Clinical Trials Register

Summary
EudraCT Number:	2013-005323-17
Sponsor's Protocol Code Number:	AML02
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2014-05-26
Trial 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
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Netherlands - Competent Authority

A.2

EudraCT number

2013-005323-17

A.3

Full title of the trial

Pharmacokinetic and pharmacodynamic properties of amlodipine oral solution in the pediatric population

Farmacokinetische en farmacodynamische eigenschappen van amlodipine orale oplossing bij de pediatrische populatie

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Action of amlodipine oral solution in children

Toepassing van amlodipinedrank bij kinderen

A.3.2

Name or abbreviated title of the trial where available

PK-PD of amlodipine in children

PK-PD van amlodipine bij kinderen

A.4.1

Sponsor's protocol code number

AML02

A.5.4

Other Identifiers

Name:

NTR Number

Number:

NTR 47653

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Erasmus MC
B.1.3.4	Country	Netherlands
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	ZonMW
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Erasmus MC
B.5.2	Functional name of contact point	Erasmus MC-Sophia Hospital Pharmacy
B.5.3	Address:
B.5.3.1	Street Address	Dr. Molewaterplein 60
B.5.3.2	Town/ city	Rotterdam
B.5.3.3	Post code	3015 GJ
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	00310107033202
B.5.6	E-mail	l.hanff@erasmusmc.nl

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	Amlodipine oral solution 0.5 mg/ml
D.3.4	Pharmaceutical form	Oral solution
D.3.4.1	Specific paediatric formulation	Yes
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	amlodipine
D.3.9.3	Other descriptive name	AMLODIPINE BESILATE
D.3.9.4	EV Substance Code	SUB12864MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.5
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.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

Hypertension

Hypertensie

E.1.1.1

Medical condition in easily understood language

High blood pressure

Hoge bloeddruk

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of this study is to characterize the pharmacokinetic properties (clearance (Cl), volume of distribution (Vd), and absorption rate constant (ka)) of amlodipine using the newly developed amlodipine oral solution 0.5 mg/ml in patients with chronic kidney diseases (CKD) and hypertension aged 6 months to <12 years using a population pharmacokinetic study design.

Het doel van deze studie is om de farmacokinetische eigenschappen (klaring (Cl), verdelingsvolume (Vd), en absorptieconstante (ka)) van amlodipine orale oplossing 0.5 mg/ml in patiënten van 6 maanden tot 12 jaar met chronische nierziekten te bepalen met behulp van een populatie farmacokinetiek onderzoeksopzet.

E.2.2

Secondary objectives of the trial

•To evaluate the safety of amlodipine oral solution 0.5 mg/ml.
•To assess the effect of the once and twice daily dosing regimen of amlodipine on SBP and DBP and amlodipine plasma concentrations.
•To assess the taste of amlodipine oral solution 0.5 mg/ml.
•To assess the preference of amlodipine formulation of children and their parents.

•Het evalueren van de veiligheid van amlodipine orale oplossing 0.5 mg/ml.
•Het bepalen van het effect van éénmaal en tweemaal daags doseren van amlodipine op de SBD en DBD en amlodipine bloedspiegels.
•Het bepalen van de smaak van amlodipine orale oplossing 0.5 mg/ml.
•Het bepalen van de voorkeur van kinderen en hun ouders voor de toedieningsvorm van amlodipine.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Age between 6 months and <12 years, signed consent from the parent or legal assent, ongoing treatment with amlodipine at the same dosage for at least 2 weeks, a normal BP defined as mean SBP and DBP that is less than the 90th percentile for sex, age and height (1), no anticipated change in use of amlodipine or other antihypertensive medication, and use of the CYP3A4 inhibitor telaprevir and other antihypertensive agents should be at a fixed dosage for at least 2 weeks prior to the study. Renal transplant patients should have had their transplantation at least 4 months prior to recruitment.

Leeftijd tussen 6 maanden en 12 jaar, getekende toestemmingsverklaring door ouders/verzorgers, behandeling met amlodipine in dezelfde dosering voor gedurende tenminste 2 weken voorafgaand aan het onderzoek, een normale bloeddruk die gedefinieerd is als een gemiddelde SBD en DBD die minder is dan het 90ste percentiel voor geslacht, leeftijd en lengte, geen geplande verandering in gebruik van amlodipine of andere antihypertensiva, en de doseringen van de CYP3A4 remmer teleprevir en andere antihypertensiva moeten tenminste gedurende 2 weken vooraf aan het onderzoek constant zijn gebleven. Patiënten met een donornier moeten deze tenminste 4 maanden voor aanvang van het onderzoek hebben ontvangen.

E.4

Principal exclusion criteria

Concomitant treatment with another investigational drug within 1 month prior to study entry, transient, unstable, malignant, or accelerated hypertension, poor vascular access, history of noncompliance, allergy to one of the compounds of the investigational product, or one of the contraindications of amlodipine use (hypersensitivity to dihydropyridine derivatives, severe hypotension, shock (including cardiogenic shock), obstruction of the outflow tract of the left ventricle (e.g. aortic stenosis), hemodynamically unstable heart failure after acute myocardial infarction).

Gelijktijdig gebruik van een ander onderzoeksgeneesmiddel binnen 1 maand voorafgaand aan de studie, tijdelijke, instabiele, maligne, of verergerde hypertensive, slechte toegang tot het bloedvatenstelsel, bekend met therapie ontrouw, allergie voor een van de bestanddelen van het onderzoeksgeneesmiddel, of een van de contra-indicaties van amlodipine (overgevoeligheid voor dihydropyridine derivaten, ernstige hypotensie, schock (inclusief cardiale shock), obstructive van het uitgaande bloedvat uit de linker ventrikel (ofwel stenose van de aorta), hemodynamisch instabiel hartfalen na een acuut myocard infarct).

E.5 End points

E.5.1

Primary end point(s)

Pharmacokinetic parameters Cl, Vd, and ka of amlodipine using the newly developed amlodipine oral solution 0.5 mg/ml.

Farmacokinetische parameters Cl, Vd, en ka van amlodipine orale oplossing 0.5 mg/ml.

E.5.1.1

Timepoint(s) of evaluation of this end point

All pharmacokinetic parameters will be evaluated after completion of the
study.

Alle farmacokinetische parameters zullen geevalueerd worden nadat het
onderzoek voltooid is.

E.5.2

Secondary end point(s)

•The safety of amlodipine oral solution 0.5 mg/ml.
•The effect of the once and twice daily dosing regimen of amlodipine on the mean SBP and DBP and amlodipine plasma concentrations.
•The taste of amlodipine oral solution 0.5 mg/ml using VAS.
•The preference of formulation of children and their parents using a questionnaire including ease of administration and patient acceptance. .

•De veiligheid van amlodipine orale oplossing 0.5 mg/ml.
•Het effect van éénmaal en tweemaal daags doseren van amlodipine op de SBD en DBD en amlodipine bloedspiegels.
•De smaak van amlodipine orale oplossing 0.5 mg/ml m.b.v. een visueel analoge schaal.
•De voorkeur van kinderen en hun ouders voor de toedieningsvorm van amlodipine m.b.v. een vragenlijst.

E.5.2.1

Timepoint(s) of evaluation of this end point

All secondary endpoints will be evaluated after completion of the study.

Alle secundaire eindpunten zullen geevalueerd worden nadat de studie is voltooid.

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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

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)

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)

Yes

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

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

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

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Children will be able to continue their treatment with amlodipine oral liquid 0.5 mg/ml after the study is completed

Kinderen hebben de mogelijkheid om hun behandeling met amlodipine orale oplossing 0.5 mg/ml voort te zetten nadat het onderzoek is afgelopen.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2014-05-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-07-24

P. End of Trial
P.	End of Trial Status	Ongoing

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