ICH GCP - EU Clinical trials Registry

Summary
EudraCT Number:	2012-002606-40
Sponsor's Protocol Code Number:	CLCZ696B2207
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-09-17
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

A. Protocol Information

A.1

Member State Concerned

Netherlands - Competent Authority

A.2

EudraCT number

2012-002606-40

A.3

Full title of the trial

A randomized, double-blind, parallel group study to evaluate metabolic effects of LCZ696 and amlodipine in obese hypertensive subjects

A.3.1

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

Evaluation of the metabolic effects of LCZ696 and amlodipine in obese hypertensive subjects

A.4.1

Sponsor's protocol code number

CLCZ696B2207

A.7

Trial is part of a Paediatric Investigation Plan

No

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Novartis Pharma Service 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 B.V.
B.5.2	Functional name of contact point	CRA
B.5.3	Address:
B.5.3.1	Street Address	Raapopseweg 1
B.5.3.2	Town/ city	Arnhem
B.5.3.3	Post code	6824 DP
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+31(0)263782340

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	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	not available
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	400
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	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 Hexal
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	AMLODIPINE
D.3.9.1	CAS number	88150-42-9
D.3.9.4	EV Substance Code	SUB05467MIG
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	10
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

Mild to moderate essential hypertension in obese subjects

E.1.1.1

Medical condition in easily understood language

High blood pressure in obese patients

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	15.0
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

No

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the effect of LCZ696 400 mg QD as compared to amlodipine 10 mg QD on insulin sensitivity after 8 weeks of treatment in obese hypertensive subjects.

E.2.2

Secondary objectives of the trial

• To evaluate the effect of LCZ696 and amlodipine on subcutaneous adipose tissue lipolysis at rest and the oxydative metabolism at rest
• To evaluate the tolerability of LCZ696 and amlodipine in obese hypertensive subjects.

E.2.3

Trial contains a sub-study

No

E.3

Principal inclusion criteria

• Written informed consent must be obtained before any study assessment is performed.
• Males and females of non-childbearing potential ≥ 18 years of age.
• Subjects with mild to moderate essential hypertension,
• Untreated subjects must have a mean seated SBP (msSBP) ≥ 130 mmHg and < 180 mmHg at screening.
• Pre-treated subjects must have a msSBP ≤ 160 mmHg at screening and < 180 mmHg at the end of the washout period.
• Waist circumference ≥ 102 cm (men) and ≥ 88 cm (women).

E.4

Principal exclusion criteria

• Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer; or longer if required by local regulations.
• Women of child-bearing potential.
• Pregnant or nursing (lactation) women.
• History of angioedema, drug-related or otherwise.
• History of hypersensitivity to LCZ696, amlodipine, or drugs of similar chemical classes.
• Severe hypertension (grade 3 of WHO classification; msDBP ≥100 mmHg and/or msSBP ≥ 180 mmHg) at screening or at the end of the washout period.
• Type 1 or Type 2 diabetes mellitus.
• Dyslipidemia requiring pharmacological therapy with a fibrate or nicotinic acid.
• Concomitant use of anti-hypertensives, anti-diabetics, or drug with effects on glucose or lipid metabolism for the duration of the study.

E.5 End points

E.5.1

Primary end point(s)

Difference in insulin sensitivity index after treatment with LCZ696 or amlodipine.

E.5.1.1

Timepoint(s) of evaluation of this end point

8 weeks

E.5.2

Secondary end point(s)

• Subcutaneous adipose tissue lipolysis at rest.
• Oxidative metabolism at rest.
• Number of patients with abnormal laboratory values, vital signs, ECGs.

E.5.2.1

Timepoint(s) of evaluation of this end point

8 weeks

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

No

E.6.2

Prophylaxis

No

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

No

E.6.9

Dose response

No

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

No

E.6.12

Pharmacoeconomic

No

E.6.13

Others

No

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

No

E.7.1.1

First administration to humans

No

E.7.1.2

Bioequivalence study

No

E.7.1.3

Other

No

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

No

E.7.4

Therapeutic use (Phase IV)

No

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

No

E.8.1.3

Single blind

No

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

No

E.8.1.7

Other

No

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

No

E.8.2.3

Other

No

E.8.2.4

Number of treatment arms in the trial

2

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

No

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

3

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

No

E.8.6.2

Trial being conducted completely outside of the EEA

No

E.8.7

Trial has a data monitoring committee

No

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.8.9.1

In the Member State concerned years

0

E.8.9.1

In the Member State concerned months

9

E.8.9.1

In the Member State concerned days

0

E.8.9.2

In all countries concerned by the trial years

0

E.8.9.2

In all countries concerned by the trial months

9

E.8.9.2

In all countries concerned by the trial days

0

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.1.2.1

Number of subjects for this age range:

90

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

10

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

No

F.3.3.1

Women of childbearing potential not using contraception

No

F.3.3.2

Women of child-bearing potential using contraception

No

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

40

F.4.2

For a multinational trial

F.4.2.1

In the EEA

100

F.4.2.2

In the whole clinical trial

100

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

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

N.

Competent Authority Decision

Authorised

N.

Date of Competent Authority Decision

2012-09-17

N.

Ethics Committee Opinion of the trial application

Favourable

N.

Ethics Committee Opinion: Reason(s) for unfavourable opinion

N.

Date of Ethics Committee Opinion

2012-09-28

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-07-29

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