Clinical Trials Register

Summary
EudraCT Number:	2011-005297-36
Sponsor's Protocol Code Number:	CSPP100A2413
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-12-07
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

Spain - AEMPS

A.2

EudraCT number

2011-005297-36

A.3

Full title of the trial

An 8-week randomized, open label, multi-center study to study to evaluate the efficacy and safety of oral aliskiren 300 mg once daily under light meal versus fasted condition in patients with hypertension

Estudio aleatorizado, abierto, multicéntrico de 8 semanas de duración para evaluar la eficacia y la seguridad de la administración por vía oral una vez al día de aliskiren 300 mg en ayunas comparado con su administración con una comida ligera en pacientes con hipertensión

A.3.1

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

A study conducted in several countries and centres to compare the efficacy and safety of an 8 week treatment of patients with high blood pressure with aliskiren 300mg given once daily in fasted state compared to fed state

Estudio de 8 semanas de duración que se realiza en varios paises y centros para comparar la eficacia y seguridad del Aliskiren 300 mg en ayunas comparado con su administración con una comida ligera en pacientes con hipertensión

A.4.1

Sponsor's protocol code number

CSPP100A2413

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 Farmaceutica SA
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 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 Farmaceutica SA
B.5.2	Functional name of contact point	Inmaculada Bosch Tirau
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	0034933064342
B.5.5	Fax number	0034933064290
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	Yes
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	aliskiren
D.3.2	Product code	SPP100
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	ALISKIREN
D.3.9.1	CAS number	173334-57-1
D.3.9.2	Current sponsor code	SPP100
D.3.9.4	EV Substance Code	SUB21380
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	300
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

Hipertension esencial

E.1.1.1

Medical condition in easily understood language

high blood pressure

Hipertension

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	14.0
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 efficacy of oral aliskiren 300 mg given once daily in reduction of mean 24 hour ambulatory systolic blood pressure (maSBP) from baseline to end of 8 week treatment under light meal (fed) versus fasted conditions in patients with mild to moderate hypertension.

E.2.2

Secondary objectives of the trial

To evaluate the efficacy of oral aliskiren 300 mg in reduction of mean 24 hour maDBP from baseline to end of 8 week treatment under light meal versus fasted conditions in patients with mild to moderate hypertension
To evaluate the efficacy of oral aliskiren in reduction of the mean change of msSBP and msDBP
To evaluate the effect of a light meal versus fasted condition on aliskiren pharmacokinetics and PRA
To evaluate the proportion of patients achieving blood pressure control
To assess the proportion of patients achieving a successful response in SBP reduction
To evaluate the safety and tolerability of aliskiren under a light meal and fasted conditions in patients with mild to moderate hypertension

Evaluar la eficacia de la administración por vía oral una vez al día de aliskiren 300 mg en ayunas comparado con su administración con una comida ligera en pacientes con hipertensión de leve a moderada en la reducción del cambio medio de la presión arterial en la consulta (PASms y PADms) desde la basal hasta la finalización del tratamiento de 8 semanas de duración.Evaluar el efecto de una comida ligera en comparación con la administración en ayunas en la farmacocinética y la ARP de aliskiren.Evaluar la proporción de pacientes que alcanzan un control de la presión arterial (< 140/90 mmHg en la medición de la PA en la consulta) al final del tratamiento de 8 semanas de duración con una comida ligera en comparación con su administración en ayunas. Rerferirse al protocolo para ver el resto de objetivos secundarios

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients eligible for inclusion in this study have to fulfill all of the following criteria:
1. Written informed consent must be obtained before any assessment is performed
2. Male or female outpatients age ? 18 years old
3. Patients with essential hypertension, untreated or currently taking antihypertensive therapy (monotherapy or combination therapy).
4. Patients must have an office BP ? 140/90 mmHg and < 180/110 mmHg at the randomization visit and the preceding visit
5. Patients must have an absolute difference of ? 10 mmHg in both their msSBP and in their msDBP between the randomization visit and the preceding visit
6. Ability to communicate and comply with all study requirements

1. Se debe obtener el consentimiento informado escrito antes de realizar cualquier evaluación.
2. Pacientes ambulatorios hombres o mujeres de edad ? 18 años.
3. Pacientes con hipertensión esencial no tratados o que estén recibiendo actualmente tratamiento antihipertensivo (monoterapia o tratamiento de combinación).
4. Los pacientes deben tener una PA en la consulta ? 140/90 mmHg y < 180/110 mmHg en la visita de aleatorización y en la visita anterior.
5. Los pacientes deben tener una diferencia absoluta de ? 10 mmHg en la PASms y en la PADms entre la visita de aleatorización y la visita anterior.
6. Se debe ser capaz de comunicar y cumplir con todos los requisitos del estudio.

E.4

Principal exclusion criteria

Patients with any of the following physiological states or concomitant medical conditions at Visit 1, Visit 2, Optional Visit 201 or Visit 3 will be excluded from participation in the study.
1. Malignant hypertension or severe hypertension (grade 3 of WHO classification; msSBP ?180 mmHg or msDBP ?110 mmHg)
2. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases
3. History or evidence of a secondary form of hypertension, such as renal parenchymal hypertension, renovascular hypertension, coarctation of the aorta, primary hyperaldosteronism, Cushing?s disease, drug-induced hypertension, pheochromocytoma and polycystic kidney disease (PKD)
4. History of angina pectoris, myocardial infarction, coronary bypass surgery, ischemic heart disease, surgical or percutaneaous arterial intervention of any kind (coronary, carotid or peripheral intervention), stroke, TIA (transient ischemic attack), carotid artery stenosis, aortic aneurysm or peripheral arterial disease with in 6 months of Visit 1
5. Type 1 or Type 2 diabetes mellitus with fasting glycosylated hemoglobin (HbA1c) > 8%
6. Clinically significant valvular heart disease
7. Previous or current diagnosis of congestive heart failure NYHA Class II to IV
8. Second or third degree heart block without a pacemaker, potentially life threatening arrhythmia, symptomatic arrhythmia, or family history of torsade de pointe
9. Evidence of hepatic disease as determined by one of the following: ALT or AST values ? 3 x ULN at Visit 1, or a history of liver cirrhosis, hepatic encephalopathy, a history of esophageal varices, or a history of portocaval shunt
10. Evidence of renal impairment as determined by one of the following: serum creatinine >1.5 x ULN or eGFR < 30 ml/min/1.73m2 at Visit 1, a history of dialysis, or a history of nephrotic syndrome
11. Other significant laboratory findings such as anemia defined as Hb < 10 g/dL, serum sodium value < 132 mmol/L or serum potassium values <3.5 mmol/L or >5.3 mmol/L at Visit 1
12. Any surgical or medical condition which may significantly alter the absorption, distribution, metabolism or excretion of aliskiren, including but not limited to, any of the following: history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, bowel resection, gastric bypass, gastric stapling, or gastric banding, currently active, or active inflammatory bowel syndrome within 12 months prior to Visit 1, regarded as clinically meaningful by the investigator
13. Patients with active gastritis, active peptic ulcer, gastro-esophageal reflux requiring medical therapy, gastrointestinal/rectal bleeding, or urinary tract obstruction regarded as clinically meaningful by the investigator
14. Patients unwilling or unable to discontinue safely the use of current antihypertensive medications for a period up to 12 weeks, as required by the protocol. Administration of any agent indicated for the treatment of hypertension after Visit 1, with the permitted exception of those anti-hypertensive medications requiring tapering down commencing at Visit 1 and completing by Visit 2
15. History of drug or alcohol abuse within the last 1 year
16. History of angioedema, drug-related or otherwise
17. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer
18. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes
19. Any surgical or medical condition which, at the discretion of the investigator, places the patient at higher risk from his/her participation in the study, or are likely to prevent the patient from complying with the requirements of the study or completing the trial period
20. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment.
21. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL)
22. Persons directly involved in the execution of this protocol
23. Third shift or night workers or upper arm circumference of > 42 cm.
24. Any condition ? not identified in the protocol ? that in the opinion of the investigator or the sponsor Medical Monitor would confound the evaluation and interpretation of the efficacy and/or safety data
For a complete list of exclusion criteria please refer to the study protocol

1.Hipertensión maligna o hipertensión grave (grado 3 de la clasificación de la OMS; PASms ?180 mmHg o PADms ?110 mmHg)
2.Antecedentes de cáncer de cualquier sistema orgánico (salvo carcinoma cutáneo de células basales localizado), tratado o no tratado, durante los últimos 5 años, independientemente de que existan o no pruebas de recurrencia local o metástasis.
3.Antecedentes o signos de una forma secundaria de hipertensión, como la hipertensión renal parenquimatosa, hipertensión renovascular, coartación de la aorta, hiperaldosteronismo primario, enfermedad de Cushing, hipertensión provocada por fármacos, estenosis arterial renal unilateral o bilateral, feocromocitoma, enfermedad renal poliquística (ERP).
4.Antecedentes de angina de pecho, infarto de miocardio, intervención de baipás coronario, enfermedad cardiaca isquémica, intervención arterial quirúrgica o percutánea de cualquier tipo (intervención coronaria, carótida o periférica), apoplejía, AIT (ataque isquémico transitorio), estenosis de la arteria carótida, aneurisma aórtico o enfermedad arterial periférica durante los 6 meses anteriores a la visita 1.
5.Diabetes mellitus tipo 1 o tipo 2 con hemoglobina glicosiladaglucosilada en ayunas (HbA1c) > 8%.
6.Enfermedad cardiaca valvular clínicamente significativa.
7.Diagnóstico previo o actual de insuficiencia cardiaca congestiva de clase II a IV de la NYHA.
8.Bloqueo cardiaco de segundo o tercer grado sin marcapasos, arritmia que sea una posible amenaza contra la vida, arritmia sintomática o antecedentes familiares de torsade de pointes.
9.Signos de enfermedad hepática determinada por uno de los siguientes: valores de ALT o AST ? 3 x LSN en la visita 1, o antecedentes de cirrosis hepática, encefalopatía hepática, antecedentes de varices esofágicas o antecedentes de derivación portocava.
10.Signos de deterioro renal según se determina por uno de los siguientes: creatinina sérica >1,5 x LSN o VSGe < 30 ml/min/1,73m2 en la visita 1, antecedentes de diálisis, o antecedentes de síndrome nefrítico.
11.Otros hallazgos de laboratorio significativos como anemia definida como Hb < 10 g/dl, valor de sodio sérico < 132 mmol/l o valores de potasio sérico <3,5 mmol/l o >5,3 mmol/l en la visita 1.
12.Cualquier condición quirúrgica o enfermedad que altere de forma significativa la absorción, distribución, metabolismo o excreción de aliskiren, incluyendo entre otras, cualquiera de las siguientes: antecedentes de intervención mayor del tracto gastrointestinal como gastrectomía, gastroenterostomía, resección intestinal, baipás gástrico, grapado gástrico o cerclaje gástrico, actualmente activos o enfermedad inflamatoria intestinal activa durante los 12 meses anteriores a la visita 1, que el investigador considere clínicamente significativos.
13.Pacientes con gastritis activa, úlcera péptica activa, reflujo gastroesofágico que precise tratamiento médico, hemorragia gastrointestinal/rectal u obstrucción del tracto urinario considerado como clínicamente significativo por el investigador.
14.Pacientes que no deseen o sean incapaces de suspender de forma segura el uso de la medicación antihipertensiva actual durante un periodo de hasta 12 semanas, según se requiere en el protocolo. La administración de cualquier fármaco indicado para el tratamiento de la hipertensión después de la visita 1, con la excepción permitida de aquella medicación antihipertensiva que precise disminución gradual desde la visita 1 hasta la visita 2

E.5 End points

E.5.1

Primary end point(s)

24 hours mean systolic ambulatory blood pressure

reducción de la presión arterial sistólica media ambulatoria de 24 horas (PASma)

E.5.1.1

Timepoint(s) of evaluation of this end point

after 8 weeks of treatment

Despues de 8 semnas de tratamiento

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

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)

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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

Belgium

Canada

Italy

Slovakia

Spain

Taiwan

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

Last patient last visit.

La ultima visita del ultimo 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:

400

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

168

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

568

F.4.2.2

In the whole clinical trial

568

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)

normal treatment

Tratamiento habitual para esta patologia

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

2012-02-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-02-15

P. End of Trial
P.	End of Trial Status	Completed

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