A Multicenter, Multifactorial, Randomized, Double-Blind, Placebo-Controlled Dose-Finding Study of Nifedipine GITS and Candesartan in Combination Compared to Monotherapy in Adult Patients With Essential Hypertension
A Multicenter, Multifactorial, Randomized, Double-Blind, Placebo-Controlled Dose-Finding Study of Nifedipine GITS and Candesartan in Combination Compared to Monotherapy in Adult Patients With Essential Hypertension
The purpose of this study is to determine the blood pressure lowering responses of various dose combinations of nifedipine GITS and candesartan as compared to treatment with each component on their own (monotherapy) and placebo (a look-alike tablet without active ingredient). The drugs - nifedipine GITS and candesartan - which are being investigated are currently approved for use in patients with essential hypertension alone or together with other antihypertensive drugs (combination therapy), but the optimal dose of nifedipine GITS and candesartan used together in the treatment of essential hypertension has not been established yet. In this study patients will be treated with various doses of nifedipine GITS and/or candesartan or placebo. These different regimens will be administered once a day and will be assessed based on their blood pressure lowering effects (mean sitting diastolic blood pressure) in subjects with mild to moderate essential hypertension.
Inclusion Criteria:
Exclusion Criteria:
Severe hypertension (Grade 3 WHO classification; MSDBP ≥110 mmHg and/or MSSBP ≥ 180 mmHg)
Inability to washout of antihypertensive drugs (even if prescribed for another indication) safely for a period of 14 weeks.
History of hypertensive retinopathy - known Keith-Wagener Grade III or IV
History of hypertensive encephalopathy
Cerebrovascular ischemic event (stroke, transient ischemic attack [TIA])within the previous 12 months
History of intracerebral hemorrhage or subarachnoid hemorrhage
Evidence of secondary hypertension such as coarchation of the aorta, pheochromocytoms, hypersaldosteronism, etc.
Type I diabetes mellitus (DM) or poorly controlled DM Type II as evidenced by a glycosylated hemoglobin [HbA1C] of greater than 9% on visit 1.
Allergies or known intolerance to one of the investigational drugs/drug class or to one of their ingredients
Any history of heart failure, New York Heart Association (NYHA) classification III or IV
Severe coronary heart disease as manifest by a history of myocardial infarction or unstable angina in the last 6 months prior to visit 1.
Clinically significant cardiac valvular disease
History of malignancy in the last 5 years, excluding basal or skin cancer
Uncorrected hypokalemia or hyperkalemia: potassium outside 3.0-5.0 mmol/L
Surgical or medical conditions that might alter the metabolism, excretion or distribution or absorption of any drug
Investigation trial participation with receipt of investigational study drug within the last month
Previous assignment to treatment in this study
Female subjects who are pregnant or lactating.
Subjects who have night employment (night shift).
Subjects with an aortic aneurysm that, in the opinion of the investigator, will be unsuitable to be enrolled in the study.
Thought by the investigator for any reason to be unsuitable for participation in a clinical study
Systemic use of known cytochrome P450-3A4 inhibitors (e.g cimetidine, anti-human immunodeficiency virus [HIV] protease inhibitors e.g. ritonavir, azole anti-mycotics eg. ketoconazole,) or inducers (e.g rifampicin, anti-epileptic drugs eg. phenytoin, carbamazepine and phenobarbitone) or some P450-3A4 substrates (e.g quinidine, digoxin, tacrolimus)
Present severe rhythm or conduction disorder:
Atrial fibrillation
Second or third degree heart block without a pacemaker.
Baseline QTc >450 msec
History of non-compliance, alcoholism or drug abuse that in the opinion of the investigator will compromise successful completion of the study.
If differences greater than 20 mmHg for SBP and 10 mmHg for DBP are present on 3 consecutive BP readings, the subject should be excluded from the study.
Petoria, Gauteng, South Africa
Chungchungbuk-do, 361-711, South Korea
Hostalets de Balenyà, Barcelona 08550, Spain