Antihypertensive Efficacy and Safety of Candesartan/HCT 32/25 mg in Comparison With Individual Components and Placebo

Phase 3

Completed

Interventions: Drug: Candesartan cilexetil
Drug: Hydrochlorothiazide
Drug: Candesartan/HCT 32/25 mg

Brief Summary: The aim is to compare the blood pressure lowering effect of the combination of candesartan cilexetil (candesartan) 32 mg and hydrochlorothiazide (HCT) 25 mg to that of candesartan 32 mg alone, HCT 25 mg alone and placebo in hypertensive adults.

Recruitment & Eligibility

Inclusion Criteria

Patients will be eligible for enrolment into the study (Visit 1) if they fulfil all of the following criteria:
Provision of signed Informed Consent
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.
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:
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.

Exclusion Criteria

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.
Secondary or malignant hypertension
Sitting SBP of 180 mmHg or more
Myocardial infarction, stroke, coronary bypass surgery or transient ischaemic attack within 6 months before enrolment
Angina pectoris requiring more treatment than short-acting nitrates
Chronic use of NSAIDs
Aortic or mitral valve stenosis
Cardiac failure requiring treatment
Cardiac arrhythmia requiring treatment
Gout
Renal artery stenosis or kidney transplantation
Intravascular volume depletion
Hypersensitivity to any component of the investigational products or to any sulphonamide derived drugs
Concomitant disease which may interfere with the assessment of the patient
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
Chronic liver disease
Concomitant or previous treatment with any other investigational drug within 20 days of enrolment
Previous enrolment in the present study

Arm && Interventions

Group	Intervention	Description
1	Hydrochlorothiazide	Candesartan cilexetil + Hydrochlorothiazide Combination
1	Candesartan/HCT 32/25 mg	Candesartan cilexetil + Hydrochlorothiazide Combination
1	Candesartan cilexetil	Candesartan cilexetil + Hydrochlorothiazide Combination
2	Candesartan cilexetil	Candesartan cilexetil
3	Hydrochlorothiazide	Hydrochlorothiazide (HCT)

Primary Outcome Measures

Name	Time	Method
Change in Sitting Diastolic Blood Pressure (DBP) From Baseline to the End of the Study (From Baseline to 8 Weeks).	8 weeks	Change (reduction) in sitting DBP at the end of the study, when compared to sitting DBP at baseline.
Change in Sitting Systolic Blood Pressure (SBP) From Baseline to the End of the Study (Baseline to 8 Weeks)	8 weeks	Change (reduction) in sitting SBP at the end of the study, when compared to sitting SBP at baseline.

Secondary Outcome Measures

Name	Time	Method
The Number of Patients With Controlled Sitting DBP and Sitting SBP in Each Treatment Group at the End of the Study	8 weeks	Controlled sitting SBP and sitting DBP are defined as having sitting SBP \< 140 mmHg and sitting DBP \< 90 mmHg at the end of the study
To Describe Safety and Tolerability 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.	Baseline to 8 weeks
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 Sitting DBP).	Baseline to 8 weeks
To Compare Treatment With Candesartan/HCT 32/25 mg to Each of Its Components With Regard to Change From Baseline to Week 8 in Standing DBP and Standing SBP.	Baseline to 8 weeks
To Compare Candesartan/HCT 32/25 mg to Its Components and to Placebo With Regard to Sitting DBP Control Rate at the End of the Study (Patients With Controlled Sitting DBP Are Defined as Having a Sitting DBP <90 mmHg at the End of the Study).	Baseline to 8 weeks
To Compare Candesartan/HCT 32/25 mg to Its Components and to Placebo With Regard to Sitting DBP Responder Rate (Decrease in Sitting DBP ≥10 mmHg From Baseline to the End of the Study or a Sitting DBP <90 mmHg at the End of the Study).	Baseline to 8 weeks