Clinical Trials Register

Summary
EudraCT Number:	2011-001278-24
Sponsor's Protocol Code Number:	MEIN/10/Ran-Cad/003
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2011-08-18
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Austria - BASG

A.2

EudraCT number

2011-001278-24

A.3

Full title of the trial

EFFICACY OF RANOLAZINE IN PATIENTS WITH CORONARY ARTERY DISEASE (CAD)

A.3.1

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

EFFICACY OF RANOLAZINE IN PATIENTS WITH CORONARY ARTERY DISEASE (CAD)

A.4.1

Sponsor's protocol code number

MEIN/10/Ran-Cad/003

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 SA
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	Menarini International Operations Luxembourg SA
B.4.2	Country	Luxembourg
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Menarini International Operations Luxembourg SA
B.5.2	Functional name of contact point	Study Medical Expert (SME)
B.5.3	Address:
B.5.3.1	Street Address	Via Walter Tobagi, 8
B.5.3.2	Town/ city	Peschiera Borromeo
B.5.3.3	Post code	20068
B.5.3.4	Country	Italy
B.5.4	Telephone number	003902516555236
B.5.5	Fax number	00390251650530
B.5.6	E-mail	dzava@lusofarmaco.it

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
D.2.1.1.2	Name of the Marketing Authorisation holder	Menarini International Operations Luxembourg S.A.
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	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.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	NA
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.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
D.2.1.1.2	Name of the Marketing Authorisation holder	Menarini International Operations Luxembourg SA
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	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.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	NA
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	375
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.2.1.1.1	Trade name	Ranexa
D.2.1.1.2	Name of the Marketing Authorisation holder	Menarini International Operations Luxembourg SA
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	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.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	NA
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.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

Excercise angina in patients with Coronary Artery Disease

E.1.1.1

Medical condition in easily understood language

ECG alteration during exercise test in patients suffering from Coronary Artery Disease, which is a condition due to a constriction of the vessels which conduct the blood to the cardiac muscle

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	17.1
E.1.2	Level	LLT
E.1.2	Classification code	10015648
E.1.2	Term	Exercise induced angina
E.1.2	System Organ Class	100000004849

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 study objective will be to verify whether ranolazine 750 mg b.i.d. is effective in increasing exercise capacity (exercise treadmill time at peak).

E.2.2

Secondary objectives of the trial

The secondary study objectives will be to verify whether ranolazine is effective in reducing angina frequency and nitroglycerin and/or nitrates consumption/week.
The assessment of safety by evaluation of adverse events, laboratory findings and physical examination will also be considered a secondary study objective.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Male and female patients (females of childbearing potential must be using adequate contraceptive precautions such as implants, injectables, combined oral contraceptives, intrauterine devices, sexual abstinence or vasectomised partner).
• Patients aged ≥ 18 years.
• Patients with coronary artery disease confirmed by angiography or prior MI or prior revascularization (PCI, CABG) and with exercise angina not controlled by the current therapy, with or without anginal pain.
• ST-segment depression ≥ 1mm during exercise ECG.
• Capacity to perform the exercise test.
• Able and willing to sign informed consent and to comply with study procedures.
• Written informed consent prior to enrolment into the study.
• Females of childbearing potential or within two years from the menopause must have a negative urine pregnancy test

Inclusion criterion at visit 1
• Reproducible ST-segment depression ≥ 1mm during two exercise tests performed 1 week apart (difference in exercise no more than 20%).

E.4

Principal exclusion criteria

• Angina at rest
• ECG abnormalities at rest (left bundle-branch block, right bundle-branch block, resting STsegment depression ≥ 1mm, tachyarrhythmia).
• Presence of factors that preclude satisfactory interpretation of the ECG (e.g. resting ST-segment depression ≥ 1mm in any lead, left bundlebranch block, digoxin therapy) or repolarisation and conduction abnormalities.
• Heart failure (class III or IV NYHA).
• Moderate-severe hypertension (SBP>160 mmHg and/or DBP>100 mmHg).
• Hypotension.
• Acute coronary syndrome or coronary revascularization procedure within the prior 3 months before enrolment.
• Already planned revascularization (PTCA or CABG )
• Implant of a pacemaker
• Females who are pregnant or nursing.
• Any clinically relevant haematological or biochemical abnormality on routine screening, according to Investigator's judgment.
• Severe concurrent pathology, including terminal illness (cancer,
AIDS, etc.).
• Renal impairment defined as creatinine clearance< 30 mL/min.
• Mild, moderate or severe hepatic impairment or hepatic insufficiency defined as: SGOT or SGPT > 3 times greater than normal upper limit or total serum bilirubin > 1.5 times greater than normal upper limit
• Use of greater than 1000 mg daily dose of metformin during the
study.
• Use of greater than 20 mg daily dose of simvastatin during the study.
• Pre-existing QT prolongation (including congenital long QT syndrome, uncorrected hypokalemia).
• Use of following concomitant medications: potent CYP3A4 inhibitors (e.g. ketoconazole and other azole antifunginals, macrolide antibiotics, HIV protease inhibitors and grapefruit juice or grapefruit-containing product); CYP3A4 inducers (e.g. rifampicin, phenytoin, phenobarbital, carbamazepine, hypericum (St. John's wort); P-glycoprotein inhibitor (e.g. ritonavir, quinidine, ciclosporin); QT-prolonging drugs such as Class
Ia (e.g quinidine) and class III (e.g. dofetilide, sotalol, dronedarone) antiarrhytmics (aside from amiodarone), and antipsychotics (e.g., thioridazine, ziprasidone); CYP2D6 inhibitor (e.g paroxetine); other products for which interactions with the products under study have been recorded.
• Existing contraindications for exercise testing (e.g. acute myocarditis or pericarditis, DVT, severe aortic stenosis)
• Dementia, psychosis, alcoholism (>350 g ethanol/week) or chronic abuse of medicines, drugs or psychoactive substances.
Only for Germany:
• Dementia, psychosis, alcoholism (for women >140 g ethanol/week;
for men >210 g ethanol/week according to the German Office for
Questions Regarding Addiction) or chronic abuse of medicines, drugs or psychoactive substances.
• Conditions which in the Investigator's opinion may interfere with the study's execution or due to which the patient should not participate for safety reasons.
• Participation to other clinical trials in the previous three months.
• Prescription and use of off-label medications
• Risk of low patient cooperation.
• Inability or unwillingness to issue the informed consent.

E.5 End points

E.5.1

Primary end point(s)

Change in treadmill total exercise duration with ranolazine or placebo at peak ranolazine plasma levels (4 hrs after dosing)

E.5.1.1

Timepoint(s) of evaluation of this end point

After 24 weeks of full-dose treatment.

E.5.2

Secondary end point(s)

To assess the changes in the following Parameters of the treadmill
exercise test with ranolazine or Placebo at Peak ranolazine Plasma
Levels (4 hours after dosing) after 4 (Visit 6) and 12 (Visit 7) weeks of
full-dose Treatment:
- Change in treadmill total exercise Duration
- Change in time to 1 mm ST-segment depression.
- Change in % of time variation from baseline to 1 mm ST-segment
depression.
- Change in time to angina.
- Change in % of time variation from baseline to Angina
- To assess the number of angina attacks/week and the number of
sublingual nitroglycerin/nitrates consumption/week.
- To assess use and changes in antianginal therapy (beta blockers,
calcium channel antagonists, nitrates, ACE-inhibitors, Ivabradine,
Trimetazidine, Nicorandil-where present in Europe) and changes in their doses, from baseline to the end of the study.

E.5.2.1

Timepoint(s) of evaluation of this end point

If not specified has to be intended at each visit when the parameter is assessed

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

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)

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

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.8.4.1

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

Albania

Russian Federation

Switzerland

Ukraine

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

Last patient 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:

490

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

950

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

790

F.4.2.2

In the whole clinical trial

1440

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)

The investigator can decide how to treat the patient after the end of the trial. All available treatments are allowed.

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

2011-11-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-09-22

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2016-01-06

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