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

A Double-blind, Randomized, Multicenter, Parallel Group Study to Evaluate the Efficacy, Tolerability, and Safety of Treatment With the Combination of Valsartan/Amlodipine 160/5 mg Compared to Amlodipine 10 mg in Patients With Essential Hypertension Not Adequately Controlled With Amlodipine 5 mg Alone

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.

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