Clinical Trials Register

Summary
EudraCT Number:	2011-004064-29
Sponsor's Protocol Code Number:	CS747S-B-U4003
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-03-30
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

UK - MHRA

A.2

EudraCT number

2011-004064-29

A.3

Full title of the trial

A PHARMACODYNAMIC EVALUATION OF SWITCHING FROM TICAGRELOR TO PRASUGREL IN SUBJECTS WITH STABLE CORONARY ARTERY DISEASE: 2ND SWITCHING ANTIPLATELET AGENTS (SWAP 2)

A.3.1

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

A trial investigating the effects of switching from one anitiplatelet drug to another in subject with stable Coronary Artery Disease

A.3.2

Name or abbreviated title of the trial where available

SWAP 2

A.4.1

Sponsor's protocol code number

CS747S-B-U4003

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	Daiichi Sankyo, Inc.
B.1.3.4	Country	United States
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	Daiichi Sankyo, Inc.
B.4.2	Country	United States
B.4.1	Name of organisation providing support	Eli Lilly
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Daiichi Sankyo, Inc.
B.5.2	Functional name of contact point	Medical Research and Strategy
B.5.3	Address:
B.5.3.1	Street Address	2 Hilton Court
B.5.3.2	Town/ city	Parsippany
B.5.3.3	Post code	NJ 07054
B.5.3.4	Country	United States
B.5.4	Telephone number	0019739442600
B.5.5	Fax number	001 9739442645
B.5.6	E-mail	mrozek@dsi.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	Prasugrel hydrochloride
D.3.2	Product code	Prasugrel
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.3.9.1	CAS number	389574-19-0
D.3.9.2	Current sponsor code	CS-747 hydrochloride salt, LY640315
D.3.9.3	Other descriptive name	LY640315
D.3.9.4	EV Substance Code	SUB30236
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: 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	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.3.2	Product code	Ticagrelor
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	Ticagrelor
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	90
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

Stable Coronary Artery Disease

E.1.1.1

Medical condition in easily understood language

Heart Disease

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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10013098
E.1.2	Term	Disease coronary artery
E.1.2	System Organ Class	10007541 - Cardiac 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 compare the pharmacodynamic (PD) effects, expressed as P2Y12 reaction units (PRU) by the VerifyNow P2Y12 assay, in subjects with stable coronary artery disease (CAD), treated with prasugrel 10 mg daily (QD) maintenance dose (MD) (Arms A + B) and in subjects treated with ticagrelor 90 mg twice daily (BID) MD (Arm C), after 7 days of randomized study treatment.

E.2.2

Secondary objectives of the trial

To compare the PD effects measured:

*By the Vasodilator-stimulated phosphoprotein (VASP) assay (platelet reactivity index [PRI]), in all subjects treated with prasugrel 10 mg QD MD (Arms A + B) and in subjects treated with ticagrelor 90 mg BID MD (Arm C) after 7 days of randomized treatment
*Using the VerifyNow Assay device-reported and calculated percent inhibition in subjects treated on Arms A + B and in subjects treated on Arm C after 7 days of randomized treatment

To compare the PD effects, in terms of PRU, VerifyNow Assay device-reported and calculated percent inhibition, and PRI, in subjects treated on:

*Arm A (prasugrel 60 mg loading dose [LD] + 10 mg QD MD) and in subjects treated on Arm C (ticagrelor 90 mg BID MD), at all time points
*Arm B (prasugrel 10 mg QD MD) vs. Arm C (ticagrelor 90 mg BID MD), at all time points

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

As emerging information regarding the safety and efficacy of thienopyridines and cyclopentyltriazolopyrimidines may become available in the future, all subjects will have the option to allow a pharmacogenomic blood sample to be taken and retained for possible future research. This is optional. Additional blood would be drawn at visit 3.

E.3

Principal inclusion criteria

1. Male or female; age ≥ 18 and < 75 years
2. Weight ≥ 60 kg
3.Receiving low dose ASA (75 mg to 150 mg daily) for at least 7 days at the time of Visit 1 and able to continue the same regimen throughout the study
4. Stable CAD. CAD is defined as any of the following:
a. History of a positive stress test
b. Previous coronary revascularization including percutaneous coronary intervention (PCI), stent, or coronary artery bypass graft (CABG)
c. Angiographic demonstration of CAD (at least 1 lesion ≥ 50 percent)
d. Presence of at least moderate plaque by computed tomography (CT) angiography
e. Electron beam CT coronary artery calcification score > 100 Agatston units
5. If female, may be enrolled if
One of the following 3 criteria are met:
i. Had a hysterectomy or tubal ligation at least 6 months prior to signing the informed consent form (ICF)
ii. Post-menopausal for at least 1 year
iii. If of childbearing potential, will practice 1 of the following methods of birth control throughout the study: oral, injectable, or implantable hormonal contraceptives; intrauterine device; diaphragm plus spermicide; or female condom plus spermicide. Methods of contraception that are not acceptable are partner’s use of condoms or partner’s vasectomy
6. Able and willing to provide written informed consent before entering the study

E.4

Principal exclusion criteria

1. Have a defined need for adenosine diphosphate (ADP)-receptor inhibitor therapy, such as any of the following (or any other condition that in the Investigator’s judgment would require such therapy):

a. Within ≤ 12 months of an acute coronary syndrome (ACS) event (unstable angina [UA], non-ST-elevation myocardial infarction [NSTEMI], or ST-elevation myocardial infarction [STEMI]) regardless of initial treatment (that is, invasive versus noninvasive)

b. Subjects who underwent angioplasty within 12 months including bare-metal stent and/or a drug-eluting stent
c. Had any stent placed in an unprotected left main coronary artery or in the last patent artery within the last 12 months

2. Received thienopyridine therapy within 30 days of study entry

3. Plan to undergo coronary revascularization at any time during the trial

4. Presence or history of any of the following: ischemic or hemorrhagic stroke; transient ischemic attack (TIA); intracranial neoplasm; arteriovenous malformation, or aneurysm; intracranial hemorrhage; head trauma (within 3 months of study entry)

5. History of refractory ventricular arrhythmias with an increased risk of bradycardic events (eg, subjects without a pacemaker who have sick sinus syndrome, 2nd or 3rd degree atrioventricular (AV) block or bradycardic-related syncope)

6. History or evidence of congestive heart failure (New York Heart Association Class III or above)

7. Severe hepatic impairment

8. History of uric acid nephropathy

9. Uncontrolled hypertension, or systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg at screening

10. Severely impaired renal function (glomerular filtration rate < 30 mL/minute) or on dialysis

11. At risk for bleeding

12.Taking prohibited medications

13.Meets any of the general exclusion criteria

E.5 End points

E.5.1

Primary end point(s)

PRU by VerifyNow P2Y12 assay for prasugrel 10 mg QD MD (Arm A + B) and ticagrelor 90 mg BID MD (Arm C) after 7 days of randomized treatment.

E.5.1.1

Timepoint(s) of evaluation of this end point

After 7 days of randomized treatment.

E.5.2

Secondary end point(s)

• PRI by the VASP assay 2, 4, 24, 48 hours, and 7 days after first randomized study treatment
• PRU by the VerifyNow P2Y12 assay 2, 4, 24, and 48 hours after first randomized study treatment
• VerifyNow assay device-reported and calculated percent inhibition 2, 4, 24, and 48 hours, and 7 days after first randomized study treatment
• Percentage of subjects with HPR, defined as a) ≥ 208 PRU and b) ≥ 230 PRU by the VerifyNow P2Y12 assay, and c) >50% PRI by the VASP assay, 2, 4, 24, and 48 hours and 7 days after first randomized study treatment

E.5.2.1

Timepoint(s) of evaluation of this end point

See above section E.5.2

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

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

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

Yes

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)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Different dosage of the same product

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

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

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

last subject last visit

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

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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

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

105

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

2012-03-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-06-11

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-02-13

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