Study of Nifedipine GITS and Candesartan Combination Compared to Monotherapy in Patients With Essential Hypertension

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
• •1. Gastrointestinal disease or surgery resulting in the potential for malabsorption
• •2. Severe gastrointestinal tract narrowing; kock pouch (ileostomy after proctocolectomy)
• •3. Cholestasis or biliary obstruction or history of pancreatic injury or clinical significant increase of lipase, amylase, or bilirubin.
• •4. Liver disease or AST/ALT levels \>3 x ULN
• •5. 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.