Clinical Trials Register

Summary
EudraCT Number:	2011-001516-54
Sponsor's Protocol Code Number:	GS-US-259-0103
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-04-02
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2011-001516-54

A.3

Full title of the trial

A Phase 4, Randomized, Double-Blind, Placebo-Controlled, Cross-over Trial to Evaluate the Effects of Ranolazine on Myocardial Perfusion Assessed by Serial Quantitative Exercise SPECT Imaging

Studio di Fase 4, randomizzato, in doppio cieco, cross-over, controllato con placebo per valutare gli effetti di Ranolazina sulla perfusione miocardica valutata in base all`™esame di tomoscintigrafia miocardica seriale quantitativa da sforzo SPECT (Serial Quantitative Exercise SPECT Imaging)

A.3.1

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

A randomized, double-blind, placebo-controlled, cross-over trial looking at the effects of ranolazine on blood flow in the heart as assessed by nuclear imaging

Studio, randomizzato, in doppio cieco, cross-over, controllato con placebo per valutare gli effetti di Ranolazina sul flusso sanguigno misurato mediante diagnostica per immagini

A.4.1

Sponsor's protocol code number

GS-US-259-0103

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01221272

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	GILEAD SCIENCE 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	Gilead Sciences, Inc.
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	Gilead Sciences International Limited
B.5.2	Functional name of contact point	Clinical Trials Information
B.5.3	Address:
B.5.3.1	Street Address	Flowers Building, Granta Park
B.5.3.2	Town/ city	Great Abington, Cambridge
B.5.3.3	Post code	CB21 6GT
B.5.3.4	Country	Italy
B.5.4	Telephone number	+44 1223 897 496
B.5.5	Fax number	+44 1223 897 284
B.5.6	E-mail	clinical.trials@gilead.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
D.2.1.1.2	Name of the Marketing Authorisation holder	Menarini Internatonal
D.2.1.2	Country which granted the Marketing Authorisation	United States
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	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	NA
D.3.9.1	CAS number	95635-55-5
D.3.9.2	Current sponsor code	GS-9668
D.3.9.3	Other descriptive name	RANOLAZINE
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	Prolonged-release 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

Coronary artery disease

malattia arteriosa coronarica

E.1.1.1

Medical condition in easily understood language

Heart disease

malattia cardiaca

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	SOC
E.1.2	Classification code	10007541
E.1.2	Term	Cardiac disorders
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

The primary efficacy endpoint of this study is to evaluate the effect of ranolazine (versus placebo) on exercise-induced PDS by automated polar maps

Valutare gli effetti di Ranolazina in confronto al placebo sul difetto di perfusione miocardica indotto da sforzo fisico (PDS)

E.2.2

Secondary objectives of the trial

not applicable

non applicabile

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Previous clinically indicated exercise stress SPECT MPI study
showing at least 10% reversible myocardial ischemia (as
confirmed by the core nuclear laboratory) performed within
4 weeks prior to Screening
• Stable doses of ≤ 2 antianginal medications (not including
short-acting nitroglycerin)

• Una prova da sforzo con SPECT MPI indicata clinicamente che evidenzia la presenza di ischemia miocardica reversibile almeno per il 10% (confermata dagli esami condotti dal laboratorio nucleare centrale) ed eseguita entro le 4 settimane prima dello Screening
• Trattamento stabile con ≤ 2 farmaci antiangina (esclusa la nitroglicerina ’short-acting’)

E.4

Principal exclusion criteria

Left bundle branch block
• Automated implantable defibrillator and/or pacemaker
• Intervening coronary revascularization between the time of
previous clinically indicated exercise stress SPECT MPI study
and Screening
• Acute myocardial infarction within 60 days prior to Screening,
or MI with planned intervention during the duration of this
study
Unstable angina within 30 days prior to Screening
• Coronary artery bypass graft (CABG) surgery within 60 days
prior to Screening or percutaneous coronary intervention (PCI)
within 30 days prior to Screening
• Anticipated coronary revascularization during the study period
• Cerebrovascular Attack (CVA) or Transient Ischemic Attack
(TIA) within 90 days prior to Screening
• History of serious arrhythmias
• Currently in atrial fibrillation or atrial flutter
• QTc interval > 500 milliseconds
• Diagnosed as having New York Heart Association (NYHA)
Class III or IV heart failure
• Inability to exercise or exercise limitation due to other
co-morbidities that may interfere with ability to perform
required ETT
• Body Mass Index (BMI) ≥ 38 kg/m2
• Any absolute contraindications to exercise stress test

• Blocco di branca sinistra • Presenza di defibrillatore e/o pacemaker automatico impiantabile • Rivascolarizzazione coronarica effettuata tra la prova da sforzo con SPECT MPI indicato clinicamente e lo Screening • Infarto miocardico acuto nei 60 giorni antecedenti lo Screening o infarto miocardico con intervento programmato nel corso della durata dello Studio • Angina instabile nei 30 giorni antecedenti lo Screening • Intervento di bypass dell’arteria coronarica (CABG) nei 60 antecedenti lo Screening o intervento coronarico percutaneo (PCI) nei 30 giorni prima dello Screening • Rivascolarizzazione coronarica programmata durante il periodo dello studio • Evento cerebrovascolare (CVA) o attacco ischemico transitorio (TIA) nei 90 giorni antecedentilo Screening • Storia di aritmia grave • Presenza di fibrillazione atriale o flutter atriale • Intervallo QTc > 500 millisecondi • Diagnosi di insufficienza cardiaca di Classe III o IV secondo la classificazione della New York Heart Association (NYHA) • Incapacità di svolgere attività fisica o limitazione dell’attività fisica causata da altre co-morbidità che possono interferire con la capacità di eseguire l’esame ETT richiesto • Indice di massa corporea (IMC)  38 kg/m2 • Qualsiasi controindicazione assoluta all’esame da sforzo

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint of this study is to evaluate the effect of ranolazine (versus placebo) on exercise-induced PDS by automated polar maps

Effetto di ranolazine (versus placebo) sul difetto di perfusione miocardica (PDS) indotto da esercizio

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 15 and 30

al giorno 15 e al giorno 30

E.5.2

Secondary end point(s)

1. Effect of ranolazine (versus placebo) on the following SPECT MPI variables: a. Exercise-induced perfusion defect severity by automated polar maps. b. Exercise-induced reversible perfusion defect size by automated polar maps

1. Effetto di ranolazine (versus placebo) sulle variabili SPECT MPI seguenti: a. Estensione del difetto di perfusione indotto da esercizio b. Estensione del difetto di perfusione reversibile indotto da esercizio

E.5.2.1

Timepoint(s) of evaluation of this end point

Day 15 and 30

al giorno 15 e al giorno 30

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

Yes

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

Yes

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

Yes

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

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

Canada

Singapore

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

Two week safety follow up call after the last subject's last visit

due settimane dopo l'ultima visita dell'ultimo paziente (alla visita telefonica di follow up)

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

Number of subjects for this age range:

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:

107

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

107

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

214

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)

Subjects should continue concomitant antianginal medications and
should restart any medications discontinued during the screening
period after completion of all study procedures under the care of their
primary treating physician.

I soggetti, dopo aver completato tutte le procedure previste dallo stuido e sotto la supervisione del proprio medico, dovranno continuare i trattamenti concomitanti per la loro condizione clinica e ricominciare il trattamento con i farmaci interrotti durante il periodo di screening

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

2012-05-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-03-21

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2012-09-27

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