Clinical Trials Register

Summary
EudraCT Number:	2009-017029-20
Sponsor's Protocol Code Number:	CSPP100A2365E1
Clinical Trial Type:	Outside EU/EEA
Date on which this record was first entered in the EudraCT database:	2012-03-14
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
H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED

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A. Protocol Information

A.2

EudraCT number

2009-017029-20

A.3

Full title of the trial

A multicenter, double-blind, randomized, 52 week extension study to evaluate the long term safety,
tolerability and efficacy of aliskiren compared to enalapril in pediatric hypertensive patients 6-17 years of
age

A.3.1

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

A study examining the long term safety and efficacy of the drug aliskiren compared to the drug enalapril, in the treatment of high blood pressure in children 6-17 years old

A.4.1

Sponsor's protocol code number

CSPP100A2365E1

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/237/2011

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 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 Pharma Services AG
B.5.2	Functional name of contact point	Clinical Trial Information Desk
B.5.3	Address:
B.5.3.1	Street Address	Forum 1, Novartis Campus
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4056
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	+41613241111
B.5.5	Fax number	+41613248001
B.5.6	E-mail	clinicaltrial.enquiries@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	Aliskiren
D.3.2	Product code	SPP100
D.3.4	Pharmaceutical form	Film-coated tablet
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	ALISKIREN
D.3.9.1	CAS number	173334-57-1
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	up to
D.3.10.3	Concentration number	600 mg
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	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.2.1.2	Country which granted the Marketing Authorisation	Slovenia
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
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.3.9.1	CAS number	75847-73-3
D.3.9.4	EV Substance Code	SUB06514MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	40
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	Film-coated tablet
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	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

Hypertension

E.1.1.1

Medical condition in easily understood language

Hypertension (high blood pressure)

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	10020772
E.1.2	Term	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 safety and tolerability of long term administration of aliskiren compared to enalapril in
hypertensive children aged 6-17 years old (age at baseline in Study CSPP100A2365)

E.2.2

Secondary objectives of the trial

• To evaluate the efficacy (mean sitting systolic blood pressure reduction) of long-term administration of aliskiren compared to enalapril in hypertensive children aged 6-17 years old (age at baseline in Study CSPP100A2365) by testing the hypothesis of non-inferiority of aliskiren to enalapril
• To evaluate the efficacy (mean sitting diastolic blood pressure reduction) of long-term administration of aliskiren compared to enalapril in hypertensive children aged 6-17 years old (age at baseline in Study CSPP100A2365)
• To evaluate the efficacy as assessed by calculated mean arterial pressure (MAP), of longterm administration of aliskiren compared to enalapril in hypertensive children 6 to 17 years old (age at baseline in Study CSPP100A2365)

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:
• Informed consent form (approved by the Institutional Review Board (IRB)/Independent Ethics Committee (IEC)) signed by the parent(s)/legal guardian(s), after the purpose and nature of the investigation has been clearly explained to the parents and the patient, and prior to any study procedure for the extension study. An assent may be required for some patients depending upon their age and the local requirements regarding assents.
• Male or female, ages 6-17 years old, i.e. age at Visit 2 (randomization), in study CSPP100A2365, with a documented diagnosis of hypertension as defined in the NHLBI 4th Report 2004
• msSBP (mean of 3 systolic blood pressure measurements) must be ≥ 95th percentile for age, gender and height, at Visit 2 (randomization), in study CSPP100A2365
• Must be ≥ 20 kg and ≤ 150 kg at Visit 2 (randomization), in study CSPP100A2365
• Must be able to swallow minitablets (2mm in diameter) administered in soft food
• Successful completion of Phase 1 (dose response phase) and at least 1 week of Phase 2 (placebo withdrawal phase) of the CSPP100A2365 protocol, with no serious and drug-related adverse event(s).

E.4

Principal exclusion criteria

• Patients who experienced any adverse event(s) considered serious and drug-related, in study CSPP100A2365, are excluded from participation in study CSPP100A2365E1
• Any clinically significant abnormalities or clinically noteworthy abnormal laboratory values (other than those relating to renal function) at Visit 2 baseline (CSPP100A2365), including but not limited to the following:
• AST/SGOT or ALT/SGPT >3 times the upper limit of the reference range
• Total bilirubin > 2 times the upper limit of the reference range
• Creatinine clearance < 30 mL/min/1.73m² (calculated using Modified Schwartz formula to estimate glomerular filtration rate [GFR]), based on based on the serum Creatinine concentration obtained at the screening visit
• WBC count < 3000/mm³
• Platelet count < 100,000/mm³
• Serum potassium > 5.2 mEq/L
• Renal artery stenosis
• History of angioedema
• Current diagnosis of heart failure (NYHA Class II-IV) or history of cardiomyopathy or obstructive valvular disease
• msSBP ≥ 25% above the 95th percentile
• Second or third degree heart block without a pacemaker
• Atrial fibrillation or atrial flutter at Visit 1 or 6 of CSPP100A2365, or potentially life threatening, or any symptomatic arrhythmia during the 12 months prior to Visit 1 of CSPP100A2365
• Previous solid organ transplantation
• Patient receiving immunosuppressant medication (e.g. cyclosporine, MMF, etc) other than oral/topical steroids, for any medical condition
• Human immunodeficiency virus (HIV) by history and/or the patient is concomitantly
receiving anti-retroviral therapy for the treatment of HIV
• Any clinically significant unstable medical condition or chronic disease that would put the patient at risk of experiencing an adverse event associated with the expected pharmacodynamic effects of the study medication
• Any surgical or medical condition or concomitant medication which might significantly
alter the absorption, distribution, metabolism, or excretion of study medication including, but not limited to, any of the following:
• History of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection
• Currently active or previously active inflammatory bowel disease during the 12 months prior to Visit 1 of CSPP100A2365
• Currently active gastritis, duodenal or gastric ulcers, or gastrointestinal/rectal bleeding during the 3 months prior to Visit 1 of CSPP100A2365
• Active pancreatic injury, pancreatitis or evidence of impaired pancreatic
function/injury as indicated by medical history of abnormal lipase or amylase
• History of hepatic encephalopathy, a history of esophageal varices, or a history of portocaval shunt
• Current obstruction of the urinary tract or difficulty in voiding due to mechanical or inflammatory
conditions which is likely to require intervention during the course of the study or is regarded as clinically
meaningful by the investigator
• Current treatment with cyclosporine, atorvastatin, cholestyramine or colestipol resins, monoamine oxidase (MAO) inhibitors, ketoconazole, itraconazole or antiarrhythmic medications (other than digoxin)

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

E.5 End points

E.5.1

Primary end point(s)

To assess long term safety of aliskiren compared to enalapril

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline, end of study

E.5.2

Secondary end point(s)

To assess long term efficacy of aliskiren compared to enalapril

E.5.2.1

Timepoint(s) of evaluation of this end point

Baseline, end of study

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)

Yes

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

Will this trial be conducted at a single site globally?

E.8.4

Will this trial be conducted at multiple sites globally?

Yes

E.8.6 Trial involving sites outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

Specify the countries outside of the EEA in which trial sites are planned

Turkey

United States

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

LVLS

E.8.9 Initial estimate of the duration of the trial

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

Yes

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

110

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

110

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

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Children

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.2

For a multinational trial

F.4.2.2

In the whole clinical trial

220

G. Investigator Networks to be involved in the Trial

H.4 Third Country in which the Trial was first authorised
H.4.1	Third Country in which the trial was first authorised:

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