Efficacy and Safety of Valsartan and Amlodipine (± HCTZ) in Adults With Moderate, Inadequately Controlled Hypertension

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of valsartan and amlodipine in fixed dose combination in adults with moderate, inadequately controlled hypertension. There was an optional study extension for eligible patients who wanted to participate that contains the triple therapy (ie, hydrochlorothiazide+ amlodipine/valsartan).

Detailed Description
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Title of study extension: An open-label, multicenter extension to evaluate the efficacy and tolerability of a 4 week therapy with hydrochlorothiazide 12.5 mg plus amlodipine 10 mg/valsartan 160 mg in hypertensive patients not adequately responding to a 4 week therapy each with the combinations of olmesartan 20 mg plus amlodipine 10 mg followed by amlodipine 10 mg/valsartan 160 mg

Official Title
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An Open-label, Multicenter Study to Evaluate the Efficacy and Tolerability of a 4 Week Therapy With the Fixed Dose Combination of Amlodipine 10 mg Plus Valsartan 160 mg in Hypertensive Patients Not Adequately Responding to a 4 Week Therapy With the Free Combination of an Angiotensin Receptor Blocker (Olmesartan 20 mg) Plus Amlodipine 10 mg

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Amlodipine
* Drug: Olmesartan medoxomil
* Drug: Amlodipine+valsartan
* Drug: Hydrochlorothiazide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for Core study: Male or female patients (>=18 years) Females must be either post-menopausal for one year, surgically sterile or using effective contraceptive methods Patients with essential hypertension (diastolic blood pressure >=100 mmHg and <110 mmHg) Inclusion Criteria for Extension: - Patients had to have a msSBP >= 140 mmHg and/or msDBP >= 90 mmHg at week 8 ie, end of core study. Exclusion Criteria for Core study: Severe hypertension (diastolic blood pressure >=110 mmHg or systolic blood pressure >= 180 mmHg) Pregnant or nursing women Treated hypertensive patients with controlled hypertension under current therapy A history of cardiovascular disease, including angina pectoris, myocardial infarction, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, transient ischemic attack, stroke, and heart failure NYHA II - IV Exclusion Criteria for Extension: prematurely discontinued the core study failed to comply with the core study protocol Other protocol-defined inclusion/exclusion criteria applied to the study.

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amlodipine(AML)+olmesartan, AML+valsartan, AML+valsartan+HCTZ<br>During the Treatment Phase 1, participants received 1 week of treatment with olmesartan 10 mg and amlodipine 5 mg once daily in free combination, followed by three weeks of treatment with olmesartan 20 mg plus amlodipine 10 mg once daily in free combination. During the treatment Phase 2 of the study participants received amlodipine 10 mg plus valsartan 160 mg for 4 weeks. During the Extension Phase, participants received 4 weeks treatment with amlodipine 10 mg plus valsartan 160 mg plus hydrochlorothiazide (HCTZ) 12.5 mg. | Drug: Amlodipine<br>* Amlodipine supplied as 5 mg tablets, taken orally once a day during Treatment Phase 1 only.<br>Drug: Olmesartan medoxomil<br>* Olmesartan medoxomil supplied as 10 mg tablets taken once a day during Treatment Phase 1 only.<br>Drug: Amlodipine+valsartan<br>* Fixed-dose combination of amlodipine 10 mg plus valsartan 160 mg tablet taken orally once a day during Treatment Phase 2 and Extension Phase.<br>* Other names: Exforge;Drug: Hydrochlorothiazide<br>* Hydrochlorothiazide (HCTZ) 12.5 mg tablets taken once a day during the Extension Phase.<br>* Other names: Sandoz;|

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) During the Core Phase of the Study | The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, systolic/diastolic blood pressure were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement. | Baseline Phase 2 (Week 4) to end of Phase 2 (Week 8) | 
| Change in Mean Sitting Diastolic Blood Pressure (msDBP) During the Extension Phase of the Study | The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, systolic/diastolic blood pressure were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement. | Baseline Phase 3 (Week 8) to end of Phase 3 (Week 12) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean Sitting Systolic Blood Pressure (msSBP) During the Core Phase of the Study | The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, systolic/diastolic blood pressure were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement. | Baseline Phase 2 (Week 4) to end of Phase 2 (Week 8) | 
| Change in Sitting Pulse Pressure During the Core Phase of the Study | Pulse pressure is systolic pressure (SP) minus diastolic pressure (DP). The arm in which the highest sitting DPs were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, SP and DP were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement. | Baseline Phase 2 (Week 4) to end of Phase 2 (Week 8) | 
| Change in Sitting Pulse Rate During the Core Phase of the Study | Pulse rate was measured once for 30 seconds just prior to blood pressure measurements in the sitting position. | Baseline Phase 2 (Week 4) to end of Phase 2 (Week 8) | 
| Percentage of Patients Who Achieved Normalized Blood Pressure During the Core Phase of the Study | Normalized Blood Pressure was defined as a msSBP < 140 mmHg and/or a msDBP < 90 mmHg. | Baseline Phase 2 (Week 4) to end of Phase 2 (Week 8) | 
| Percentage of Patients Who Achieved a Protocol-defined Blood Pressure Response During the Core Phase of the Study | Blood pressure response was defined as msSBP < 140 mmHg or a 20 mmHg decrease in msSBP at the end of Phase 2 (Week 8) compared to Baseline in Phase 2 (week 4) or a msDBP < 90 mmHg or a 10 mmHg decrease in msDBP at the end of Phase 2 compared to Baseline in Phase 2. | Baseline of Phase 2 (Week 4) to end of Phase 2 (Week 8) | 
| Change in Mean Sitting Systolic Blood Pressure (msSBP) During the Extension Phase of the Study | The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, systolic/diastolic blood pressure were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement. | Baseline Phase 3 (Week 8) to end of Phase 3 (Week 12) | 
| Change in Sitting Pulse Pressure During the Extension Phase of the Study | Pulse pressure is systolic pressure (SP) minus diastolic pressure (DP). The arm in which the highest sitting DPs were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, SP and DP were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement. | Baseline Phase 3 (Week 8) to end of Phase 3 (Week 12) | 
| Change in Sitting Pulse Rate During the Extension Phase of the Study | Pulse rate was measured once for 30 seconds just prior to blood pressure measurements in the sitting position. | Baseline Phase 3 (Week 8) to end of Phase 3 (week 12) | 
| Percentage of Patients Who Achieved Normalized Blood Pressure During the Extension Phase of the Study | Normalized Blood Pressure was defined as a msSBP < 140 mmHg and/or a msDBP < 90 mmHg. | Baseline Phase 3 (Week 8) to end of Phase 3 (Week 12) | 
| Percentage of Patients Who Achieved a Protocol-defined Blood Pressure Response During the Extension Phase of the Study | Blood pressure response was defined as msSBP < 140 mmHg or a 20 mmHg decrease in msSBP at the end of Phase 3 compared to Baseline in Phase 3 or a msDBP < 90 mmHg or a 10 mmHg decrease in msDBP at the end of Phase 3 compared to Baseline in Phase 3. | Baseline of Phase 3 (Week 8) to end of Phase 3 (Week 12) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypertension, valsartan, amlodipine