Official Title: “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 (CC) 32 mg and Hydrochlorothiazide (HCT) 25 mg Compared With CC 32 mg, HCT 25 mg and Placebo in Hypertensive Adults”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: January 2008

Intervention(s) in this Clinical Trial

• Drug: Candesartan cilexetil
  • 32 mg oral tablet
• Drug: Hydrochlorothiazide
  • 25 mg oral tablet
• Drug: Candesartan/HCT 32/25 mg

Arms, Groups and Cohorts in this Clinical Trial

• No Intervention: 4
  • Placebo
• Active Comparator: 2
  • Candesartan cilexetil
• Active Comparator: 3
  • Hydrochlorothiazide (HCT)
• Experimental: 1
  • Candesartan cilexetil + Hydrochlorothiazide Combination

Primary Measures

• Change in Sitting Diastolic Blood Pressure (DBP) From Baseline to the End of the Study (From Baseline to 8 Weeks).
  • Time Frame: 8 weeks
    Safety Issue?: No
• Change in Sitting Systolic Blood Pressure (SBP) From Baseline to the End of the Study (Baseline to 8 Weeks)
  • Time Frame: 8 weeks
    Safety Issue?: No

Secondary Measures

• The Number of Patients With Controlled Sitting DBP and Sitting SBP in Each Treatment Group at the End of the Study
  • Time Frame: 8 weeks
    Safety Issue?: No
• 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).
  • Time Frame: Baseline to 8 weeks
    Safety Issue?: No
• 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.
  • Time Frame: Baseline to 8 weeks
    Safety Issue?: No
• 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.
  • Time Frame: Baseline to 8 weeks
    Safety Issue?: No
• 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).
  • Time Frame: Baseline to 8 weeks
    Safety Issue?: No
• 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).
  • Time Frame: Baseline to 8 weeks
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 20 Years

Maximum Age for this Clinical Trial: 80 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: AstraZeneca

Overall Clinical Trial Officials and Contacts

Michael Klibaner, MD Study Director AstraZeneca  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00434967

Study ID Number: D2456C00002

ClinicalTrials.gov Identifier: NCT00434967

Health Authority: Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment

AstraZeneca Clinical Trial Information - Outside US