Clinical Trials Register

Summary
EudraCT Number:	2008-006447-40
Sponsor's Protocol Code Number:	CSPP100A2366
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:	2009-03-10
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

2008-006447-40

A.3

Full title of the trial

A 104 week, randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate the efficacy of aliskiren on the progression of atherosclerosis in patients with coronary artery disease when added to optimal background therapy

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

CSPP100A2366

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Information not present in EudraCT
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.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	Film-coated tablet
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

Progression of atherosclerosis in patients with coronary artery disease

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10011093
E.1.2	Term	Coronary atherosclerosis

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of this study is: To evaluate the effect of aliskiren 300 mg, in addition to optimized background therapy, compared to placebo on progression of coronary atherosclerosis (defined as change from baseline in percent atheroma volume) as assessed by IVUS in patients with CAD and blood pressure in the pre-hypertensive (high normal) range with or without treatment for hypertension.

E.2.2

Secondary objectives of the trial

To evaluate the efficacy profile of aliskiren 300 mg, in addition to optimized background therapy, compared to placebo on the change in normalized total atheroma volume as assessed by IVUS. To evaluate the efficacy profile of aliskiren 300 mg, in addition to optimized background therapy, compared to placebo, by comparing the proportion of patients who demonstrate evidence of atheroma regression (defined as any reduction in percent atheroma volume from baseline) as assessed by IVUS. To evaluate the overall safety and tolerability of aliskiren 300 mg compared to placebo in patients with CAD and blood pressure in the pre-hypertensive (high normal) range with or without treatment for hypertension following 104 weeks of treatment.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients must give written informed consent before any study related assessments are performed. 2. Male and female patients &#8805; 35 years of age who are scheduled for a coronary catheterization procedure for a clinically indicated reason at Visit 1. 3. Patients with or without current treatment for hypertension must have a msSBP &#8805; 125 and &#8804; 139 mmHg and an msDBP < 90 mmHg at Visit 2. For those patients receiving treatment for hypertension, every effort should be made by the Investigator to have the patient on a stable dose (defined as dose unchanged for &#8805; 1 week) of medication prior to Visit 2. 4. Patients must have at least two of the following risk factors present at Visit 1: History of prior myocardial infarction (MI), acute coronary syndrome (ACS) or previous coronary or peripheral revascularization. No prior treatment with a statin medication. If the patient has been previously treated at any time with a statin medication, it must be for a period of &#8804; 3 months in the 12 months prior to Visit 1. HDL < 40 mg/dL (1.0 mmol/L) for men or < 50 mg/dL (1.3 mmol/L) for women OR triglycerides > 150 mg/dL (1.7 mmol/L) within 3 months of Visit 1 or at Visit 1. Microalbuminuria [defined as UACR &#8805; 30 mg/g and < 300 mg/g (&#8805; 3.4 mg/mmol and < 33.9 mg/mmol)] OR macroalbuminuria [defined as UACR &#8805; 300 mg/g and < 3000 mg/g (&#8805; 33.9 mg/mmol and < 339.3 mg/mmol)] within 3 months of Visit 1 or at Visit 1. Age > 55 years. Diagnosis of diabetes mellitus based on medical history, concomitant diabetic medications being taken at study entry OR a fasting plasma glucose (FPG) > 126 mg/dL (7.0 mmol/l ) or non fasting plasma glucose > 200 mg/dL (11.1 mmol/L) or HbA1c > 6.0 % at Visit 1. Current smoking within 4 weeks of Visit 1 or at Visit 1. History of LVH documented by ECG, echocardiogram or MRI performed &#8804; 6 months prior to Visit 1. 5. Patients must meet all of the following criteria at the qualifying coronary catheterization procedure: Entire Coronary Circulation: Angiographic evidence of coronary heart disease as defined by at least one lesion in any of the three major native coronary arteries that has > 20% reduction in lumen diameter by angiographic visual estimation or prior history of PTCA. This vessel need not be the target coronary artery for IVUS (defined below). Any vessel with previous PTCA may not be used as the target coronary artery. Left Main Coronary Artery: Must not have a > 50% reduction in lumen diameter by visual angiographic estimation. PLS SEE PROTOCOL

E.4

Principal exclusion criteria

1. Baseline IVUS study determined to be of unacceptable quality by the IVUS Core laboratory in accordance with the lab manual guidelines for acquisition and analysis of IVUS imaging prior to Visit 2. 2. Patients requiring continued treatment with any 2 of the following classes of medications at Visit 1 or Visit 2: ACEIs, ARBs, aldosterone receptor blockers or a direct renin inhibitor. 3. Patients with clinically significant heart disease, which in the opinion of the Investigator is likely to require coronary bypass surgery, PCI in the target vessel, surgical repair, ventricular assist device placement, cardiac transplantation, or require intra-aortic balloon pump support during the duration of the study. 4. Patients who experience restenosis, a myocardial infarction or suspected myocardial infarction between the baseline IVUS (Visit 1) and Visit 2 can only be entered into the single-blind period of the study if the affected vessel is not the coronary artery designated as the “target vessel” at the baseline IVUS study. If the target vessel is involved, the patient must be discontinued from the screening phase of the study prior to Visit 2. 5. Previous or current diagnosis of heart failure (NYHA Class IV) or a documented left ventricular ejection fraction (LVEF) of < 25% as determined by contrast left ventriculography, radionuclide ventriculography or echocardiography. The absence of an LVEF measurement in a patient without a previous or current diagnosis of heart failure does not prohibit entry into the study. 6. Patients with evidence of cardiac electrophysiologic instability including a history of uncontrolled ventricular arrhythmias, uncontrolled atrial fibrillation/flutter or uncontrolled supraventricular tachycardia with a ventricular response heart rate of > 100 beats per minute at rest within 4 weeks prior to Visit 1. 7. Coronary artery bypass graft surgery &#8804; 6 weeks of the date of the qualifying IVUS procedure. 8. Evidence of renal impairment as determined by any one of the following: Estimated Glomerular Filtration Rate (eGFR) < 40 ml/min/1.73 m2 using the MDRD formula at Visit 1 and Visit 2. A history of dialysis, macroalbuminuria (defined as a UACR &#8805; 3000 mg/g) or nephrotic syndrome. 9. History or evidence of a secondary form of hypertension. 10. Known Keith-Wagener grade III or IV hypertensive retinopathy. 11. History of hypertensive encephalopathy, cerebrovascular accident or transient ischemic cerebral attack (TIA) within 12 months of study entry. PLS SEE PROTOCOL

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint variable of this study is the change from baseline in percent atheroma volume (PAV)for all matched slices of anatomically comparable segments of the target coronary artery as assessed by IVUS evaluation after 104 weeks of treatment (single-blind and double-blind)

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

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)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

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

Information not present in EudraCT

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

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

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

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2009-03-10.	Yes
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	48
F.4.2	For a multinational trial
F.4.2.1	In the EEA	226
F.4.2.2	In the whole clinical trial	592

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

2009-02-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-02-05

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-01-31

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