Clinical Trials Register

Summary
EudraCT Number:	2012-002899-14
Sponsor's Protocol Code Number:	CLCZ696A2216
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:	2012-12-11
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

2012-002899-14

A.3

Full title of the trial

A randomized, double-blind, active-controlled, multicenter, 52-week study to evaluate the safety and efficacy of an LCZ696 regimen on arterial stiffness through assessment of central blood pressure in elderly patients with essential hypertension

Studio multicentrico, randomizzato, in doppio cieco, verso controllo attivo, della durata di 52 settimane per valutare la sicurezza e l efficacia di un regime di trattamento con LCZ696 sulla rigidita' arteriosa tramite la valutazione della pressione arteriosa centrale in pazienti anziani affetti da ipertensione essenziale

A.3.1

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

Study of the safety and efficacy of LCZ696 on arterial stiffness in elderly patients with hypertension

Studio di sicurezza ed efficacia con LCZ696 in pazienti anziani con ipertensione

A.4.1

Sponsor's protocol code number

CLCZ696A2216

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	NOVARTIS FARMA
B.1.3.4	Country	Italy
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	Novartis
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	NOVARTIS FARMA
B.5.2	Functional name of contact point	Drug Regulatory Affairs
B.5.3	Address:
B.5.3.1	Street Address	Largo Umberto Boccioni, 1
B.5.3.2	Town/ city	Origgio
B.5.3.3	Post code	21040
B.5.3.4	Country	Italy
B.5.4	Telephone number	+39 02 96541
B.5.5	Fax number	+39 02 9659066
B.5.6	E-mail	info.studiclinici@novartis.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	NA
D.3.2	Product code	LCZ696
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.3.9.1	CAS number	936623-90-4
D.3.9.2	Current sponsor code	LCZ696
D.3.9.4	EV Substance Code	SUB30457
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	200
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	Comparator
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	Olmetec
D.2.1.1.2	Name of the Marketing Authorisation holder	Daichi-Sankyo KK
D.2.1.2	Country which granted the Marketing Authorisation	Japan
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	Capsule
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	OLMESARTAN
D.3.9.4	EV Substance Code	SUB20707
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	40
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	Comparator
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	Olmetec
D.2.1.1.2	Name of the Marketing Authorisation holder	Daichi-Sankyo KK
D.2.1.2	Country which granted the Marketing Authorisation	Japan
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	Capsule
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	OLMESARTAN
D.3.9.4	EV Substance Code	SUB20707
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	20
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: 4
D.1.2 and D.1.3	IMP Role	Comparator
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	ESIDREX*20CPR 25MG
D.2.1.1.2	Name of the Marketing Authorisation holder	NOVARTIS FARMA SpA
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	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	idroclorotiazide
D.3.9.2	Current sponsor code	Esidrex
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	25
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: 5
D.1.2 and D.1.3	IMP Role	Comparator
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	NORVASC*28CPR 5MG
D.2.1.1.2	Name of the Marketing Authorisation holder	PFIZER ITALIA Srl
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	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	amlodipina
D.3.9.2	Current sponsor code	Norvasc
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	5
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
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 3
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule
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

elderly Hypertensive patients

pazienti anziani con ipertensione

E.1.1.1

Medical condition in easily understood language

elderly Hypertensive patients

pazienti anziani ipertesi

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	PT
E.1.2	Classification code	10020772
E.1.2	Term	Hypertension
E.1.2	System Organ Class	10047065 - Vascular disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10015488
E.1.2	Term	Essential hypertension
E.1.2	System Organ Class	10047065 - Vascular 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 demonstrate superiority of an LCZ696 regimen compared to an olmesartan regimen, as measured by change from baseline in mean Central Aortic Systolic Blood Pressure (CASP) after 12 weeks of treatment in elderly patients with essential hypertension.

Obiettivo Primario: dimostrare la superiorità di un regime di trattamento con LCZ696 rispetto ad un regime di trattamento con olmesartan, misurata tramite la variazione rispetto al basale della pressione sistolica aortica centrale (CASP) dopo 12 settimane di trattamento in pazienti anziani con ipertensione essenziale.

E.2.2

Secondary objectives of the trial

Key Secondary Objective: To demonstrate superiority of an LCZ696 regimen compared to an olmesartan regimen, as measured by change from baseline in mean Central Pulse Pressure (CPP) after 12 weeks of treatment.

Obiettivo Secondario Principale: dimostrare la superiorità di un regime di trattamento con LCZ696 rispetto ad un regime di trattamento con olmesartan, misurata tramite la variazione rispetto al basale della pressione differenziale centrale (Central Pulse Pressure – CPP) dopo 12 settimane di terapia.

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

PHARMACOGENETIC:
Vers:original
Date:2012/07/02
Title:A randomized, double-blind, active-controlled, multicenter, 52-week study to evaluate the safety and efficacy of an LCZ696 regimen on arterial stiffness through assessment of central blood pressure in elderly patients with essential hypertension
Objectives:n.a.

FARMACOGENETICA:
Vers:original
Data:2012/07/02
Titolo:Studio multicentrico, randomizzato, in doppio cieco, verso controllo attivo, della durata di 52 settimane per valutare la sicurezza e l’efficacia di un regime di trattamento con LCZ696 sulla rigidità arteriosa tramite la valutazione della pressione arteriosa centrale in pazienti anziani affetti da ipertensione essenziale.
Obiettivi:Vi informiamo che, anche se il protocollo non prevede un sottostudio formalmente definito (ovvero strutturato con un protocollo specifico) ma una indagine complementare opzionale, la stessa viene classificata come sottostudio e quindi formalizzata nell’apposita sezione del CTA Form. Di seguito il dettaglio: • Indagine di farmacogenetica, a cui parteciperanno tutti i centri italiani coinvolti nello studio. L’eventuale non accettazione di tale sottostudio da parte del Comitato Etico e/o da parte del paziente non comprometterà in alcun modo la partecipazione allo studio principale.

E.3

Principal inclusion criteria

• Written informed consent must be obtained before any assessment is performed • Male and female patients ≥ 60 years of age. • Patients with essential hypertension, untreated or currently taking antihypertensive therapy. • Untreated patients must have an office msSBP ≥150 mmHg and <180 mmHg at Visit 101 and Visit 201 if they are newly diagnosed or have not been treated with antihypertensive drugs for the 4 weeks prior to Visit 1. • Treated patients must have an office msSBP ≥140 mmHg and <180 mmHg at Visit 102 (or Visit 103) and msSBP ≥150 mmHg and <180 mmHg at Visit 201 if they have been treated with antihypertensive drugs for the 4 weeks prior to Visit 1. • All patients must have pulse pressure >60 mmHg at Visit 201. Pulse pressure is defined as msSBP- msDBP. • Patients must have a difference in msSBP of +/-15 mmHg betweenv Visit 201 (randomization) and the visit immediately prior to Visit 201. • Patients with the ability to communicate and comply with all study requirements and demonstrate good medication compliance (≥80% compliance rate) during the run-in epoch (Epoch 2).

Consenso informato scritto ottenuto prima dell’effettuazione di qualsiasi valutazione.  Pazienti di sesso maschile e femminile di età ≥ 60 anni.  Pazienti affetti da ipertensione essenziale, non trattati o attualmente in trattamento con terapia antiipertensiva.  I pazienti non trattati devono avere una misurazione effettuata in ospedale di msSBP ≥150 mmHg e <180 mmHg alla Visita 101 e alla Visita 201 se sono pazienti di nuova diagnosi o se non sono stati trattati con farmaci antiipertensivi nelle 4 settimane precedenti la Visita 1.  I pazienti trattati devono avere una misurazione effettuata in ospedale di msSBP ≥140 mmHg e <180 mmHg alla Visita 102 (o alla Visita 103) e msSBP ≥150 mmHg e <180 mmHg alla Visita 201 se sono stati trattati con farmaci antiipertensivi nelle 4 settimane precedenti la Visita 1.  Tutti pazienti devono presentare una pressione differenziale > 60 mmHg alla Visita 201. La pressione differenziale è definita come msSBP- msDBP.  I pazienti devono presentare una differenza nella msSBP di +/-15 mmHg tra la Visita 201 (randomizzazione) e la visita immediatamente precedente alla Visita 201.

E.4

Principal exclusion criteria

Malignant or severe hypertension (grade 3 of WHO classification; msDBP ≥110 mmHg and/or msSBP ≥180 mmHg). History of angioedema, drug-related or otherwise. 4. History or evidence of a secondary form of hypertension, including but not limited to any of the following: renal parenchymal hypertension, renovascular hypertension (unilateral or bilateral renal artery stenosis), coarctation of the aorta, primary hyperaldosteronism, Cushing's disease, pheochromocytoma, polycystic kidney disease, and drug-induced hypertension. 5. Transient ischemic cerebral attack (TIA) during the 12 months prior to Visit 1 or any history of stroke. 6. History of myocardial infarction, coronary bypass surgery or any percutaneous coronary intervention (PCI) during the 12 months prior to Visit 1. 7. Current angina pectoris requiring pharmacological therapy (other than patients on a stable dose of oral or topical nitrates). 8. Type 1 or Type 2 diabetes mellitus not well controlled based on the investigator's clinical judgment. Patients currently being treated for diabetes mellitus should be on stable dose of anti-diabetic medication for at least 4 weeks prior to Visit 1. 9. Previous or current diagnosis of heart failure (NYHA Class II-IV). 10. Clinically significant valvular heart disease at Visit 1. 11. History of atrial fibrillation or atrial flutter during the 3 months prior to Visit 1, or active atrial fibrillation or atrial flutter on the ECG at Visit 101. 12. History or current diagnosis of the following cardiac abnormalities: • Second or third degree AV block without a pacemaker. • History of familial long QT syndrome or family history of torsade de pointe....

Ipertensione maligna o severa (grado 3 della classificazione WHO; msDBP ≥110 mmHg e/o msSBP ≥ 180 mmHg). Storia di angioedema, correlato o meno a farmaco.  Anamnesi o evidenza di una forma secondaria di ipertensione, compresi, a titolo esemplificativo, uno qualsiasi dei seguenti: ipertensione parenchimale renale, ipertensione renovascolare (stenosi unilaterale o bilaterale dell’arteria renale), coartazione dell’aorta, iperaldosteronismo primario, malattia di Cushing, feocromocitoma, malattia renale policistica e ipertensione farmaco indotta.  Attacco ischemico cerebrale transitorio (Transient Ischemic Attack -TIA) nei 12 mesi precedenti la Visita 1 o pregresso ictus in anamnesi.  Anamnesi di infarto miocardico, chirurgia per bypass coronarico o qualsiasi intervento percutaneo coronarico (Percutaneous Coronary Intervention - PCI) nei 12 mesi precedenti la Visita 1.  Anamnesi di fibrillazione atriale o di flutter atriale nei 3 mesi precedenti la Visita 1, o fibrillazione atriale o flutter atriale attivi all’ECG alla Visita 101.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint for this phase 2 study is change from baseline in central aortic systolic pressure (CASP) after 12 weeks of treatment with LCZ696 (4 weeks of 200 mg with an additional 8 weeks of 400 mg) or olmesartan (4 weeks of 20 mg with an additional 8 weeks of 40 mg).

L'end point primario é il cambiamento rispetto al basale della pressione sistolica dell'aorta (CASP) dopo 12 settimane con LCZ696 (4 settimane da 200 mg con addizionali 8 settimane da 400 mg) o olmesartan (4 settimane da 20 mg con addizionali 8 settimane da 40 mg).

E.5.1.1

Timepoint(s) of evaluation of this end point

primary endpoint at Week 12

12 settimane

E.5.2

Secondary end point(s)

1. Change from baseline in mean central pulse pressure 2. Change from baseline in mean aortic pulse wave velocity 3. Change from baseline in mean central aortic systolic blood pressure at 52 weeks 4. Change from baseline in mean sitting systolic blood pressure 5. Change from baseline in mean sitting diastolic blood pressure 6. Change from baseline in mean sitting pulse pressure 7. Change from baseline in mean arterial pressure 8. Change from baseline in mean 24-hour systolic blood pressure 9. Change from baseline in mean 24-hour diastolic blood pressure 10. Change from baseline in mean 24-hour ambulatory pulse pressure

 Pressioni aortiche centrali.  Pressione differenziale centrale.  Velocità dell’onda sfigmica aortica.  Pressione arteriosa misurata in ospedale.  Misurazione ambulatoria della pressione arteriosa nelle 24 ore.

E.5.2.1

Timepoint(s) of evaluation of this end point

baseline, 12 weeks, and 52 weeks (1, 2, 4, 5, 6, 7, 8, 9, 10) baseline, 52 weeks (3)

basale, 12 settimane, e 52 settimane

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

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)

Yes

E.8.2.2

Placebo

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

Argentina

Brazil

Colombia

Japan

Korea, Republic of

Taiwan

United States

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

LVLS 19/NOV/2014

LVLS 19/11/2014

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:

100

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

332

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

400

F.4.2.2

In the whole clinical trial

432

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

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

2012-11-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-11-22

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-04-08

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