Clinical Trials Register

Summary
EudraCT Number:	2012-002563-10
Sponsor's Protocol Code Number:	BAY86-4875/15961
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-03-27
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2012-002563-10

A.3

Full title of the trial

Multicenter open-label study to evaluate efficacy of gadobutrol-enhanced cardiac magnetic resonance imaging (CMRI) for detection of significant coronary artery disease (CAD) in subjects with known or suspected CAD by a blinded image analysis

A.3.1

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

Gadobutrol/Gadavist-enhanced cardiac magnetic resonance imaging (CMRI) to detect Coronary Artery Disease (CAD)

A.3.2

Name or abbreviated title of the trial where available

GadaCAD 1

A.4.1

Sponsor's protocol code number

BAY86-4875/15961

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	Bayer HealthCare AG
B.1.3.4	Country	Germany
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	Bayer HealthCare AG
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Bayer HealthCare AG
B.5.2	Functional name of contact point	Bayer Clinical Trials Contact
B.5.3	Address:
B.5.3.1	Street Address	CTP Team/Ref: "EU CTR" / Bayer Pharma AG
B.5.3.2	Town/ city	Berlin
B.5.3.3	Post code	D-13342
B.5.3.4	Country	Germany
B.5.6	E-mail	clinical-trials-contact@bayerhealthcare.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	Gadovist® 1.0mmol/ml, solution for injection
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer Vital GmbH
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	Gadovist® 1.0 mmol/ml, solution for injection
D.3.2	Product code	BAY 86-4875
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Gadobutrol
D.3.9.1	CAS number	138071-82-6
D.3.9.2	Current sponsor code	BAY 86-4875
D.3.9.3	Other descriptive name	GADOBUTROL
D.3.9.4	EV Substance Code	SUB07861MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mmol/ml millimole(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1.0
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.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Regadenoson
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Regadenoson
D.3.9.1	CAS number	313348-27-5
D.3.9.3	Other descriptive name	REGADENOSON
D.3.9.4	EV Substance Code	SUB30494
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	400
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	Yes
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Adenosine
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Adenosine
D.3.9.1	CAS number	58-61-7
D.3.9.3	Other descriptive name	ADENOSINE
D.3.9.4	EV Substance Code	SUB00297MIG
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	3
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

Subjects with known or suspected Coronary Artery Disease (CAD)

E.1.1.1

Medical condition in easily understood language

Known or suspected disease of the coronary arteries

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01]

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 efficacy objectives of this study are to demonstrate that sensitivity and specificity of gadobutrol-enhanced CMRI exceed pre-specified minimum performance thresholds (MPT) of 60 and 55%, respectively and to show superior sensitivity over unenhanced wall motion CMRI at vasodilator rest/stress for the detection of significant CAD:
Primary objectives (i.e. 3 co-primaries) are to
1) demonstrate that subject-based sensitivity of gadobutrol-enhanced CMRI at vasodilator stress/rest (lower bound of 95% CI) exceeds the predefined minimum performance threshold of 60%;
2) demonstrate that subject-based specificity of gadobutrol-enhanced CMRI at vasodilator stress/rest (lower bound of 95% CI) exceeds the predefined minimum performance threshold of 55%;
3) demonstrate subject-based superior sensitivity of gadobutrol-enhanced CMRI over unenhanced wall motion CMRI.

E.2.2

Secondary objectives of the trial

1) demonstrate that subject-based sensitivity and specificity, of gadobutrol-enhanced CMRI (lower bound of 95% CI) exceed 60% and 55%, respectively.
2) demonstrate subject-based superior sensitivity of gadobutrol-enhanced CMRI compared to unenhanced wall motion CMRI.
3) evaluate coronary territory-based sensitivity and specificity of gadobutrol-enhanced CMRI for localization of CAD;
• for territories LAD and non-LAD;
• additional localization for RCA and LCX;
4) evaluate detection and perfusion pattern of subjects with LMS stenosis;
5) evaluate subject-based sensitivity and specificity of gadobutrol- enhanced CMRI for detection and exclusion of significant CAD separately in 2 subgroups:
-subjects with single-vessel disease and
-subjects with multi-(2- or 3)-vessel disease.
6) assess the confidence of diagnosis for each defined myocardial region for unenhanced wall motion and gadobutrol-enhanced CMRI.
7) confirm the safety profile of gadobutrol in this indication.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Male or female subjects aged ≥18 years
- Subjects with suspected or known CAD based on signs and/or (typical or atypical) chest pain who have routine CA without intervention or CTA within 4 weeks around gadobutrol-enhanced CMRI
- Willingness to undergo stress/rest CMRI and to follow directions and complete all study procedures
- Women of childbearing potential (e.g. age < 60y, no history of surgical sterilization or hysterectomy): use of contraception and a negative pregnancy test

E.4

Principal exclusion criteria

- Suspected clinical instability or unpredictability of the clinical course during the study period
- Contraindication to the cardiac MRI examination (e.g. inability to hold breath; severe claustrophobia, metallic devices such as pace makers)
- History of severe allergic or anaphylactoid reaction to any allergen including drugs and contrast agents according to the investigator’s assessment / judgment
- Estimated glomerular filtration rate (eGFR) value <30 mL/min/1.73 m2 derived from a serum / blood creatinine result within 2 weeks prior to gadobutrol injection. Any subject on hemodialysis or peritoneal dialysis is excluded from enrollment.
- Acute renal insufficiency
- Coronary artery bypass grafting (CABG)
- Acute myocardial infarction (< 14 days prior to inclusion), unstable angina / acute coronary syndrome, severe congestive heart failure
- Irregular heart rhythm
- Condition that precludes the safe administration of pharmacological stressor according to the respective approved label such as sinus node disease, 2nd or 3rd degree atrioventricular block, obstructive lung disease

E.5 End points

E.5.1

Primary end point(s)

1. Presence of a myocardial perfusion defect indicating significant CAD [coronary artery disease] per subject on gadobutrol-enhanced CMRI [cardiac magnetic resonance imaging] (based on regional perfusion score), based on the blinded readers’ assessment.
2. Absence of a myocardial perfusion defect excluding significant CAD per subject on gadobutrol-enhanced CMRI (based on regional perfusion score), based on the blinded readers’ assessment.
3. Presence of a myocardial perfusion defect indicating significant CAD per subject on gadobutrol-enhanced CMRI versus unenhanced wall motion CMRI images (based on regional perfusion/regional wall motion score), based on the blinded readers’ assessment.

E.5.1.1

Timepoint(s) of evaluation of this end point

Up to 8 weeks

E.5.2

Secondary end point(s)

1. Presence of a myocardial perfusion defect indicating significant CAD per subject on gadobutrol-enhanced CMRI (investigator's assessment).
2. Absence of myocardial perfusion defect excluding significant CAD per subject on gadobutrol-enhanced CMRI (investigator's assessment).
3. Presence of a myocardial perfusion defect indicating significant CAD per subject on gadobutrol-enhanced CMRI versus unenhanced wall motion CMR images (investigator's assessment).
4. Localization of a myocardial perfusion defect to a coronary territory, i.e. LAD [left anterior descending artery] and non-LAD, on gadobutrol-enhanced CMRI (blinded readers' and investigator's assessments).
5. Additional localization of a non-LAD myocardial perfusion defect to RCA [right coronary artery] and LCX [left circumflex artery] territory respectively on gadobutrol-enhanced CMRI (blinded readers' and investigator's assessments).
6. Detection of subjects with LMS [left main stem] stenosis.
7. Perfusion pattern of subjects with LMS stenosis.
8. Presence/absence of a myocardial perfusion defect indicating/excluding significant CAD (per subject), in subjects with multi-vessel versus single vessel disease evaluated on gadobutrol-enhanced CMRI (blinded readers' and investigator's assessments).
9. Score for confidence of diagnosis for each myocardial region on unenhanced wall motion and gadobutrol-enhanced CMR images (blinded readers' and investigator's assessments).

E.5.2.1

Timepoint(s) of evaluation of this end point

Up to 8 weeks

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

E.6.2

Prophylaxis

E.6.3

Therapy

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

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

Yes

E.8.2.3.1

Comparator description

Unenhanced CMRI

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

France

Germany

Korea, Republic of

New Zealand

Switzerland

United Kingdom

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

For each participating EU country, the end of the study according to the EU Clinical trial Directive) will be reached when the last visit of the last subject for all centers in the respective country has occurred. As for this study, the primary outcome will be collected after last patient (or subject) last visit (LPLV), the end of the study as a whole will be the date when the clean database is available.

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:

135

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

315

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

183

F.4.2

For a multinational trial

F.4.2.1

In the EEA

275

F.4.2.2

In the whole clinical trial

450

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)

Not applicable for this diagnostic study

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

2013-06-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-05-14

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-08-31

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials