Clinical Trials Register

Summary
EudraCT Number:	2011-005297-36
Sponsor's Protocol Code Number:	CSPP100A2413
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:	2012-03-06
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2011-005297-36

A.3

Full title of the trial

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

Studio multicentrico, randomizzato, in aperto, della durata di 8 settimane per valutare l'™efficacia e la sicurezza di aliskiren 300 mg al giorno somministrato per via orale dopo un pasto leggero rispetto alla somministrazione a digiuno in pazienti con ipertensione

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

Studio condotto in diversi paesi e centri per confrontare l'efficacia e la sicurezza del trattamento con Aliskiren 300 mg somministrato una volta al giorno per via orale dopo un pasto leggero rispetto alla somministrazione a digiuno in pazienti con pressione sanguigna alta

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 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 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 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	Yes
D.2.1.1.1	Trade name	RASILEZ*30CPR RIV 300MG
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	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

Ipertensione essenziale

E.1.1.1

Medical condition in easily understood language

High blood pressure

Pressione sanguigna alta

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	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.

Valutare l’efficacia di aliskiren 300 mg nel ridurre la pressione arteriosa sistolica ambulatoria media nelle 24 ore (mean 24 hour ambulatory Systolic Blood Pressure - maSBP) dal basale alla fine di un periodo di trattamento di 8 settimane, somministrato una volta al giorno per via orale con un pasto leggero rispetto alla somministrazione a digiuno in pazienti con ipertensione da lieve a moderata.

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.

- Valutare l’efficacia di aliskiren 300 mg nel ridurre la pressione arteriosa diastolica ambulatoriale (maDBP) media nelle 24 ore dal basale alla fine di un periodo di trattamento di 8 settimane, somministrato una volta al giorno per via orale con un pasto leggero rispetto alla somministrazione a digiuno in pazienti con ipertensione da lieve a moderata; -Valutare l'efficacia di aliskiren 300 mg nel ridurre la variazione media di msSBP and msDBP; -Valutare l'effetto di un pasto leggero rispetto a condizioni di digiuno sulla farmacocinetica e PRA di aliskiren 300 mg; -Valutare la proporzione di pazienti che hanno ottenuto il controllo della pressione arteriosa; -Valutare la proporzione di pazienti che hanno ottenuto una risposta positiva nel ridurre la SBP

E.2.3

Trial contains a sub-study

E.3

Principal inclusion 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.

- Pazienti ambulatoriali di sesso maschile o femminile e di età ≥ 18 anni; - Pazienti con ipertensione essenziale, non trattati o che attualmente assumono una terapia antipertensiva (in monoterapia o in combinazione); - Pazienti con valori di pressione arteriosa misurati in ambulatorio ≥ 140/90 mmHg e < 180/110mmHg alla visita di randomizzazione e alla visita precedente; - Pazienti con una differenza assoluta ≤ 10 mmHg sia nella msSBP che nella msDBP tra la visita di randomizzazione e la visita precedente. Per maggiori dettagli consultare il paragrafo 4.1 del protocollo originale.

E.4

Principal exclusion criteria

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, druginduced 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.For a complete list of exclusion criteria please refer to the study protocol.

- Ipertensione maligna o ipertensione severa (grado 3 secondo la classificazione WHO); msSBP ≥180 mmHg o msDBP ≥110 mmHg; - Storia o evidenza di una forma di ipertensione secondaria, come ipertensione parenchimale renale, ipertensione renovascolare, coartazione dell’aorta, iperaldosteronismo secondario, malattia di Cushing, ipertensione farmaco indotta, stenosi dell’arteria renale unilaterale o bilaterale, feocromocitoma, malattia del rene policistico; - Diabete mellito di tipo 1 o 2 con emoglobina glicosilata (HbA1c) a digiuno > 8%; - Qualsiasi condizione medica o chirurgica che possa alterare in modo significativo l’assorbimento, la distribuzione, il metabolismo o l’escrezione di aliskiren, compreso, a titolo esemplificativo, uno qualsiasi dei seguenti: storia di chirurgia maggiore del tratto gastrointestinale come gastrectomia, gastroenterostomia, resezione intestinale, bypass gastrico, stapling gastrico o bendaggio gastrico, sindrome intestinale infiammatoria attualmente attiva, o attiva nei 12 mesi precedenti la Visita 1, clinicamente significativa a giudizio dello sperimentatore. Per maggiori dettagli consultare il paragrafo 4.2 del protocollo originale.

E.5 End points

E.5.1

Primary end point(s)

24 hours mean systolic ambulatory blood pressure

Pressione arteriosa sistolica ambulatoria media nelle 24 ore

E.5.1.1

Timepoint(s) of evaluation of this end point

After 8 weeks of treatment

Dopo 8 settimane di trattamento

E.5.2

Secondary end point(s)

N.A.

E.5.2.1

Timepoint(s) of evaluation of this end point

N.A.

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

E.8.1.1

Randomised