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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Essential Hypertension

Intervention / Treatment
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* Drug: Valsartan/amlodipine 160/5 mg
* Drug: Valsartan 160 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Valsartan 160 mg<br>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<br>* Valsartan 160 mg capsule taken orally once daily.<br>* Other names: Diovan® 160mg;Drug: Placebo<br>* 1 capsule or tablet taken orally once daily<br>|
| Experimental: Valsartan/amlodipine 160/5 mg<br>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: Valsartan/amlodipine 160/5 mg<br>* Valsartan/amlodipine 160/5mg film coated tablets taken orally once daily.<br>* Other names: Exforge® 160/5mg;Drug: Placebo<br>* 1 capsule or tablet taken orally once daily<br>|
| Other: Single-Blind Run-In Valsartan 160 mg<br>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<br>* Valsartan 160 mg capsule taken orally once daily.<br>* Other names: Diovan® 160mg;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Blood pressure, hypertension, Exforge, valsartan/amlodipine