Resumen

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.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Male and female subjects 18 years or older. Female subjects must be either post-menopausal for one year, surgically sterile, or using an effective contraceptive method. Hormonal contraceptive use is disallowed.
Subjects must have mild to moderate essential hypertension (Grade 1 and 2 WHO classifications) as measured by calibrated standard sphygmomanometer. (MSDBP of ≥90 mmHg and \< 110 mmHg at Visit 1 (placebo run-in), and MSDBP of ≥95 mmHg and \< 110 mmHg at visit 2 (randomization)
Subjects must have an absolute difference in their MSDBP of less than 10 mmHg between Visit 1 (placebo run- in) and Visit 2 (randomization).

Criterios de exclusión

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
Gastrointestinal disease or surgery resulting in the potential for malabsorption
Severe gastrointestinal tract narrowing; kock pouch (ileostomy after proctocolectomy)
Cholestasis or biliary obstruction or history of pancreatic injury or clinical significant increase of lipase, amylase, or bilirubin.
Liver disease or AST/ALT levels \>3 x ULN
Renal insufficiency, defined as eGFR of \< 50 mL/min (computed using the Cockroft-Gault formula), or on hemodialysis
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.

Intervenciones

drug

Candesartan cilexetil (Atacand), 4 mg

4 mg of candesartan as capsule

drug

Candesartan cilexetil (Atacand), 8 mg

8 mg candesartan as capsule

drug

Nifedipine GITS (Adalat, BAYA1040), 20 mg

20 mg nifedipine as tablet

drug

Nifedipine GITS (Adalat, BAYA1040), 30 mg

30 mg nifedipine as tablet

drug

Nifedipine GITS (Adalat, BAYA1040), 60 mg

60 mg nifedipine as tablet

drug

Placebo

3 different placebo tablets corresponding nifedipine doses and 1 placebo capsule corresponding to candesartan doses

drug

Candesartan cilexetil (Atacand), 16 mg

16 mg of candesartan as capsule

drug

Candesartan cilexetil (Atacand), 32 mg

32 mg of candesartan as capsule

Ubicaciones

Bahía Blanca, Buenos Aires, Argentina

Quilmes, Buenos Aires, Argentina

Zárate, Buenos Aires, Argentina

Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina

Corrientes, Corrientes Province, Argentina

Córdoba, Córdoba Province, Argentina

Rosario, Santa Fe Province, Argentina

Santa Fe, Santa Fe Province, Argentina

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

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Candesartan cilexetil (Atacand), 4 mg

Candesartan cilexetil (Atacand), 8 mg

Nifedipine GITS (Adalat, BAYA1040), 20 mg

Nifedipine GITS (Adalat, BAYA1040), 30 mg

Nifedipine GITS (Adalat, BAYA1040), 60 mg

Placebo

Candesartan cilexetil (Atacand), 16 mg

Candesartan cilexetil (Atacand), 32 mg

Ubicaciones

Patrocinadores