Clinical Trials Register

Summary
EudraCT Number:	2013-002306-31
Sponsor's Protocol Code Number:	CLCZ696A2320E1
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2013-11-12
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

Spain - AEMPS

A.2

EudraCT number

2013-002306-31

A.3

Full title of the trial

An open-label, long term (52 week) extension study to evaluate the safety,
tolerability, and efficacy of treatment with LCZ696 monotherapy and LCZ696 in
combination with amlodipine in patients with essential hypertension

Estudio de extensión abierto a largo plazo (52 semanas) para evaluar la seguridad, la tolerabilidad y la eficacia del tratamiento con LCZ696 en monoterapia y LCZ696 en combinación con amlodipino en pacientes con hipertensión esencial

A.3.1

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

Long term study of safety and efficacy of LCZ696 and LCZ696 combination with
amlodipine in patients with hypertension

Estudio a largo plazo para estudiar la seguridad y eficacia de LCZ696 y la de LCZ696 combinaod con amlodipino en pacientes con hipertensión.

A.4.1

Sponsor's protocol code number

CLCZ696A2320E1

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 Farmacéutica, S.A.
B.1.3.4	Country	Spain
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 Services 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 Farmacéutica, S.A.
B.5.2	Functional name of contact point	Departamento Médico (ICRO)
B.5.3	Address:
B.5.3.1	Street Address	Gran Via de les Corts Catalanes 764
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08013
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34900353036
B.5.5	Fax number	+34932479903
B.5.6	E-mail	eecc.novartis@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.3.2	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.3.8	INN - Proposed INN	NA
D.3.9.1	CAS number	936623-90-4
D.3.9.2	Current sponsor code	LCZ696
D.3.9.3	Other descriptive name	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	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	amlodipine Hexal
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	amlodipine besylate
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	NA
D.3.9.3	Other descriptive name	AMLODIPINE BESILATE
D.3.9.4	EV Substance Code	SUB12864MIG
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Essential hypertension

Hipertensión esencial

E.1.1.1

Medical condition in easily understood language

Patients with high blood pressure

Pacientes con tensión arterial elevada.

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	16.1
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 evaluate the long-term safety and tolerability of LCZ696 monotherapy and the LCZ696/amlodipine combination regimens in patients with essential hypertension after 26 and 52 weeks of treatment

Evaluar la seguridad y la tolerabilidad a largo plazo de LCZ696 en monoterapia y las pautas de combinación de LCZ696/amlodipino en pacientes con hipertensión esencial después de 26 y 52 semanas de tratamiento.

E.2.2

Secondary objectives of the trial

1. To evaluate the long term efficacy of LCZ696 and the LCZ696/amlodipine combination as measured by change in msSBP and msDBP after 26 and 52 weeks of treatment in patients with essential hypertension.
2. To evaluate the proportion of patients achieving blood pressure control with LCZ696 and the LCZ696/ amlodipine combination (msSBP <140 mmHg and msDBP <90 mmHg) after 26 and 52 weeks of treatment.
3. To evaluate the proportion of patients achieving msSBP response (< 140 mmHg or ? 20 mmHg reduction from baseline) and msDBP response (<90 mmHg or ?10 mmHg
reduction from baseline) after 26 and 52 weeks of treatment
4. To evaluate the change in pulse pressure of LCZ696 and the LCZ696/amlodipine combination treatment after 26 and 52 weeks of treatment.

1.Evaluar la eficacia a largo plazo de LCZ696 y de la combinación de LCZ696/amlodipino midiendo el cambio en la PASms y la PADms después de 26 y 52 semanas de tratamiento en pacientes con hipertensión esencial.
2. Evaluar la proporción de pacientes que alcancen un control de la presión arterial con LCZ696 y la combinación de LCZ696/ amlodipino (PADms <140 mmHg y PADms <90 mmHg) después de 26 y 52 semanas de tratamiento.
3. Evaluar la proporción de pacientes que alcancen una respuesta en la PASms (una reducción <140 mmHg o ?20 mmHg respecto a la basal) y una respuesta en la PADms (una reducción <90 mmHg o ?10 mmHg respecto a la basal) después de 26 y 52 semanas de tratamiento.
4. Evaluar el cambio en la presión de pulso del tratamiento con LCZ696 y la combinación de LCZ696/amlodipino después de 26 y 52 semanas de tratamiento.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Written informed consent for the extension must be obtained before any assessment is performed.
2. Patients who have successfully completed protocol CLCZ696A2320 and are able to safely continue into the open-label extension as judged by the investigator.

1. El consentimiento informado por escrito de la extensión se debe obtener antes de realizar cualquier evaluación.
2. Pacientes que hayan completado con éxito el protocolo CLCZ696A2320 y que sean capaces de continuar de forma segura en la extensión abierta según el criterio del investigador

E.4

Principal exclusion criteria

1. Patients who experienced a serious drug-related adverse event in study CLCZ696A2320.
2. Patients who develop a condition during the core study that would have excluded them from participation in the core study.
3. Patients with hypersensitivity to thiazide diuretics.

1. Pacientes que hayan experimentado un acontecimiento adverso grave relacionado con el fármaco en el estudio CLCZ696A2320.
2. Pacientes que desarrollen una condición durante el estudio principal que les pueda excluir de participar en el estudio principal (véase el Anexo 1 Criterios de exclusión del protocolo CLZ696A2320).
3. Pacientes con hipersensibilidad a los diuréticos tiazídicos.

E.5 End points

E.5.1

Primary end point(s)

Number of Adverse Events and Serious Adverse Events
reported

Número de acontecimientos adversos y acontecimientos adversos reportados.

E.5.1.1

Timepoint(s) of evaluation of this end point

26 weeks and 52 weeks

26 semanas y 52 semanas

E.5.2

Secondary end point(s)

1. Change from baseline in mean sitting systolic blood pressure
2. Change from baseline in mean sitting diastolic blood pressure
3. Percentage of patients achieving blood pressure control
4. Percentage of patients achieving successful systolic blood pressure response
5. Percentage of patients achieving successful diastolic
blood pressure response
6. Percentage of patients achieving successful diastolic blood pressure response

1. Cambio en la presión arterial sistólica media en sedestación (PASms) respecto a la basal.
2. Cambio en la presión arterial diastólica media en sedestación (PADms) respecto a la basal.
3. Cambio en la presión de pulso media en sedestación (PPms) respecto a la basal.
4. Proporción de pacientes que alcancen un control de la presión arterial (PASms/PADms < 140/90 mmHg).
5. Proporción de pacientes que alcancen una respuesta en la PASms (reducción <140 mmHg o ?20 mmHg respecto a la basal).
6. Proporción de pacientes que alcancen una respuesta en la PADms (reducción <90 mmHg o ?10 mmHg respecto a la basal).

E.5.2.1

Timepoint(s) of evaluation of this end point

26 weeks and 52 weeks for all end points

26 semanas y 52 semanas para todos los endpoints.

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)

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

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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

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

Dominican Republic

Ecuador

Guatemala

Thailand

Mexico

Panama

Peru

Philippines

South Africa

Vietnam

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

Última visita del último paciente

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:

476

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

124

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

156

F.4.2.2

In the whole clinical trial

600

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None.

Ninguno.

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

2014-01-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-01-14

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2014-06-24

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