Clinical Trials Register

Summary
EudraCT Number:	2006-003963-30
Sponsor's Protocol Code Number:	D2456C00002
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2006-11-23
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

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2006-003963-30

A.3

Full title of the trial

A Double-blind, Randomised, 4-arm Parallel Group, Multicentre, 8-week, Phase III Study to Assess the Antihypertensive Efficacy and Safety of the Combination of Candesartan Cilexetil 32 mg and Hydrochlorothiazide 25 mg in Comparison with Candesartan Cilexetil 32 mg, Hydrochlorothiazide 25 mg and Placebo in Hypertensive Adults.

A.4.1

Sponsor's protocol code number

D2456C00002

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	AstraZeneca AB
B.1.3.4	Country	Sweden
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	Atacand Plus
D.2.1.1.2	Name of the Marketing Authorisation holder	AstraZeneca Kft, Magyarorszag
D.2.1.2	Country which granted the Marketing Authorisation	Hungary
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	Candesartan cilexetil/hydrochlorothiazide 16/12.5 mg
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	Candesartan cilexetil
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	16
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Hydrochlorothiazide
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	12.5
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	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	Atacand
D.2.1.1.2	Name of the Marketing Authorisation holder	AstraZeneca Kft, Magyarorszag
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	Atacand 32 mg
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	Candesartan cilexetil
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	32
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.IMP: 3
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	No
D.2.1.1.1	Trade name	Hydrochlorothiazide
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	Hydrochlorothiazide 12.5 mg
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	Hydrochlorothiazide
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	12.5
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	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	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
D.8 Placebo: 3
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

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9
E.1.2	Level	LLT
E.1.2	Classification code	10020772

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

1.To compare sitting DBP lowering effect of candesartan cilexetil (candesartan)/hydrochlorothiazide (HCT) 32/25 mg with that of candesartan 32 mg.
2. To compare sitting Systolic Blood Pressure (SBP) lowering effect of candesartan /HCT 32/25 mg with that of candesartan 32 mg.
3. To compare sitting DBP lowering effect of candesartan/HCT 32/25 mg with that of HCT 25 mg.
4. To compare sitting SBP lowering effect of candesartan/HCT 32/25 mg with that of HCT 25 mg.

E.2.2

Secondary objectives of the trial

··To compare candesartan/HCT 32/25 mg and each of its components to placebo with regard to change in sitting blood pressures.
·To compare candesartan/HCT 32/25 mg to its components and to placebo with regard to hypertension control rate at the end of the study (patients with controlled sitting SBP and DBP are defined as having SBP <140 mmHg and DBP <90 mmHg at the end of the study).
·To describe safety of the study treatments with regard to adverse events including those that lead to treatment discontinuation as well as with regard to pulse rate, laboratory, electrocardiographic and physical examination findings.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients will be eligible for the study if they fulfil all of the following criteria:

1. Provision of signed Informed Consent.
2. Male or female aged 20-80 years.
3. Primary hypertension, untreated or treated with a maximum of 2 antihypertensive
drugs (substances), which the patient and the physician are willing to withdraw at
enrolment and replace with placebo.
4. Mean sitting DBP 90-114 mmHg (value calculated in the eCRF) at Visits 1 and 2.

Patients will be eligible for randomisation (Visit 4) if they fulfil the following criterion:

5. Mean sitting DBP of 90-114 mmHg (value calculated in the eCRF) at the end of the
4-week single-blind placebo run-in period. The run-in period should not be shorter
than 4 weeks.

E.4

Principal exclusion criteria

Patients will be excluded from the study if they fulfil any of the following criteria:

1. Involvement in the planning and conduct of the study (applies to both AstraZeneca
staff, Contract Research Organisation staff or staff at the investigational centre).
2. Pregnant or lactating women, or women of childbearing potential not practising an
adequate method of contraception eg, intrauterine device, oral contraception or
progesterone implant. Pregnancy must be excluded by a negative pregnancy test at
Visit 1.
3. Secondary or malignant hypertension.
4. Sitting SBP of 180 mmHg or more.
5. Myocardial infarction, stroke, coronary bypass surgery or transient ischaemic attack within 6 months before enrolment.
6. Angina pectoris requiring more treatment than short-acting nitrates.
7. Chronic use of NSAIDs.
8. Aortic or mitral valve stenosis.
9. Cardiac failure requiring treatment.
10. Cardiac arrhythmia requiring treatment.
11. Gout.
12. Renal artery stenosis or kidney transplantation.
13. Intravascular volume depletion.
14. Hypersensitivity to any component of the investigational products or to any
sulphonamide derived drugs.
15. Concomitant disease which may interfere with the assessment of the patient.
16. Past or present alcohol or drug abuse, or any condition associated with poor
compliance that in the opinion of the investigator might affect the patient’s
participation in the study.
17. Chronic liver disease.
18. Concomitant or previous treatment with any other investigational drug within 20
days of enrolment.
19. Previous enrolment in the present study.

Patients will be excluded at Visit 2 if they fulfil any of the following criteria:

20. Liver enzyme values above three times the upper limit of the central laboratory’s
reference range for S-ASAT or S-ALAT (based on sample taken at Visit 1).
21. S-creatinine of 180 μmol/l or above for men and of 140 μmol/l or above for women (based on sample taken at Visit 1).
22. S-sodium, S-potassium or S-calcium outside the reference range of the central
laboratory (based on sample taken at Visit 1).

Patients will be excluded from randomisation (Visit 4) if they fulfil the following criteria:

23. Positive pregnancy test
24. Less than 85% compliance with study medication during the run-in phase between Visit 2 and Visit 4.

(Sitting DBP 90 – 114 mmHg criterion should also be fulfilled, see Section 3.3.2, Inclusion criteria, No. 5)

E.5 End points

E.5.1

Primary end point(s)

Change in sitting DBP (24 hours after dose) from baseline (randomisation) to the end of the study (8 weeks).
Change in sitting SBP (24 hours after dose) from baseline (randomisation) to the end of the study (8 weeks)

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

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.8.2.3.1

Comparator description

Candesartan Cilexetil and Hydrochlorothiazide

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

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

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
F.1.1.1	In Utero	Information not present in EudraCT
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	Information not present in EudraCT
F.1.1.3	Newborns (0-27 days)	Information not present in EudraCT
F.1.1.4	Infants and toddlers (28 days-23 months)	Information not present in EudraCT
F.1.1.5	Children (2-11years)	Information not present in EudraCT
F.1.1.6	Adolescents (12-17 years)	Information not present in EudraCT
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 2006-11-23.	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	220
F.4.2	For a multinational trial
F.4.2.1	In the EEA	1206
F.4.2.2	In the whole clinical trial	2000

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

2007-04-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2007-02-07

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2008-02-04

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