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

Novartis

Status and phase: Completed; Phase 3

Conditions: Essential Hypertension

Treatments: Drug: placebo; Drug: Amlodipine 5 mg capsules; Drug: Valsartan 160 mg capsules

Study type: Interventional

Funder types: Industry

Identifiers

NCT00437645

CVAA489A2404

Details and patient eligibility

About

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.

Enrollment: 1,183 patients

Sex: All

Ages: 55+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,183 participants in 2 patient groups

Valsartan/amlodipine 160/5 mg

Experimental group

Description:

Twelve (12) weeks treatment with the combination of valsartan/amlodipine 160/5 mg. Together with the active medication, patients received a placebo that matched amlodipine 5 mg. The three capsules were taken by mouth with water once daily in the morning, regardless of meals. Patients were instructed not to take their study medication the morning of their study visits. Instead, they brought the study medication with them to the site and took it there as instructed by the investigator.

Treatment:

Drug: Valsartan 160 mg capsules

Drug: placebo

Drug: Amlodipine 5 mg capsules

Amlodipine 10 mg

Active Comparator group

Description:

Eight (8) weeks of treatment with amlodipine 10 mg (two 5 mg capsules). Together with the active medication, the patients received a placebo that matched valsartan 160 mg. At Week 8, patients were switched and treated with the combination of valsartan/amlodipine 160/5 mg and a placebo that matched amlodipine 5 mg for an additional 4 weeks until the end of the study. The three capsules were taken by mouth with water once daily in the morning, regardless of meals. Patients were instructed not to take their study medication the morning of their study visits. Instead, they brought the study medication with them to the site and took it there as instructed by the investigator.

Treatment:

Drug: Valsartan 160 mg capsules

Drug: placebo

Drug: Amlodipine 5 mg capsules