:

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Provision of signed, written informed consent from subject’s parent/guardian with assent from the subject if appropriate

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.2

For a multinational trial

F.4.2.2

In the whole clinical trial

G. Investigator Networks to be involved in the Trial

H.4 Third Country in which the Trial was first authorised
H.4.1	Third Country in which the trial was first authorised:	United States

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