Efficacy and Safety of LCZ696 Compared to Olmesartan in Essential Hypertensive Patients Not Responsive to Olmesartan

Study Overview
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Brief Summary
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This study will assess the efficacy and safety of LCZ696 in comparison to olmesartan in essential hypertensive patients not adequately responsive to olmesartan

Official Title
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A Randomized 8-week Double-blind, Parallel-group, Active-controlled, Multicenter Study to Evaluate Efficacy and Safety of LCZ696 200 mg in Comparison With Olmesartan 20 mg in Essential Hypertensive Patients Not Responsive to Olmesartan

Conditions
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Hypertension

Intervention / Treatment
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* Drug: LCZ696
* Drug: Olmesartan
* Drug: Placebo of LCZ696
* Drug: Placebo of Olmesartan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients with mild to moderate hypertension, untreated or currently taking antihypertensive therapy treated patients (using antihypertensive drugs within 4 weeks prior to first visit) must have an office msSBP ≥ 145 mmHg and < 180 mmHg after washout epoch and after 4 weeks run-in epoch untreated patients (either newly diagnosed or those patients with a history of hypertension but have not been taking any antihypertensive drugs for at least 4 weeks prior to first visit) must have an offcie msSBP ≥ 150 mmHg and < 180 mmHg at screening and 1 week after screening and must have an office msSBP ≥ 145 mmHg and < 180 mmHg after 4 weeks run-in epoch patients must successfully complete ABPM and pass technical requirements to be qualified for randomization Exclusion Criteria: Malignant or severe hypertension (grade 3 of WHO classification; msDBP ≥110 mmHg and/or msSBP ≥ 180 mmHg) History of angioedema, drug-related or otherwise History or evidence of a secondary form of hypertension, including but not limited to any of the following: renal parenchymal hypertension, renovascular hypertension (unilateral or bilateral renal artery stenosis), coarctation of the aorta, primary hyperaldosteronism, Cushing's disease, pheochromocytoma, polycystic kidney disease (PKD), drug-induced hypertension Patients who previously entered a LCZ696 study and had been randomized or enrolled to receive active drug treatment

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: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LCZ696 200 mg<br>Patients will be treated with one LCZ696 200 mg tablet and one placebo of olmesartan 20 mg capsule once daily for 8 weeks. | Drug: LCZ696<br> <br> Drug: Placebo of LCZ696<br> <br> |
| Active Comparator: Olmesartan 20 mg<br>Patients will be treated with one placebo of LCZ696 200 mg tablet and one olmesartan 20 mg capsule once daily for 8 weeks. | Drug: Olmesartan<br> <br> Drug: Placebo of Olmesartan<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in 24-hour Mean Ambulatory Systolic Blood Pressure (maSBP) | Twenty-four hour mean ambulatory blood pressure measurements (ABPM) will be performed at baseline and at end of study (week 8). The first 24-hour ABPM will be performed beginning at 24 hours prior to baseline visit and the second will be performed 24 hours prior to week 8 visit. | baseline, 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean 24-hour Ambulatory Diastolic Blood Pressure (maDBP) | Twenty-four hour mean ambulatory blood pressure measurements (ABPM) will be performed at baseline and at end of study (week 8). The 24-hour ABPM measurements are performed beginning 24 hours prior to baseline and week 8 visits. | baseline, 8 weeks | 
| Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) | Sitting blood pressure (BP) measurement will be taken at every visit from screening through end of study. For each participant at each visit, four separate sitting BP measurements will be obtained (with a full two minute interval between measurements) and averaged to obtain the mean | baseline, 8 weeks | 
| Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) | Sitting blood pressure (BP) measurement will be taken at every visit from screening through end of study. For each participant at each visit, four separate sitting BP measurements will be obtained (with a full two minute interval between measurements) and averaged to obtain the mean | baseline, 8 weeks | 
| Change From Baseline in Office Pulse Pressure | Mean sitting pulse pressure (msPP) will be calculated at screening through end of study at every visit. Mean sitting pulse pressure is calculated as msSBP-msDBP. | baseline, 8 weeks | 
| Number of Patients Achieving Successful Overall Blood Pressure Control | Successful overall blood pressure control is defined as both msSBP/msDBP <140/90 mmHg | 8 weeks | 
| Number of Patients Achieving Successful Mean Sitting Systolic Blood Pressure (msSBP) Control | Successful mean sitting systolic blood pressure control is defined as msSBP <140 mmHg | 8 weeks | 
| Number of Patients Achieving Successful Mean Sitting Diastolic Blood Pressure (msDBP) Control | Successful mean sitting diastolic blood pressure control is defined as msDBP <90 mmHg | 8 weeks | 
| Number of Patients Achieving Successful Mean Sitting Systolic Blood Pressure (msSBP) Response | Successful mean sitting systolic blood pressure response is defined as msSBP <140 mmHg or a reduction ≥ 20 mmHg from baseline. | baseline, 8 weeks | 
| Number of Patients Achieving Successful Mean Sitting Diastolic Blood Pressure (msDBP) Response | Successful mean sitting diastolic blood pressure response is defined as msDBP <90 mmHg or a reduction ≥10 mmHg from baseline. | baseline, 8 weeks | 
| Number of Patients With Total Adverse Events, Serious Adverse Events and Death | Number of patients with total adverse events, serious adverse events and death were reported. | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypertension,, LCZ696,, olmesartan