Clinical Trials Register

Summary
EudraCT Number:	2012-002896-32
Sponsor's Protocol Code Number:	D5136C00001
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:
Date on which this record was first entered in the EudraCT database:	2013-06-19
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

France - ANSM

A.2

EudraCT number

2012-002896-32

A.3

Full title of the trial

A multicenter, double-blind, placebo-controlled, pharmacokinetic, pharmacodynamic, safety and tolerability study in patients aged 12 to <18 years of age with a central venous catheter to support prediction of the age appropriate dose of ticagrelor with similar levels of inhibition of platelet aggregation to 90 mg bd in adults

Une étude multicentrique, pharmacocinétique, pharmacodynamique, d’innocuité et de tolérabilité, menée en double aveugle et contrôlée par placebo sur des patients âgés de 12 à <18 ans portant un cathéter veineux central pour aider au calcul de la dose de ticagrelor correspondant à l’âge du patient, avec des niveaux similaires d’inhibition de l’agrégation plaquettaire, de l’ordre de 90 mg bd chez les adultes

A.3.1

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

A study to determine how much ticagrelor needs to be given to children and adolescents with a central venous catheter.

Une étude pour déterminer la dose de ticagrelor à administrer à des enfants et des adolescents portant un cathéter veineux central

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

D5136C00001

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/255/2012

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	AstraZeneca AB
B.4.2	Country	Sweden
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	ticagrelor 45 mg, tablets
D.3.2	Product code	AZD6140
D.3.4	Pharmaceutical form	Film-coated tablet
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.3.8	INN - Proposed INN	Ticagrelor
D.3.9.1	CAS number	274693-5
D.3.9.2	Current sponsor code	AZD6140
D.3.9.3	Other descriptive name	TICAGRELOR
D.3.9.4	EV Substance Code	SUB30898
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	45
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Thrombosis, thromboembolism

E.1.1.1

Medical condition in easily understood language

Blod clot

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.0
E.1.2	Level	PT
E.1.2	Classification code	10050661
E.1.2	Term	Platelet aggregation inhibition
E.1.2	System Organ Class	10005329 - Blood and lymphatic system disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the pharmacodynamics of ticagrelor (45 mg bd), measured as the final extent of inhibition of platelet aggregation in paediatric patients aged from 12 to <18 years of age.

E.2.2

Secondary objectives of the trial

To examine the pharmacokinetic profile of ticagrelor in paediatric patients 12 to <18 years of age.
To evaluate the relationship between ticagrelor exposure and platelet aggregation inhibition.
To assess the safety and tolerability of ticagrelor in patients aged 12 to <18 years of age with a central venous catheter by evaluation of adverse events, including bleeding events.
To evaluate the relationship between inhibition of platelet aggregation and platelet reactivity index by determining the platelet reactivity index.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Written informed consent for study participation must be obtained prior to any study related procedures being performed and according to international guidelines and/or applicable EU guidelines
Patients aged 12 to <18 years with a central venous catheter (CVC) with intended use for at least 5 days at
time of randomisation.
All post-menarche females are required to have a negative pregnancy test. Male and female patients are to adhere to appropriate contraceptive measures (if appropriate to the age of the child).

E.4

Principal exclusion criteria

Sign or suspicion of extra-vascular bleeding in connection with placement of the CVC (>24 hours need to have elapsed since any sign or suspicion of ongoing bleeding, in order to allow randomisation of the patient).
Patients who have an ongoing bleeding, risk of bleeding, previous intracranial haemorrhage, or platelet count <100,000 x 109/L.
Surgery within 7 days unless judged to be a low risk for bleeding and at least 24 hours after surgery.
Patients who are taking aspirin or other non-steroidal anti-inflammatory drugs within a week before randomisation and during the study period.
Patients who are taking ADP receptor blockers (eg, clopidogrel, prasugrel,ticlopidine), dipyridamole, and cilostazol within a week before randomisation and during the study period.

E.5 End points

E.5.1

Primary end point(s)

Pharmacodynamics of ticagrelor:Final extent of inhibition of platelet aggregation(IPA). IPA will be assessed via light transmission aggregometry of platelet rich plasma with 3.2% sodium citrate as the anticoagulant and 20 umol/L of ADP as the agonist.

E.5.1.1

Timepoint(s) of evaluation of this end point

On days 1 and 5 as well as after 2 day's follow-up

E.5.2

Secondary end point(s)

#1) To examine the pharmacokinetic profile of ticagrelor by assessment of maximum concentration, time to maximum concentration, area under the plasma time concentration curve and accumulation ratio

#2) To evaluate the relationship between ticagrelor exposure and platelet aggregation inhibition (IPA)

#3) To assess the safety and tolerability ticagrelor by assessment of adverse events (AEs) including bleeding, laboratory values, physical examination, vital signs and ECG

#4) To evaluate the relationship between inhibition of platelet aggregation (IPA) and platelet reactivity index (PRI). PRI will be determined by measurement of vasodilator-stimulated phosphoprotein phosphorylation (VASP-P)

E.5.2.1

Timepoint(s) of evaluation of this end point

#1) On days 1 and 5

#2) On days 1 and 5

#3) AEs during the study, lab and vital signs at baseline, day 5 and 2 day's follow-up, phys exam at baseline and 2 days' follow-up, ECG at baseline, days 1 and 5, 2 day's follow-up

#4) On days 1 and 5 as well as after 2 day's follow-up

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

Yes

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

LSLV

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial 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)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

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

Yes

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

Paediatric population aged 12 to less than 18 years of age with a condition requiring central venous catheter.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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)

Standard of care

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

2013-01-25

Ethics Committee Opinion of the trial application

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

P. End of Trial
P.	End of Trial Status

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