Clinical Trials Register

Summary
EudraCT Number:	2012-001584-77
Sponsor's Protocol Code Number:	MEIN/10/Ran-PCI/005
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2012-07-18
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

Germany - BfArM

A.2

EudraCT number

2012-001584-77

A.3

Full title of the trial

Effect of Ranolazine in ischemic patients with indication of staged interventional therapy

Effekt von Ranolazin bei Patienten mit Ischämie mit der Indikation einer interventionellen Therapie

A.3.1

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

A study to investigate the effect of a drug to treat Angina pectoris

A.3.2

Name or abbreviated title of the trial where available

ERASER

A.4.1

Sponsor's protocol code number

MEIN/10/Ran-PCI/005

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	Menarini International Operations Luxembourg S.A.
B.1.3.4	Country	Luxembourg
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	A. Menarini Manufacturing Logistics & Services
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Dr. Notghi Contract Research GmbH
B.5.2	Functional name of contact point	Project Manager
B.5.3	Address:
B.5.3.1	Street Address	Zimmerstraße 55
B.5.3.2	Town/ city	Berlin
B.5.3.3	Post code	10117
B.5.3.4	Country	Germany
B.5.4	Telephone number	004903046064780
B.5.5	Fax number	004903046064733
B.5.6	E-mail	eraser@notghi.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	Ranexa® 500 mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Menarini international Operations Luxembourg S.A.
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.3.1	Product name	Ranexa
D.3.4	Pharmaceutical form	Prolonged-release 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	RANOLAZINE
D.3.9.1	CAS number	95635-55-5
D.3.9.4	EV Substance Code	SUB10259MIG
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	500
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	Ranexa® 750 mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Menarini International Operations Luxembourg S.A.
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.3.1	Product name	Ranexa
D.3.4	Pharmaceutical form	Prolonged-release 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	RANOLAZINE
D.3.9.1	CAS number	95635-55-5
D.3.9.4	EV Substance Code	SUB10259MIG
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	750
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
D.8 Placebo: 2
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

Stable Angina Pectoris

E.1.1.1

Medical condition in easily understood language

Chest tightness

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	15.0
E.1.2	Level	LLT
E.1.2	Classification code	10049194
E.1.2	Term	Stable angina pectoris
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

Primary objective of this study is to evaluate the efficacy of ranolazine treatment in terms of changes of wall motion abnormalities in ischemic areas in patients treated with ranolazine compared to patients treated with placebo at follow-up magnetic resonance examination after five weeks of ranolazine treatment.

E.2.2

Secondary objectives of the trial

Secondary Objectives:

Evaluation of the heart’s perfusion deficit, dynamic geometry and related variables:
• transmural extent of perfusion deficit
• hyperenhancement
• new hyperenhancement
• left ventricular ejection fraction (LVEF, %)
• left ventricular end-diastolic volume index (LVEDVI, mL/m2)
• left ventricular end-systolic volume index (LVESVI, mL/m2)
• stroke volume index (SVI, mL/m2)
• left ventricular mass index (LVMI, g/m2)
• left ventricular mass absolute (LV mass, g)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Subjects must meet all of the following inclusion criteria to be eligible for participation in this study.

1. Male and female patients (females of childbearing potential must have a negative urine pregnancy test and must be using adequate contraceptive precautions, see also section 17.4)

2. Performed coronary angiography with or without initial PCI more than 24 hours before MRI

3. Remaining ≥ 70% stenosis of a coronary artery bigger than 2 mm diameter (not corrected by PCI)

4. Indication of further interventional treatment

5. Wall motion abnormalities in at least one segment; if segment 17 is affected, an additional segment has to show wall motion abnormalities (for the segment-model, see section 13.3.3)

6. History of chronic angina pectoris

7. Age ≥ 18 years

8. Normalized blood pressure < 140/90 mmHg and heart rate < 70 bpm and ≥ 50 bpm at rest

9. Sinus rhythm

10. Standard therapy: beta-blocker and/or calcium channel blocker (stable for 4 weeks)

11. Signed informed consent

E.4

Principal exclusion criteria

Subjects who meet any of the following exclusion criteria are not enrolled in this study:

1. Cardiac instability, e.g. acute coronary syndrome as indication for the coronary angiography (ST-elevation or positive troponin testing)

2. Contraindication for MRI (e.g. implanted pace maker, internal defibrillator, MRI incompatible devices or metals)

3. Contraindication for dobutamine, atropine, gadolinium based contrast agent, or metoprolol

4. Patients with heart failure classification NYHA III and NYHA IV

5. Myocardial infarction during the last 3 days prior to treatment with ranolazine

6. Severe renal impairment (GFR < 30 ml/min)

7. Moderate or severe hepatic impairment (ALT or AST > 2.5× upper normal limit)

8. Allergic asthma bronchiale

9. Hyperthyroidism or Hashimoto thyreoiditis

10. Myocarditis or inflammatory heart disease

11. Hypertrophic obstructive cardiomyopathy

12. Concomitant administration of class Ia (e.g. quinidine) or class III (e.g. dofetilide, sotalol) antiarrhythmics, except for amiodarone

13. Long acting nitrates

14. Concomitant treatment with potent inhibitors of CYP3A (see also section 11.4)

15. Concomitant treatment with CYP3A inducers (see also section 11.4)

16. Dronedarone

17. Use of greater than 1000 mg daily dose of metformin during the study

18. Hypersensitivity to the active substance or to any of the excipients

19. Hypersensitivity to dobutamine, atropine, gadolinium based contrast agent, or metoprolol

20. Concomitant administration of > 20 mg simvastatin/day

21. History of ECG abnormalities that, in the opinion of the investigator, render the patient unsuitable for the trial, e.g. history of long QT syndrome or significant prolonged QT interval (> 120%)

22. Participation in another trial of an investigational drug or device within 30 days prior to screening

23. Pregnant and breast-feeding women (females of childbearing potential or within two years from the menopause must have a negative urine pregnancy test)

24. Less than 3 months since delivery, abortion, or lactation before the first screening/examination visit

25. Severe psychiatric disorders/neurological disorders

26. Suspected abuse of alcohol, analgesics or psychotropic drugs

27. Disabling or terminal illness

28. Inability or unwillingness to issue the informed consent

E.5 End points

E.5.1

Primary end point(s)

Primary end point:

The changes of the wall motion abnormalities will be compared between the two treatment groups (ranolazine versus placebo)

E.5.1.1

Timepoint(s) of evaluation of this end point

After 5 week, day 35 +/- 3 of study drug administration

E.5.2

Secondary end point(s)

The secondary endpoints are:

to compare the effects of ranolazine versus placebo on the evaluation of the heart’s perfusion deficit, dynamic geometry and related variables:

• transmural extent of perfusion deficit
• hyperenhancement
• new hyperenhancement
• left ventricular ejection fraction (LVEF)
• left ventricular end-diastolic volume index (LVEDVI)
• left ventricular end-systolic volume index (LVESVI)
• stroke volume index (SVI)
• left ventricular mass index
• left ventricular mass absolute.

E.5.2.1

Timepoint(s) of evaluation of this end point

After 5 week, day 35 +/- 3 of study drug administration

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

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)

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

Yes

E.8.4

The trial involves multiple sites in the 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

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2012-07-18.

Yes

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.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

2012-10-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-08-27

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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