Clinical Trials Register

Summary
EudraCT Number:	2007-004938-16
Sponsor's Protocol Code Number:	00-MEP-04
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2008-04-18
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

2007-004938-16

A.3

Full title of the trial

A RANDOMISED, DOUBLE-BLIND STUDY TO COMPARE THE EFFECT ON SYMPATHETIC ACTIVITY AND HEMODYNAMIC PROFILE OF BARNIDIPINE AND AMLODIPINE IN PATIENTS WITH MILD TO MODERATE ESSENTIAL HYPERTENSION.

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

00-MEP-04

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	Astellas Pharma Europe B.V.
B.1.3.4	Country	Netherlands
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	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	Amlopin
D.2.1.1.2	Name of the Marketing Authorisation holder	LEK S.A. - ul. Podlipie 16 - 95-010 Stryko'w - Poland
D.2.1.2	Country which granted the Marketing Authorisation	Poland
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	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	AMLODIPINE
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	5
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	Yes
D.3.11.13.1	Other medicinal product type	Non Applicabile
D.IMP: 2
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	LIBRADIN*28CPS 10MG R.M.
D.2.1.1.2	Name of the Marketing Authorisation holder	SIGMATAU IND.FARM.RIUNITE 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	Modified-release capsule, hard
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	Barnidipine
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)	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	Yes
D.3.11.13.1	Other medicinal product type	Non Applicabile

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	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	Modified-release capsule, hard
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 hypertension

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	10015488
E.1.2	Term	Essential hypertension

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 compare the effect of barnidipine and amlodipine on sympathetic activity by assessment of plasma norepinephrine levels in the forearm after 12 weeks of therapy.

E.2.2

Secondary objectives of the trial

To investigate tolerability (safety) and anti-hypertensive activity (efficacy) of barnidipine and amlodipine after 12 weeks of therapy. To compare the effect of barnidipine and amlodipine on sympathetic activity by assessing the net norepinephrine balance in the forearm after 12 weeks of therapy in responding* subjects. To compare the effect of barnidipine and amlodipine on forearm norepinephrine spill over after 12 weeks therapy in the first 12 responding subjects. To compare the effect of barnidipine and amlodipine on forearm blood flow and vascular resistance (plethysmography) after 12 weeks of therapy in responding subjects. * SiDBP<90 mmHg and SiSBP<140 mmHg at week 12

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Written informed consent has been obtained.
2. A diagnosis of mild to moderate essential hypertension has been made at visit 1 in a non-hospitalised patient. For the diagnosis of mild to moderate hypertension the JNC VI guidelines and the following updates are valid: Subjects presenting a systolic blood pressure of 140 –179 mmHg inclusive and/or a diastolic blood pressure of 90 – 109 mmHg inclusive and who are not taking antihypertensive medication.
3. Male or female, aged 18 to 75 years inclusive at the time of the first study visit.
4. Previous treatment for hypertension took place or no anti-hypertensive treatment was in place prior to the study. ''Previously treated'' is defined as having received anti-hypertensive therapy within the last 14 days. ''Previously treated'' subjects must be able to tolerate a maximum 21 day drug free period.

E.4

Principal exclusion criteria

1. A history of uncomplicated myocardial infarction within six months prior to the study is reported.
2. Any history of myocardial infarction (M.I.) complicated by congestive heart failure or post M.I. angina is reported.
3. A primary, haemodynamically cardiac valve disease (e.g. aortic stenosis, aortic insufficiency, mitral insufficiency and mitral stenosis) is diagnosed.
4. Any history of either cerebrovascular accident, including transient ischaemic attack (TIA) and reversible neurological deficit (RIND) or hypertensive encephalopathy is reported.
5. An unstable angina pectoris is diagnosed.
6. Any other clinically relevant cardiovascular disease is reported including:
moderate to severe heart failure (NYHA class III or IV)
peripheral vascular disease
hypertensive retinopathy Keith-Wagener grade III or IV
all tachycardias requiring drug treatment
7. Sustained ventricular arrhythmias, atrial fibrillation, bradycardia (<=50 bpm), second degree or complete AV block is reported.
8. A renal insufficiency defined as serum creatinine above 150 μmol/l is diagnosed.
9. Serum liver enzyme concentrations above three times the upper limit of normal are observed. 10. Diabetes mellitus with poor glucose control or complicated by clinically important retinopathy, peripheral neuropathy or autonomic nephropathy is diagnosed. 11. A history of primary aldosteronism, haematological or autoimmune disease is reported. 12.Untreated hyperthyroidism or hyperthyroidism treated with beta-adrenergic blocking drugs is diagnosed/reported.
13. A history of gastro-intestinal surgery which could interfere with the drug absorption is reported.
14. A history of malignancy including leukaemia and lymphoma within the past five years (skin cancer other than melanoma is an exception) is reported.
15. Use of drugs known to affect blood pressure (such as tricyclic anti-depressants, carbenoxolone, phenothiazines, some common cold medications and amphetamines) after the first dose of single-blind placebo medication is reported/detected.
16. A history of drug, medication or alcohol abuse is known.
17. Hypersensitivity or intolerance to either barnidipine or amlodipine or to other calcium antagonists is known. 18. An investigational drug within 28 days prior to the first dose of single-blind medication was taken.
19. Participation in a previous barnidipine study.
20. Any forbidden concomitant medication as listed in appendix 1 of this protocol including ketoconazole and erythromycin, was used.
21. Participation in any clinical trial within 3 months, or participation in more than 3 clinical trials within 12 months, prior to the expected date of enrolment into the study took place.
22. Women of child-bearing potential who are pregnant or intend to become pregnant during the study or who are sexually active and practising an unreliable method of birth control or will be lactating during the study. Reliable contraceptive methods are intra-uterine devices, contraceptive pills of combination type plus barrier method, hormonal implants and injectable contraceptives.
23. An allergy to barnidipine, amlodipine or to any other calcium antagonist or any of their components is known.
24. A clinical condition which, in the opinion of the investigator, would not allow safe completion of the protocol is observed.

E.5 End points

E.5.1

Primary end point(s)

Forearm plasma norepinephrine levels at baseline and after 12 weeks of therapy as measured after CPT.

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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

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)

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

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

E.8.2.3

Other

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

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

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

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 2008-04-18.	Yes
F.3.3.2	Women of child-bearing potential using contraception	Information not present in EudraCT
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	60

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

2008-02-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2006-07-06

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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