Clinical Trials Register

Summary
EudraCT Number:	2016-004232-37
Sponsor's Protocol Code Number:	D5134C00003
National Competent Authority:	Slovakia - SIDC (Slovak)
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2018-02-27
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
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

Slovakia - SIDC (Slovak)

A.2

EudraCT number

2016-004232-37

A.3

Full title of the trial

A Randomised, Double-Blind, Placebo-Controlled, International, Multicentre, Phase III Study to Investigate the Efficacy and Safety of Ticagrelor and ASA Compared with ASA in the Prevention of Stroke and Death in Patients with Acute Ischaemic Stroke or Transient Ischaemic Attack

Randomizované, dvojito-zaslepené, placebom kontrolované medzinárodné,
multicentrické klinické skúšanie vo fáze III, ktorého cieľom je porovnať
preventívny účinok kombinovanej liečby tikagreloru a aspirínu(ASA) oproti
monoterapii ASA na výskyt cievnej mozgovej príhody a smrti u pacientov s
akútnou ischemickou cievnou mozgovou príhodou alebo TIA

A.3.1

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

Study to investigate if the study drug ticagrelor and ASA is more effective than Placebo (inactive tablet) and ASA in preventing new stroke events.

Klinické skúšanie, ktorého cieľom je porovnať preventívny účinok liečby
tikagreloru a aspirínu(ASA) oproti monoterapii ASA na výskyt cievnej
mozgovej príhody a smrti u pacientov s akútnou ischemickou cievnou
mozgovou príhodou alebo TIA

A.3.2

Name or abbreviated title of the trial where available

THALES

A.4.1

Sponsor's protocol code number

D5134C00003

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	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 AB
B.5.2	Functional name of contact point	Information Center
B.5.3	Address:
B.5.3.1	Street Address	Karlebyhus, Astraallén
B.5.3.2	Town/ city	Södertälje
B.5.3.3	Post code	SE 151 85
B.5.3.4	Country	Sweden
B.5.4	Telephone number	1877-240-9479
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	Yes
D.2.1.1.1	Trade name	Brilique
D.2.1.1.2	Name of the Marketing Authorisation holder	AstraZeneca AB
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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.3.4	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	274693-27-5
D.3.9.2	Current sponsor code	AZD6140, AR-C126532XX
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	180
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	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

Ischaemic stroke, transient ischaemic attack

E.1.1.1

Medical condition in easily understood language

Stroke, transient ischaemic attack

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	21.1
E.1.2	Level	PT
E.1.2	Classification code	10061256
E.1.2	Term	Ischaemic stroke
E.1.2	System Organ Class	10029205 - Nervous system disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To demonstrate superior efficacy of ticagrelor and ASA compared with placebo and ASA in patients with acute ischaemic stroke (AIS) or TIA in the prevention of the composite of stroke and death at 30 days

E.2.2

Secondary objectives of the trial

1. To demonstrate superior efficacy of ticagrelor and ASA compared with placebo and ASA in AIS/TIA patients in the prevention of ischaemic stroke at 30 days
2. To demonstrate superior efficacy of ticagrelor and ASA compared with placebo and ASA in AIS/TIA patients in reducing overall disability at 30 days

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Provision of signed informed consent prior to any study-specific procedure
3.≥40 years of age
3.Acute onset of cerebral ischaemia due to
(a) AIS with NIHSS ≤5. AIS is defined as acute onset of neurological deficit attributed to focal brain ischaemia, and either of the following:
-Persistent signs or symptoms of the ischaemic event at the time of
randomisation, OR
-Acute ischaemic brain lesion documented before randomisation by computed tomography (CT) scan or magnetic resonance imaging (MRI) (diffusion-weighted imaging) and that could account for the clinical presentation
(b) High-risk TIA, defined as neurological deficit of acute onset attributed to focal ischaemia of the brain by history or examination with complete resolution of the deficit, and at least one of the following:
-ABCD2 score ≥6 and TIA symptoms not limited to isolated numbness, isolated visual changes, or isolated dizziness/vertigo
-Symptomatic intracranial arterial occlusive disease that could account for the clinical presentation, documented by transcranial Doppler or vascular imaging and defined as at least 50% narrowing in the diameter of the vessel lumen
-Internal carotid arterial occlusive disease that could account for the clinical presentation, documented by Doppler, ultrasound, or vascular imaging and defined as at least 50% narrowing in diameter of the vessel lumen
4. Randomisation occurring within 24 hours after onset of symptoms; for wake-up strokes (when the time of symptom onset is not known), within 24 hours from the time point at which the patient was reported to be in their normal condition
5. CT or MRI performed after symptom onset ruling out intracranial haemorrhage or
other pathology, such as vascular malformation, tumour, or abscess that according
to the Investigator could explain symptoms or contraindicate study treatment

E.4

Principal exclusion criteria

1.Need for or an anticipated need for any of the following:
(a) Dual antiplatelet therapy with ASA and P2Y12 inhibitors (including patients with carotid artery stenting and percutaneous coronary intervention)
(b) Antiplatelets other than ASA (eg, GPIIb/IIIa inhibitors, clopidogrel, ticlopidine, prasugrel, dipyridamole, ozagrel, cilostazol, ticagrelor) and other antithrombotic agents with antiplatelet effects, including traditional/herbal medicine agents
(c) Anticoagulants (eg, warfarin, oral thrombin and factor Xa inhibitors, bivalirudin, hirudin, argatroban, fondaparinux, or unfractionated heparin and long-term treatment with low-molecular weight heparins). Short-term treatment (≤7 days) with low-dose low-molecular weight heparin may be used in immobilised patients at the discretion of the Investigator
2.Any history of atrial fibrillation/flutter, ventricular aneurysm, or suspicion of other cardioembolic pathology for TIA or stroke
3.Patients who should receive or have received any intravenous or intra-arterial thrombolysis or mechanical thrombectomy within 24 hours prior to randomisation
4.Planned carotid endarterectomy that requires halting investigational product within 3 days of randomisation or is expected to require unblinding of investigational product (planned carotid endarterectomy is in itself not an exclusion criterion)
5.History of previous intracranial haemorrhage at any time (asymptomatic microbleeds do not qualify), gastrointestinal haemorrhage within the past 6 months, or major surgery within 30 days
6.Patients considered to be at risk of bradycardic events (eg, known sick sinus syndrome or second- or third-degree atrioventricular block) unless already treated with a permanent pacemaker
7.Inability of the patient to understand and/or comply with study procedures and/or follow-up, in the opinion of the Investigator
8.Known hypersensitivity to ticagrelor or ASA
9.Need for or an anticipated need for oral or intravenous therapy with any of the following:
(a) Strong cytochrome P450 3A (CYP3A4) inhibitors (eg, ketoconazole, clarithromycin [but not erythromycin or azithromycin], nefazadone, ritonavir, atazanavir) that cannot be stopped for the course of the study
(b) Long-term (>7 days) non-steroidal anti-inflammatory drugs
10.Known bleeding diathesis or coagulation disorder (eg, thrombotic thrombocytopenic purpura)
11.Known severe liver disease (eg, ascites or signs of coagulopathy)
12.Renal failure requiring dialysis
13.Pregnancy or breastfeeding. Women of child-bearing potential who are not willing to use a medically accepted method of contraception that is considered reliable in the judgment of the Investigator
14.Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
15.Previous enrolment or randomisation in the present study
16.Participation in another clinical study with an investigational product at any time during the 30 days prior to randomisation (regardless of when treatment with the investigational product was discontinued)

E.5 End points

E.5.1

Primary end point(s)

Time from randomisation to first subsequent stroke or death

E.5.1.1

Timepoint(s) of evaluation of this end point

From randomization up to 30 days

E.5.2

Secondary end point(s)

1. Time from randomisation to first subsequent ischaemic stroke
2. mRS score >1 at Visit 3

E.5.2.1

Timepoint(s) of evaluation of this end point

1. From randomization up to 30 days.
2. Day 30.

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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

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)

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)

Yes

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

191

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Argentina

Australia

Belgium

Brazil

Bulgaria

Canada

China

Czech Republic

France

Germany

Hong Kong

Hungary

India

Italy

Korea, Republic of

Mexico

Peru

Poland

Romania

Russian Federation

Saudi Arabia

Slovakia

Spain

Sweden

Taiwan

Thailand

Ukraine

Vietnam

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

The end of the trial is defined as the last visit of the last subject undergoing the trial.

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 months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

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)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

5500

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

5500

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

Yes

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

600

F.4.2

For a multinational trial

F.4.2.1

In the EEA

4500

F.4.2.2

In the whole clinical trial

11000

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)

None

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

2017-12-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-02-08

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-12-13

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