Efficacy and Safety of Valsartan/Amlodipine Compared to Amlodipine in Patients With Essential Hypertension

This study was designed to compare the efficacy, tolerability, and safety of the combination valsartan/amlodipine 160/5 mg versus amlodipine 10 mg in patients with essential hypertension not adequately controlled (defined as mean sitting systolic blood pressure \[msSBP\] ≥ 130 mmHg and ≤ 160 mmHg) on amlodipine 5 mg alone. The study evaluated both the efficacy and tolerability of the treatments by providing data that assessed blood pressure and the proportion of patients developing peripheral edema.


Eligibility Criteria:
Inclusion Criteria:

* Male or female outpatients ≥ 55 years of age
* Patients with essential hypertension measured using a validated automated oscillometric device at Visit 1
* Non-treated patients must have a MSSBP ≥ 140 mmHg and ≤ 160 mmHg
* Patients pre-treated on monotherapy prior to Visit 1 must have MSSBP ≤ 160 mmHg
* To be eligible for randomization at Visit 2 (Day 1) all patients must have a MSSBP ≥ 130 mmHg and ≤ 160 mmHg
* No peripheral edema at Visit 2 (randomization)
* Written informed consent to participate in this study prior to any study procedures

Exclusion Criteria:

* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant
* Known or suspected contraindications, including history of allergy or hypersensitivity to angiotensin receptor blockers, calcium channel blockers, or to drugs with similar chemical structures
* Patients taking more than 1 antihypertensive medication at Visit 1
* Administration of any agent indicated for the treatment of hypertension after Visit 1 with the exception of pre-treated patients that require tapering down of anti-hypertensive treatments. For patients with previous antihypertensive medication that require a gradual downward titration, the tapering down should be done according to manufacturers instructions and last dose should be taken by week -2 prior to randomization
* msSBP \> 180 mmHg or msDBP \> 110 mmHg at any time between Visit 1 and Visit 2
* 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's disease, polycystic kidney disease, or pheochromocytoma
* History of hypertensive encephalopathy, cerebrovascular accident, transient ischemic attack, myocardial infarction, percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG) 12 months prior to Visit 1
* History of heart failure Grade II - IV according to the NYHA classification
* Second or third degree heart block with or without a pacemaker
* Concomitant potentially life threatening arrhythmia or symptomatic arrhythmia
* Concomitant unstable angina pectoris
* Clinically significant valvular heart disease
* Patients with Type 1 diabetes mellitus
* Patients with Type 2 diabetes mellitus who are not well controlled based on the investigator's judgment. It is recommended that Type 2 diabetic patients are adequately controlled and, if treated with medication, be on a stable dose of oral anti-diabetic medication for at least 4 weeks prior to Visit 1
* Evidence of hepatic disease as determined by one of the following: AST or ALT values \> 2x UNL at study entry, a history of hepatic encephalopathy, history of esophageal varices, or history of portocaval shunt
* Evidence of renal impairment as determined by one of the following: serum creatinine \> 1.5 x UNL at visit 1, history of dialysis, or history of nephrotic syndrome
* Serum potassium values \> 5.5 mmol/L at study entry
* Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug
* Any surgical or medical condition which, at the discretion of the investigator or Novartis medical monitor, places the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study period
* Volume depletion based on the investigator's clinical judgment using vital signs, skin turgor, moistness of mucous membranes, and laboratory values
* Any severe, life-threatening disease within the past five years
* History of drug or alcohol abuse within the last 2 years
* Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer
* Inability to communicate and comply with all study requirements including the unwillingness or inability to provide informed consent
* Persons directly involved in the execution of this protocol