Antihypertensive Efficacy and Safety of Candesartan/HCT 32/12.5 and 32/25 mg in Comparison With Candesartan 32 mg

Condition(s) targeted: Hypertension

Intervention: Candesartan cilexetil (Drug); Hydrochlorothiazide (Drug); Hydrochlorothiazide (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: AstraZeneca

Official(s) and/or principal investigator(s):
Established Brands HTN/CHF Medical Sience Director, MD, Study Director, Affiliation: AstraZeneca
Gerd Bonner, MD, Principal Investigator, Affiliation: MEDIAN Kliniken Bad Krozingen

In this study it is intended to compare the blood pressure lowering effect of the combination of candesartan cilexetil (candesartan) 32 mg and hydrochlorothiazide (HCT) 25 mg and the combination of candesartan 32 mg and HCT 12. 5 mg to that of candesartan 32 mg alone in patients whose blood pressure is not well controlled on candesartan 32 mg monotherapy. The Primary Objectives are to compare sitting BP lowering effect of candesartan/HCT 32/25 mg and candesartan/HCT 32/12. 5 mg with that of candesartan 32 mg, respectively.

Official title: A Double Blind, Randomised, 3-Arm Parallel Group, Multicentre, 8-Week, Phase III Study to Assess Antihypertensive Efficacy and Safety of the Combination of Candesartan Cilexetil (CC) /HCT 32/12.5mg and 32/25mg vs. CC 32mg Alone in Patients With Inadequate BP Control on Monotherapy With CC 32mg

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

Primary outcome: Change (reduction) in sitting BP (24 hours after dose)

Secondary outcome:

Proportion of patients with controlled sitting BP in each treatment group

Occurrence of Adverse Events and discontinuation of study medication due to AEs from baseline (randomisation) to the end of the study

Minimum age: 20 Years. Maximum age: 80 Years. Gender(s): Both.

Criteria:

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,

which the patient and the physician are willing to withdraw at enrolment and change to candesartan monotherapy

- Mean sitting DBP 90-114 mmHg

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

criterion:

- Mean sitting DBP 90-114 mmHg on treatment with candesartan 32 mg monotherapy (after 2

weeks with candesartan 16 mg and 6 weeks with candesartan 32 mg monotherapy). The run-in period should not be shorter than 8 weeks.

Exclusion Criteria:

- Involvement in the planning and conduct of the study (applies to both AstraZeneca

staff, CRO staff or staff at the investigational centre)

- Pregnant or lactating women, or women of childbearing potential not practising an

adequate method of contraception eg, intrauterine device, oral contraception or progesterone implant and verified by a negative pregnancy test at Visit 1

- Secondary or malignant hypertension

- Sitting SBP of 180 mmHg or more

- Patients who are treated with candesartan 16 mg in combination with a diuretic or with

candesartan 32 mg with or without any additional antihypertensive treatment

- 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

- 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

- Chronic liver disease or known liver enzyme values above three times the upper limit

of the reference range for S-ASAT or S-ALAT

- Concomitant or previous treatment with other investigational drugs within 20 days of

enrolment

- Previous enrolment in the present study

- S-creatinine of 180 μmol/l or above for men and of 140 μmol/l or above for women

- S-sodium or S-potassium outside the reference range

- Less than 85% compliance with study medication during the run-in phase

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AstraZeneca Information - Outside of the US

Starting date: September 2006
Ending date: October 2007
Last updated: March 19, 2008