Efficacy/Safety of Valsartan Plus Amlodipine and Amlodipine Alone in Patients With Hypertension

Inclusion criteria

• Male or female outpatients ≥ 18 years and 5 mIU/ml).
• Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precluded intercourse with a male partner and women whose partners had been sterilized by vasectomy or other means, UNLESS they met the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels > 40 mIU/m or 6 weeks post-surgical bilateral oophorectomy with or without hysterectomy OR were using one or more of the following acceptable methods of contraception: surgical sterilization (e.g., bilateral tubal ligation, vasectomy), and double-barrier methods (any double combination of: intra-uterine device [IUD], male or female condom with spermicidal gel, diaphragm, sponge, cervical cap). Acceptable methods of contraception included total abstinence at the discretion of the investigator in cases where the age, career, lifestyle, or sexual orientation of the patient ensured compliance. Reliable contraception had to be maintained throughout the study and for 7 days after study drug discontinuation. Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal were not acceptable methods of contraception. Hormonal contraceptive use was disallowed.
• History of heart failure Grade II-IV according to the New York Heart Association (NYHA) classification.
• Second or third degree heart block with or without a pacemaker.
• Concomitant potentially life threatening arrhythmia or symptomatic arrhythmia.
• Angina pectoris of any type, including unstable angina pectoris.
• Clinically significant valvular heart disease.
• Evidence of a secondary form of hypertension, including but not limited to any of the following: coarctation of the aorta, hyperaldosteronism, unilateral or bilateral renal artery stenosis, Cushing disease, pheochromocytoma, polycystic kidney disease.
• Known moderate or malignant retinopathy, defined as: moderate (retinal signs of hemorrhage, microaneurysm, cotton-wool spot, hard exudates, or a combination thereof) or malignancy (signs of moderate retinopathy plus swelling of the optic disk).
• Evidence of hepatic disease as determined by any one of the following: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values greater than two times the upper limit of normal at Visit 1, a history of hepatic encephalopathy, a history of esophageal varices, or a history of a portocaval shunt.
• Evidence of renal impairment as determined by anyone of the following: serum creatinine > 1.5 times the upper limit of normal at Visit 1, a history of dialysis, or a history of nephrotic syndrome.
• History of clinically significant allergies including asthma, and/or multiple drug allergies.
• Any surgical or medical condition with the potential to significantly alter the absorption, distribution, metabolism, or excretion of any drug including but not limited to any of the following: history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, bowel resection, gastric bypass, gastric stapling, or gastric banding, currently active or active inflammatory bowel syndrome within 12 months prior to Visit 1, currently active gastritis, ulcers, or gastrointestinal/rectal bleeding, or urinary tract obstruction regarded as clinically meaningful by the investigator.
• Any surgical or medical condition, which in the opinion of the investigator or the Novartis monitor, placed the patient at higher risk from his/her participation in the study, or were likely to prevent the patient from complying with the requirement of the study or completing the trial period.
• Volume depletion based on the investigator's clinical judgment using vital signs, skin turgor, moistness of mucous membranes, and laboratory values.
• Any ch