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

Essential Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00437645
• Other study ID #: CVAA489A2404
• Status: Completed
• Phase: Phase 3
• First received: February 16, 2007
• Last updated: November 3, 2014
• Start date: January 2007
• Est. completion date: November 2007

Study information

• Verified date: November 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationFinland: Finnish Medicines AgencyArgentina: Ministry of HealthChile: Instituto de Salud Pública de ChileEcuador: Public Health MinistryGermany: BfArMNorway: Norwegian Medicines AgencySpain: Spanish Agency of MedicinesSpain: Ministry of Health and ConsumptionSweden: Medical Products AgencySwitzerland: SwissmedicTurkey: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1183
• Est. completion date: November 2007
• Est. primary completion date: November 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 55 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Essential Hypertension
• Hypertension

Intervention

Drug:
• Valsartan 160 mg capsules

• Amlodipine 5 mg capsules

• placebo
capsules

Locations

Country	Name	City	State
Argentina	sites in Argentina	Agentina
Chile	sites in Chile	Chile
Ecuador	sites in Ecuador	Ecuador
Finland	sites in Finland	Finland
France	sites in France	France
Germany	sites in Germany	Germany
Italy	sites in Italy	Italy
Norway	sites in Norway	Norway
Spain	sites in Spain	Spain
Sweden	sites in Sweden	Sweden
Switzerland	sites in Switzerland	Switzerland
Turkey	sites in Turkey	Turkey

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Argentina,  Chile,  Ecuador,  Finland,  France,  Germany,  Italy,  Norway,  Spain,  Sweden,  Switzerland,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to Week 8	Blood pressure (BP) was measured at trough (24±3 hours post-dose). The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. If there was < 0. 5 mmHg difference in BP between the 2 arms, the non-dominant arm was used. At each visit, after the patient was in a sitting position with the back supported and both feet placed on the floor for 5 minutes, systolic and diastolic BP were measured 3 times with an automated BP monitor and appropriate size cuff. Means of the 3 measurements were calculated. A negative change indicates lowered BP.	Baseline to Week 8	No
Primary	Percentage of Patients With Peripheral Edema From Baseline to Week 8	Only occurrences of peripheral edema quantified as a reported adverse event coded as peripheral edema were included in the analysis. If a patient experienced more than one occurrence of peripheral edema between Day 1 and Week 8, it was only counted once in the analysis.	Baseline to Week 8	Yes
Secondary	Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to Week 8	Blood pressure (BP) was measured at trough (24±3 hours post-dose). The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. If there was < 0. 5 mmHg difference in BP between the 2 arms, the non-dominant arm was used. At each visit, after the patient was in a sitting position with the back supported and both feet placed on the floor for 5 minutes, systolic and diastolic BP were measured 3 times with an automated BP monitor and appropriate size cuff. Means of the 3 measurements were calculated. A negative change indicates lowered BP.	Baseline to Week 8	No
Secondary	Change in Mean Sitting Systolic and Diastolic Blood Pressure (msSBP, msDBP) From Baseline to Weeks 4, 8, and 12	Blood pressure (BP) was measured at trough (24±3 hours post-dose). The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. If there was < 0. 5 mmHg difference in BP between the 2 arms, the non-dominant arm was used. At each visit, after the patient was in a sitting position with the back supported and both feet placed on the floor for 5 minutes, systolic and diastolic BP were measured 3 times with an automated BP monitor and appropriate size cuff. Means of the 3 measurements were calculated. A negative change indicates lowered BP.	Baseline to Weeks 4, 8, and 12	No
Secondary	Percentage of Patients Achieving a Systolic Response at Weeks 4, 8, and 12	Systolic response was defined as msSBP < 130 mmHg or at least a 20 mmHg reduction from baseline in msSBP at Weeks 4, 8, and 12. Blood pressure (BP) was measured at trough (24±3 hours post-dose). The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. At each visit, after the patient was in a sitting position with the back supported and both feet placed on the floor for 5 minutes, systolic and diastolic BP were measured 3 times with an automated BP monitor and appropriate size cuff. Means of the 3 measurements were calculated.	Baseline to Weeks 4, 8, and 12	No