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

A Multi-national, Multi-center, Double-blind, Randomized, Parallel Study Comparing the Efficacy and Safety of Valsartan/Amlodipine 160/5 mg to Valsartan 160 mg Alone in Patients With Mild to Moderate Essential Hypertension Not Adequately Controlled With Valsartan 160 mg Monotherapy

This study assessed the efficacy and safety of the valsartan/amlodipine 160/5 mg single-pill combination in patients with uncomplicated essential hypertension not adequately controlled (MSDBP ≥90 mmHg and <110 mmHg) on valsartan 160 mg alone.

Study Overview

• Status: Completed
• Conditions: Essential Hypertension
• Intervention / Treatment: Drug: Valsartan 160 mg; Drug: Placebo; Drug: Valsartan/amlodipine 160/5 mg

• Study Type: Interventional
• Enrollment (Actual): 932
• Phase: Phase 3

Contacts and Locations

Study Locations

• • • Investigative site in Romainia
  • • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must give written informed consent
• Male or female ages 18 or older and less than 86 years

• Diagnosed as having essential diastolic hypertension, as follows:

  • Visit 2/Single-blind run-in entry, all participants MUST have a MSDBP ≥ 95 mmHg and < 100 mmHg
  • At Visit 3/Core double-blind treatment period entry, all patients MUST have a MSDBP >=90 mmHg and <110 mmHg

Exclusion Criteria:

• Severe hypertension
• Evidence of secondary form of hypertension (coarctation of the aorta, hyperaldosteronism, unilateral or bilateral renal artery stenosis, Cushing's disease, pheochromocytoma or polycystic kidney disease )
• Malignant hypertension
• Administration of any agent indicated for the treatment of hypertension after Visit 1
• Known moderate or malignant retinopathy.
• Known or suspected contraindications, including history of allergy or hypersensitivity to Angiotensin II Receptor Blockers (ARBs), Calcium Channel Blockers (CCBs), or to drugs with similar chemical structures
• History of hypertensive encephalopathy, cerebrovascular accident, or transient ischemic attack, myocardial infarction or all types of revascularization, angina pectoris of any type, including unstable angina
• History of heart failure Grade II-IV according to New York Heart Association (NYHA) classification
• Second of third degree heart block regardless of the use of a pacemaker, concomitant potentially life-threatening arrhythmia or symptomatic arrhythmia

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Valsartan 160 mg; One capsule Valsartan 160 mg and 1 tablet placebo to Valsartan/Amlodipine taken orally once daily at approximately 9:00 AM for 8 weeks	Drug: Valsartan 160 mg; Valsartan 160 mg capsule taken orally once daily.; Other Names: Diovan® 160mg; Drug: Placebo; 1 capsule or tablet taken orally once daily
Experimental: Valsartan/amlodipine 160/5 mg; One film-coated tablet Valsartan/amlodipine 160/5 mg and 1 capsule Placebo to Valsartan taken orally once daily at approximately 9:00 AM for 8 weeks	Drug: Placebo; 1 capsule or tablet taken orally once daily; Drug: Valsartan/amlodipine 160/5 mg; Valsartan/amlodipine 160/5mg film coated tablets taken orally once daily.; Other Names: Exforge® 160/5mg
Other: Single-Blind Run-In Valsartan 160 mg; Single-Blind Run-In treatment with one capsule Valsartan 160 mg taken orally once daily at approximately 9:00 AM for 4 weeks.	Drug: Valsartan 160 mg; Valsartan 160 mg capsule taken orally once daily.; Other Names: Diovan® 160mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Mean Sitting Diastolic Blood Pressure (MSDBP) From Baseline to Week 8 Endpoint	Three arterial blood pressure (BP) determinations were made after the participant was in the sitting position for 5 minutes according to the American Heart Association guidelines using a calibrated standard aneroid or mercury sphygmomanometer or a calibrated standard sphygmomanometer. The change in the MSDBP was calculated comparing the Week 8 readings to the readings taken at Baseline. The change from baseline in MSDBP was analyzed using an analysis of covariance model (ANCOVA) with treatment and center (pooled as appropriate) as factors and centered baseline MSDBP as a covariate.	Baseline and Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Mean Sitting Systolic Blood Pressure (MSSBP) From Baseline to Week 8 Endpoint	Three arterial blood pressure (BP) determinations were made after the participant was in the sitting position for 5 minutes according to the American Heart Association guidelines using a calibrated standard aneroid or mercury sphygmomanometer or a calibrated standard sphygmomanometer. The change in the MSSBP was calculated comparing the Week 8 readings to the readings taken at Baseline. The change from baseline in MSSBP was analyzed using an analysis of covariance model (ANCOVA) with treatment and center (pooled as appropriate) as factors and centered baseline MSSBP as a covariate	Baseline and Week 8
Percentage of Participants With a Diastolic Blood Pressure Response at 8 Week Endpoint	The percentage of participants with a Diastolic Blood Pressure Response defined as the percentage of participants with a Mean Sitting Diastolic Blood Pressure (MSDBP) < 90 mmHg or a >= 10 mmHg reduction from baseline.	Baseline and Week 8
Percentage of Participants With Diastolic Blood Pressure Control at 8 Week Endpoint	The percentage of participants with Diastolic Blood Pressure Control defined as the percentage of participants with a Mean Sitting Diastolic Blood Pressure (MSDBP) < 90 mmHg.	Week 8
Percentage of Participants With Overall Blood Pressure Control at 8 Week Endpoint	The percentage of participants with Overall Blood Pressure Control defined as the percentage of participants with a Mean Sitting Systolic Blood Pressure (MSSBP)/Mean Sitting Diastolic Blood Pressure (MSDBP) < 140/90 mmHg.	Week 8

Collaborators and Investigators

• Sponsor: Novartis

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: October 15, 2009
• First Submitted That Met QC Criteria: October 23, 2009
• First Posted (Estimate): October 26, 2009

Study Record Updates

• Last Update Posted (Estimate): May 24, 2011
• Last Update Submitted That Met QC Criteria: May 18, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Keywords: hypertension; Blood pressure; Exforge; valsartan/amlodipine
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Essential Hypertension; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Amlodipine; Valsartan
• Other Study ID Numbers: CVAA489A2317