Clinical Trials Register

Summary
EudraCT Number:	2015-004207-22
Sponsor's Protocol Code Number:	CLCZ696B2319
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-03-01
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

France - ANSM

A.2

EudraCT number

2015-004207-22

A.3

Full title of the trial

Multicenter, open-label, study to evaluate safety, tolerability, pharmacokinetics and, pharmacodynamics of LCZ696 followed by a 52-week randomized, double-blind, parallel group, active-controlled study to evaluate the efficacy and safety of LCZ696 compared with enalapril in pediatric patients from1 month to < 18 years of age with heart failure due to systemic left ventricle systolic dysfunction

Etude multicentrique, en ouvert, pour évaluer la sécurité d’emploi, la tolérance, la pharmacocinétique et la pharmacodynamique de LCZ696 (sacubitril/valsartan) suivie par une étude contrôlée de 52 semaines randomisée, en double-aveugle, en groupes parallèles pour évaluer l’efficacité et la sécurité d’emploi de LCZ696 en comparaison avec l’énalapril chez des patients pédiatriques âgés de 1 mois à moins de 18 ans atteints d’insuffisance cardiaque due à une dysfonction ventriculaire gauche systolique

A.3.1

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

Pharmacokinetics, pharmacodynamics, safety and efficacy study of LCZ696 in children (1 month to < 18 years) with heart failure

Etude pour évaluer la pharmacocinétique, la pharmacodynamique, la sécurité d’emploi et l’efficacité de LCZ696 chez des patients pédiatriques (âgés de 1 mois à moins de 18 ans) atteints d’insuffisance cardiaque

A.4.1

Sponsor's protocol code number

CLCZ696B2319

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/240/2015

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Novartis Pharma Services AG
B.1.3.4	Country	Switzerland
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 Pharma Service AG
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 Pharma S.A.S
B.5.2	Functional name of contact point	Information&Communication Médicales
B.5.3	Address:
B.5.3.1	Street Address	2 et 4 rue Lionel Terray
B.5.3.2	Town/ city	Rueil-Malmaison
B.5.3.3	Post code	92500
B.5.3.4	Country	France
B.5.4	Telephone number	+331 55476600
B.5.5	Fax number	+331 55476100
B.5.6	E-mail	icm.phfr@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	LCZ696 12.5 mg film-coated granules in capsule (4 x 3.125 mg film-coated granules)
D.3.2	Product code	LCZ696
D.3.4	Pharmaceutical form	Granules
D.3.4.1	Specific paediatric formulation	Yes
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	sacubitril/valsartan
D.3.9.3	Other descriptive name	SACUBITRIL VALSARTAN
D.3.9.4	EV Substance Code	SUB171905
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	12.5
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.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	Entresto
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
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	LCZ696 50 mg
D.3.2	Product code	LCZ696
D.3.4	Pharmaceutical form	Film-coated 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	sacubitril/valsartan
D.3.9.3	Other descriptive name	SACUBITRIL VALSARTAN
D.3.9.4	EV Substance Code	SUB171905
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	50
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	Entresto
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
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	LCZ696 100 mg
D.3.2	Product code	LCZ696
D.3.4	Pharmaceutical form	Film-coated 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	sacubitril/valsartan
D.3.9.3	Other descriptive name	SACUBITRIL VALSARTAN
D.3.9.4	EV Substance Code	SUB171905
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	100
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	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	Entresto
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
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	LCZ696 200 mg
D.3.2	Product code	LCZ696
D.3.4	Pharmaceutical form	Film-coated 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	sacubitril/valsartan
D.3.9.3	Other descriptive name	SACUBITRIL VALSARTAN
D.3.9.4	EV Substance Code	SUB171905
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: 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	Enalapril
D.2.1.1.2	Name of the Marketing Authorisation holder	Lek Pharmaceuticals d.d.
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.3.1	Product name	Enalapril 2.5 mg
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	enalapril
D.3.9.3	Other descriptive name	ENALAPRIL MALEATE
D.3.9.4	EV Substance Code	SUB01884MIG
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	2.5
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.IMP: 6
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	Enalapril
D.2.1.1.2	Name of the Marketing Authorisation holder	Hexal AG
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.3.1	Product name	Enalapril 5 mg
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	enalapril
D.3.9.3	Other descriptive name	ENALAPRIL MALEATE
D.3.9.4	EV Substance Code	SUB01884MIG
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.IMP: 7
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	Enalapril
D.2.1.1.2	Name of the Marketing Authorisation holder	Hexal AG
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.3.1	Product name	Enalapril 10 mg
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	enalapril
D.3.9.3	Other descriptive name	ENALAPRIL MALEATE
D.3.9.4	EV Substance Code	SUB01884MIG
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	10
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: 8
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	LCZ696 31.25 mg film-coated granules in capsule (10 x 3.125 mg film-coated granules)
D.3.2	Product code	LCZ696
D.3.4	Pharmaceutical form	Granules
D.3.4.1	Specific paediatric formulation	Yes
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	sacubitril/valsartan
D.3.9.3	Other descriptive name	SACUBITRIL VALSARTAN
D.3.9.4	EV Substance Code	SUB171905
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	31.25
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.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	Granules
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
D.8 Placebo: 3
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: 4
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: 5
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: 6
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: 7
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: 8
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Granules
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

Pediatric heart failure 1 month to <18 years old

Insuffisance cardiaque chez des patients pédiatriques âgés de 1 mois à moins de 18 ans

E.1.1.1

Medical condition in easily understood language

Pediatric heart failure (HF)

Insuffisance cardiaque (IC)

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	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10019279
E.1.2	Term	Heart failure
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

This study consist of two parts (Part 1 and Part 2).
Part 1: to evaluate the way the body absorbs, distributes and removes the drug LCZ696. This will help determine the proper dose of LCZ696 for Part 2 of the study.
Part 2: to compare the effectiveness and safety of LCZ696 with enalapril in pediatric heart failure patients over 52 weeks of treatment.

Cette étude comporte deux parties.
Partie 1 : L'objectif principal consiste à déterminer la façon dont le corps absorbe, distribue et éliminele medicament LCZ696. Cela aidera à déterminer la dose appropriée de LCZ696 pour la partie 2 de l'étude.
Partie 2 : L'objectif principal consiste à comparer l'efficacité et la sécurité de LCZ696 avec énalapril chez les patients pédiatriques présentant une insuffisance cardiaque pendant 52 semaines de traitement.

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Chronic heart failure resulting from left ventricular systolic dysfunction, and receiving chronic HF therapy (if not newly diagnosed)
- NYHA classification II-IV (older children: 6 to <18 years old) or Ross CHF classification II-IV (younger children: < 6 years old)
- Systemic left ventricular ejection fraction ≤ 40% or fractional shortening ≤20%
- For Part 1 PK/PD, patients must be treated with an ACEI (Angiotensin converting enzyme inhibitor) or ARB (Angiotensin receptor blockers) prior to screening. For Part 1 PK/PD, patients in Group 1 and 2 must be currently treated with the dose equivalent of at least enalapril 0.2 mg/kg prior to the LCZ696 3.1 mg/kg single dose assessment.
- Biventricular physiology with systemic left ventricle

- Insuffisance cardiaque chronique résultant d'une dysfonction systolique ventriculaire gauche, et bénéficiant d'un traitement de l'IC chronique (s'il ne s'agit pas de cas nouvellement diagnostiqués)
- Classification II-IV NYHA (enfants plus âgés : âgés de 6 jusqu'à moins de 18 ans) ou classification II-IV Ross IC (enfants plus jeunes : âgés de moins de 6 ans)
- Fraction d'éjection ventriculaire gauche (FEVG) ≤ 40 % ou fraction de raccourcissement ≤ 20 %
- Pour la Partie 1 PK/PD, les patients doivent être traités avec un IECA ou ARA avant la sélection. Pour la partie 1 PK/PD, les patients des groupes 1 et 2 doivent être couramment traités avec une dose équivalente d’énalapril d’au moins 0,2 mg/kg avant l’évaluation de la dose unique de 3,1 mg/kg de LCZ696.
- Physiologie biventriculaire avec ventricule gauche systémique

E.4

Principal exclusion criteria

- Patient with single ventricle or systemic right ventricle
- Patients listed for heart transplantation (as United Network for Organ Sharing status 1A) or hospitalized waiting for transplant (while on inotropes or with ventricular assist device)
- Sustained or symptomatic dysrhythmias uncontrolled with drug or device therapy
- Patients that have had cardiovascular surgery or percutaneous intervention to palliate or correct congenital cardiovascular malformations within 3 months of the screening visit. Patients anticipated to undergo corrective heart surgery during the 12 months after entry into Part 2.
- Patients with unoperated obstructive or severe regurgitant valvular (aortic, pulmonary, or tricuspid) disease, or significant systemic ventricular outflow obstruction or aortic arch obstruction.
- Patients with restrictive or hypertrophic cardiomyopathy
- Active myocarditis
- Renal vascular hypertension (including renal artery stenosis)
- Moderate-to severe obstructive pulmonary disease
- Serum potassium >5.3 mmol/L at Visit 1 or at Visit 301
- History of angioedema
- Allergy or hypersensitivity to ACEI / ARB
Other protocol defined inclusion/exclusion criteria may apply.

- Patients avec ventricule unique ou ventricule droit systémique
- Patients inscrits pour une transplantation cardiaque avec le statut 1A de l'UNOS (United Network for Organ Sharing) ou hospitalisés en attente de greffe (sous inotropes ou avec un dispositif d'assistance ventriculaire)
- Arythmies soutenues ou symptomatiques non contrôlées par traitement médicamenteux ou par dispositif d'assistance
- Patients ayant eu une intervention chirurgicale cardiovasculaire ou une intervention percutanée corrective pour pallier ou corriger une malformation cardiovasculaire congénitale dans les 3 mois précédant la visite de sélection. Patients pour lesquels une intervention chirurgicale cardiovasculaire est prévue dans les 12 mois suivant leur inclusion dans la partie 2.
- Patients atteints d'une fuite valvulaire sévère ou obstructive non opérée (aortique, pulmonaire ou tricuspide), ou d'une obstruction significative à l'éjection ventriculaire gauche ou d'une obstruction de l'arche aortique
- Patients atteints de cardiomyopathie restrictive ou hypertrophique
- Myocardite active
- Hypertension vasculaire rénale (incluant une sténose de l’artère rénale)
- Maladie pulmonaire obstructive modérée à sévère
- Potassium sérique > 5,3 mmol/L à la visite 1 ou visite 301
- Antécédents d'angiœdème
- Allergie ou hypersensibilité aux IECA/ARA
D'autres critères d'inclusion ou d'exclusion définis dans le protocole peuvent s'appliquer

E.5 End points

E.5.1

Primary end point(s)

Part 1:
- Pharmacokinetics of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Maximum drug concentration in plasma (Cmax). Cmax will be determined for LCZ696 analytes (sacubitril, LBQ657, and valsartan) by using non-compartmental methods.
- Pharmacokinetics of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Time to maximum plasma concentration (Tmax). Tmax will be determined for LCZ696 analytes (sacubitril, LBQ657, and valsartan) by using non-compartmental methods.
- Pharmacokinetics of LCZ696 analytes (sacubitril, LBQ657, and valsartan): area under the plasma concentration-time curve from time zero to infinity (AUCinf) and area under the plasma concentration-time curve from time zero to last (AUClast). AUCinf and AUClast will be determined for LCZ696 analytes (sacubitril, LBQ657, and valsartan) by using non-compartmental methods.
- Pharmacokinetics of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Clearance from plasma (CL/F). CL/F will be determined for LCZ696 analytes (sacubitril, LBQ657, and valsartan) by using non-compartmental methods.
- Pharmacokinetics of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Time required to drug concentration to decrease by half (T 1/2). T 1/2 will be determined for LCZ696 analytes (sacubitril, LBQ657, and valsartan) by using non-compartmental methods
- Pharmacodynamics of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Plasma B-type natriuretic peptide (BNP), plasma N-terminal pro-brain natriuretic peptide (NTproBNP). The 24 hour post dose is optional depending on blood volume restrictions.
- Pharmacodynamics of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Plasma cyclic guanosine monophosphate (cGMP). The 24 hour post dose is optional depending on blood volume restrictions.
- Pharmacodynamics of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Urine cGMP. The urine samples will be collected at pre-dose and once between 4 to 8 hours post dosing.

Part 2:
- Percentage of patients falling into each category based on global ranking. The global ranking is based on clinical events such as death, listing for urgent heart transplant, mechanical life support requirement at end of study, worsening heart failure (HF), New York Heart Association (NYHA)/Ross, Patient Global Impression of Severity (PGIS), Pediatric Quality of Life Inventory (PedsQL) physical functioning domain. The primary endpoint will be derived based on 5 categories ranking worst to best outcome.

Partie 1:
- La pharmacocinétique des analytes de LCZ696 (sacubitril, LBQ657 et valsartan): La concentration maximale du médicament dans le plasma (Cmax). Cmax sera déterminé pour les analytes de LCZ696 (sacubitril, LBQ657 et valsartan) en utilisant des méthodes non-compartimentées.
- La pharmacocinétique des analytes de LCZ696 (sacubitril, LBQ657 et valsartan): Le temps de la concentration plasmatique maximale (Tmax). Tmax sera déterminé pour les analytes de LCZ696 (sacubitril, LBQ657 et valsartan) en utilisant des méthodes non-compartimentées.
- La pharmacocinétique des analytes de LCZ696 (sacubitril, LBQ657 et valsartan): L'aire sous la courbe des concentration plasmatique-temps de temps zéro à l'infini (ASCinf) et l'aire sous la courbe de concentration plasmatique-temps du temps zéro à la dernière (AUClast). AUCinf et AUClast seront déterminés pour les analytes de LCZ696 (sacubitril, LBQ657 et valsartan) en utilisant des méthodes non-compartimentées.
- La pharmacocinétique des analytes de LCZ696 (sacubitril, LBQ657 et valsartan): La clairance plasmatique (CL/F). La CL/F sera déterminée pour les analytes de LCZ696 (sacubitril, LBQ657 et valsartan) en utilisant des méthodes non-compartimentées.
- La pharmacocinétique des analytes de LCZ696 (sacubitril, LBQ657 et valsartan): Le temps nécessaire à la concentration du médicament pour diminuer de moitié (T 1/2). Le T 1/2 sera déterminé pour les analytes de LCZ696 (sacubitril, LBQ657 et valsartan) en utilisant des méthodes non-compartimentées.
- La pharmacodynamique des analytes de LCZ696 (sacubitril, LBQ657 et valsartan): Le peptide natriurétique de type B (BNP) du plasma, le peptide natriurétique pro-encéphalique N-terminal (NTproBNP) du plasma. La dose post 24 heures est facultative, en fonction des restrictions du volume de sang.
- La pharmacodynamique des analytes de LCZ696 (sacubitril, LBQ657 et valsartan): La guanosine monophosphate cyclique (GMPc) du plasma. La dose post 24 heures est facultative, en fonction des restrictions du volume de sang.
- La pharmacodynamique des analytes de LCZ696 (sacubitril, LBQ657 et valsartan): cGMP urinaire. Les échantillons d'urine seront prélevés à pré-dose et une fois entre 4 et 8 heures après l'administration.

Partie 2 :
Pourcentage de patients inclus dans chaque catégorie sur la base du classement mondial. Le classement mondial est basé sur des événements cliniques tels que la mort, l'annonce pour transplantation cardiaque urgente, la nécessité de soutien vital à la fin de l'étude, l'aggravation de l'insuffisance cardiaque (IC), New York Heart Association (NYHA) / Ross, Patient Global Impression of Severity (PGIS), Pediatric Quality of Life Pediatric Inventory (PedsQL) domaine du fonctionnement physique. Le critère principal sera dérivé selon5 catégories de classement du pire au meilleur résultat.

E.5.1.1

Timepoint(s) of evaluation of this end point

Part 1:
Phramacokinetics: Time Frame: 0, 0.5, 1, 2, 4, 8, 10, and optional 24 hours post dosing.
Pharmacodynamics:
- of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Plasma Nterminal pro-brain natriuretic peptide (NTproBNP):
Time Frame: 0 and optional 24 hours post dosing.
The 24 hour post dose is optional depending on blood volume restrictions.
- of LCZ696 analytes: Plasma plasma B-type natriuretic peptide (BNP):
Time Frame: 0, 4, 8 hour post dosing.
- of LCZ696 analytes: Plasma cyclic guanosine monophosphate (cGMP):
Time Frame: 0, 4, 8 hour post dosing.
- of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Urine cGMP:
Time Frame: 0, Between 4 and 8 hours post dose.
An urine sample will be collected at pre-dose and between 4 to 8 hours
Part 2: Up to 52 weeks

Partie 1:
Pharmacocinétique: Délai: 0, 0.5, 1, 2, 4, 8, 10 et optionnel 24 heures après l'administration.
Pharmacodynamique:
- des analytes de LCZ696 (sacubitril, LBQ657, and valsartan) : le peptide natriurétique pro-encéphalique N-terminal (NTproBNP) du plasma:
Délai: 0 et optionnel 24 heures après l'administration.
- des analytes de LCZ696: Le peptide natriurétique de type B (BNP) du plasma:
Délai: 0, 4, 8 heures après l'administration.
- des analytes de LCZ696: La guanosine monophosphate cyclique (GMPc) du plasma:
Délai: 0, 4, 8 heures après l'administration.
- des analytes de LCZ696 (sacubitril, LBQ657 et valsartan): cGMP urinaire:
Délai: 0, entre 4 et 8 heures après l'administration.

Partie 2: Jusqu'à 52 semaines

E.5.2

Secondary end point(s)

Part 1: To assess the safety and tolerability of LCZ696 in pediatric patients with heart failure
Part 2:
- Time to first occurrence of Category 1 or Category 2 event. Category 1: Death; United Network for Organ Sharing (UNOS) status 1A listing for heart transplant or equivalent; VAD/ECMO/mechanical ventilation/intra-aortic balloon pump requirement for life support at end of study. Category 2: Worsening HF (WHF); defined by signs and symptoms of WHF that requires an intensification of HF therapy
- Change from baseline in NYHA/Ross functional class. NYHA/Ross functional class will be compared through 52 weeks of double-blind treatment
- Change from baseline in Patient Global impression of severity score (PGIS) scale.
PGIS scale will be compared for LCZ696 and enalapril through 52 weeks of double-blind treatment
- Population PK of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Clearance from plasma in steady state (CL,ss). The steady state population PK parameter clearance will be estimated to be used in model.
- Population PK of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Volume of distribution in steady state. The steady state population PK parameter volume of distribution will be estimated to be used in model.
- Population PK of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Absorption rate constant in steady state (Ka,ss). The steady state population PK parameter Ka will be estimated to be used in model.
- Population PK of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Time required to drug concentration to decrease by half in steady state (T 1/2,ss). The steady state population PK parameter T 1/2 will be estimated to be used in model.
- Population PK of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Maximum drug concentration in plasma at steady state (Cmax,ss). The steady state population PK parameter Cmax will be estimated to be used in model.
- Population PK of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Lowest plasma concentration observed during a dosing interval at steady state (Cmin,ss). The steady state population PK parameter Cmin will be estimated to be used in model.
- Population PK of LCZ696 analytes (sacubitril, LBQ657, and valsartan): area under the plasma concentration-time curve from time zero to the end of the dosing interval tau at steady state (AUCtau,ss). The steady state population PK parameter AUC will be estimated to be used in model.

Partie 1 : Evaluer la sécurité et la tolérabilité du LCZ696 chez les patients pédiatriques atteints d'insuffisance cardiaque

Part 2:
- Le temps de la première survenue d’un événement de catégorie 1 ou 2. Categorie 1: mort; United Network for Organ Sharing (UNOS) état 1A pour transplantation cardiaque ou équivalent; VAD/ECMO/ ventilation mécanique / exigence de pompe à ballonnet intra-aortique pour le soutien de vie à la fin de l'étude. Categorie 2: Aggravation de l’IC (AIC); défini par des signes et des symptômes de AIC qui nécessite une intensification de la thérapie IC
- Changement du niveau de référence de la classe fonctionnelle NYHA / Ross. La classe fonctionnelle NYHA / Ross sera comparée pendant 52 semaines de traitement en double aveugle
- Changement du niveau de référence de l’échelle Patient Global Impression of Severity Score (PGIS). L’échelle PGIS sera comparée pour LCZ696 et énalapril pendant 52 semaines de traitement en double aveugle
- Population PK des analytes de LCZ696 (sacubitril, LBQ657 et valsartan): Clairance plasmatique à l'état d'équilibre (CL,ss). Le paramètre à l'état d'équilibre de la clairance sera estimé pour être utilisé comme modèle.
- Population PK des analytes de LCZ696 (sacubitril, LBQ657 et valsartan): volume de distribution à l'état d'équilibre. Le paramètre à l'état d'équilibre du volume de distribution sera estimé pour être utilisé comme modèle.
- Population PK des analytes de LCZ696 (sacubitril, LBQ657 et valsartan): constante du taux d'absorption à l'état d'équilibre (Ka,ss). Le paramètre à l'état d'équilibre Ka sera estimé pour être utilisé comme modèle.
- Population PK des analytes de LCZ696 (sacubitril, LBQ657 et valsartan): temps nécessaire à la concentration du médicament pour diminuer de moitié à l'état d'équilibre (T ½, ss). Le paramètre à l'état d'équilibre T ½ sera estimé pour être utilisé comme modèle.
- Population PK des analytes de LCZ696 (sacubitril, LBQ657 et valsartan): concentration de médicament maximale dans le plasma à l'état d'équilibre (Cmax, ss). Le paramètre à l'état d'équilibre Cmax sera estimé pour être utilisé comme modèle.
- Population PK des analytes de LCZ696 (sacubitril, LBQ657 et valsartan) : plus basse concentration plasmatique pendant un intervalle de dosage à l'état d'équilibre (Cmin, ss). Le paramètre à l'état d'équilibre Cmin sera estimé pour être utilisé comme modèle.
- Population PK des analytes de LCZ696 (sacubitril, LBQ657 et valsartan): aire sous la courbe du temps de concentration plasmatique de l'instant zéro à la fin de l'intervalle de dosage tau à l'état d'équilibre (AUCtau, ss). Le paramètre à l'état d'équilibre AUC sera estimé pour être utilisé comme modèle.

E.5.2.1

Timepoint(s) of evaluation of this end point

- Time to first occurrence of Cat 1 or Cat 2 event: 52 weeks.
- Change from baseline in NYHA/Ross functional class: Baseline to 52 weeks.
- Change from baseline in (PGIS) scale: Baseline to 52 weeks.
- Population PK of LCZ696 analytes: Clearance from plasma in steady state (CL,ss), Volume of distribution in steady state, Absorption rate constant in steady state (Ka,ss), Time required to drug concentration to decrease by half in steady state (T 1/2,ss), Maximum drug concentration in plasma at steady state (Cmax,ss), Lowest plasma concentration observed during a dosing interval at steady state (Cmin,ss), area under the plasma concentration-time curve from time zero to the end of the dosing interval tau at steady state (AUCtau,ss): Week 2, 12, 52.

- Temps à la première survenue d’un événement de Cat 1 ou Cat 2: 52 semaines.
- Changement du niveau de référence de la classe fonctionnelle NYHA/ Ross: Baseline à 52 semaines.
- Changement du niveau de référence de l’échelle (PGIS): Baseline à 52 semaines.
- Population PK des analytes de LCZ696: clairance plasmatique (CL,ss), volume de distribution, constante du taux d'absorption (Ka,ss), temps nécessaire à la concentration du médicament pour diminuer de moitié (T 1/2,ss), concentration de médicament maximale dans le plasma (Cmax,ss), plus basse concentration plasmatique pendant un intervalle de dosage (Cmin,ss), aire sous la courbe du temps de concentration plasmatique de l'instant zéro à la fin de l'intervalle de dosage tau (AUCtau,ss): Semaine 2, 12, 52.

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

Yes

E.6.7

Pharmacodynamic

Yes

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)

Yes

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

Yes

E.8.2.3.1

Comparator description

Part 1 is open label

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

Australia

Austria

Belgium

Brazil

Bulgaria

Canada

China

Croatia

Czech Republic

Egypt

Finland

France

Germany

Hungary

India

Israel

Italy

Japan

Korea, Republic of

Lebanon

Malaysia

Netherlands

Norway

Philippines

Poland

Russian Federation

Saudi Arabia

Singapore

Slovakia

South Africa

Spain

Sweden

Switzerland

Taiwan

Thailand

Turkey

United Arab Emirates

United Kingdom

United States

Jordan

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

A patient will be considered to have completed the study when the patient has completed the last visit planned in the protocol.

On considère qu'un patient a terminé l'étude quand il a effectué la dernière visite prevue dans le protocole.

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

Yes

F.1.1

Number of subjects for this age range:

360

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)

Yes

F.1.1.4.1

Number of subjects for this age range:

120

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

120

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

120

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Written informed consent by parent(s)/legal guardian(s) for the patient must be obtained before any study-specific assessment is performed. A consent or assent may also be required for some patients depending upon their age and local requirements.

Le consentement éclairé des parents / du représentant légal pour le patient devra être obtenu avant la réalisation de toute évaluation de l'étude.Le consentement peut aussi être requis pour certains patients selon leur âge et les exigences locales.

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

132

F.4.2.2

In the whole clinical trial

360

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)

A patient will be considered to have completed the study when the patient has completed the last visit planned in the protocol.
Continuing care should be provided by Investigator and/or other caring physician. The patient can be placed on an ACEI or ARB for HF treatment as determined by the caring physician. Standard HF medication / treatment can started at end of study.

On considère qu'un patient a terminé l'étude quand il a effectué la dernière visite prevue dans le protocole. Des soins continus doivent être dispensés par l'investigateur ou tout autre médecin. Le patient peut être mis sous IECA ou ARA en traitement de l'insuffisance cardiaque comme prescript par le médecin. Le traitement habituel pour insuffisnce cardiaque peut commencer à la fin de l'étude.

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

2017-11-09

Ethics Committee Opinion of the trial application

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-01-03

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