Efficacy and Safety of LCZ696 in Comparison to Olmesartan in Asian Patients With Essential Hypertension

Study Overview
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Brief Summary
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This study will assess the efficacy and safety of multiple doses of LCZ696 compared to olmesartan in Asian patients with essential hypertension

Official Title
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A Multi-center, Randomized, Double-blind, Active-controlled, 8-week Study to Evaluate the Efficacy and Safety of LCZ696 in Comparison to Olmesartan in Patients With Essential Hypertension

Conditions
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Essential 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 treatments within 4 weeks prior to Visit 1) must have an msSBP≥150 mmHg and <180 mmHg at the randomization visit (Visit 201) and msSBP≥140 mmHg <180 mmHg at the visit immediately preceding Visit 201 (Visit 102 or 103). Untreated patients (newly diagnosed with essential hypertension or having a history of hypertension but have not been taking any antihypertensive drugs for at least 4 weeks prior to Visit 1) must have an msSBP≥150 mmHg and <180 mmHg at both Visit 1 and Visit 201. Patients must have an absolute difference of ≤15 mmHg in msSBP between Visit 201 and the immediately preceding visit. Exclusion Criteria: Patients with severe hypertension (msDBP ≥110 mmHg and or msSBP ≥180 mmHg). History of angioedema, drug-related or otherwise, as reported by the patient. 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, and drug-induced hypertension. Patients who previously entered a LCZ696 study and had been randomized or enrolled into the active drug treatment epoch. Other protocol-defined inclusion/exclusion criteria may apply.

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 LCZ696 once daily(qd) for eight weeks along with placebo of Olmesartan 20 mg capsule once daily. | Drug: LCZ696<br>* LCZ696 200 mg tablet<br>Drug: Placebo of LCZ696<br>* Placebo tablet of LCZ696 200 mg once daily<br>Drug: Placebo of Olmesartan<br>* Placebo capsule of olmesartan 20 mg once daily<br>|
| Experimental: LCZ696 400 mg<br>Patients will start with one LCZ696 200 mg tablet and one placebo of LCZ696 once daily (qd) for one week, thereafter all patients in the treatment group will be up-titrated to two LCZ696 200 mg tablets (400 mg of LCZ696) qd for the remaining seven weeks. Placebo of Olmesartan 20 mg capsule once daily also will be taken. | Drug: LCZ696<br>* LCZ696 200 mg tablet<br>Drug: Placebo of LCZ696<br>* Placebo tablet of LCZ696 200 mg once daily<br>Drug: Placebo of Olmesartan<br>* Placebo capsule of olmesartan 20 mg once daily<br>|
| Active Comparator: Olmesartan 20 mg<br>Patients will be treated with Olmesartan 20 mg for eight weeks once daily along with placebo of LCZ696 tablets once daily. | Drug: Olmesartan<br>* Olmesartan 20 mg capsule<br>Drug: Placebo of LCZ696<br>* Placebo tablet of LCZ696 200 mg once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) Between LCZ696 200 mg Versus Olmesartan 20 mg | Sitting BP measurements will be performed at screening through end of study at every visit. Four separate sitting BP measurements will be obtained with a full two minute interval between measurements. | baseline, 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) Between LCZ696 400 mg Versus Olmesartan 20 mg | Sitting BP measurements will be performed at screening through end of study at every visit. Four separate sitting BP measurements will be obtained with a full two minute interval between measurements | baseline, 8 weeks | 
| Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) Between LCZ696 200, and LCZ696 400 mg Versus Olmesartan 20 mg | Sitting BP measurements were performed at screening through the end of the study at every study visit. A negative change from baseline indicates improvement | baseline, 8 weeks | 
| Change From Baseline in Office Pulse Pressure (msPP) | Four separate sitting BP measurements should be obtained with a full two minute interval between measurements. | baseline, 8 weeks | 
| Change From Baseline in Mean 24-hour Ambulatory Blood Pressure | In this analysis, mean 24 hour ambulatory systolic blood pressure maSBP, mean 24 hour ambulatory diastolic blood pressure maDBP, daytime and nightime maSBP and maDBP will be reported. Ambulatory blood pressure monitoring over a 24 hour period will be conducted at two time points during the study. | baseline, 8 weeks | 
| Sub-group Analysis for Change From Baseline in Mean Ambulatory Systolic Blood Pressure in Dippers. | Twenty four hour ABPM was performed twice duirng the study at baseline and week 8. The second ABPM assessment was performed only in participants who had successfully completed the ABPM assessment at baseline. Dippers were defined as participants who showed a decrease of at least 10% in maSBP during the night (10pm-6am) compared with the daytime level. A negative change from baseline indicates improvement | baseline, 8 weeks | 
| Sub-group Analysis for Change From Baseline in Mean Ambulatory Diastolic Blood Pressure in Dippers. | Twenty four hour ABPM was performed twice duirng the study at baseline and week 8. The second ABPM assessment was performed only in participants who had successfully completed the ABPM assessment at baseline. Dippers were defined as participants who showed a decrease of at least 10% in maSBP during the night (10pm-6am) compared with the daytime level. A negative change from baseline indicates improvement | baseline, 8 weeks | 
| Sub-group Analysis for Change From Baseline in Mean Ambulatory Systolic Blood Pressure in Non-dippers. | Twenty four hour ABPM was performed twice duirng the study at baseline and week 8. The second ABPM assessment was performed only in participants who had successfully completed the ABPM assessment at baseline. Dippers were defined as participants who showed a decrease of at least 10% in maSBP during the night (10pm-6am) compared with the daytime level. A negative change from baseline indicates improvement | baseline, 8 weeks | 
| Sub-group Analysis for Change From Baseline in Mean Ambulatory Diastolic Blood Pressure in Non-dippers. | Twenty four hour ABPM was performed twice duirng the study at baseline and week 8. The second ABPM assessment was performed only in participants who had successfully completed the ABPM assessment at baseline. Dippers were defined as participants who showed a decrease of at least 10% in maSBP during the night (10pm-6am) compared with the daytime level. A negative change from baseline indicates improvement | baseline, 8 weeks | 
| Number of Patients Achieving Successful Blood Pressure Control | Successful blood pressure control is defined as msSBP <140 mmHg and msDBP <90 mmHg. | 8 weeks | 
| Change From Baseline in Ambulatory Pulse Pressure | Ambulatory pulse pressure (PP) is calculated by hourly ambulatory SBP and hourly ambulatory DBP over a 24-hour period. | baseline, 8 weeks | 
| Number of Responders | Responders are patients with msSBP response (<140 mmHg or ≥20 mmHg reduction from baseline) and msDBP response (<90 mmHg or ≥10 mmHg reduction from baseline) | baseline, 8 weeks | 
| Number of Patients With Adverse Events, Serious Adverse Events, and Death as Assessment of Safety and Tolerability | Participants were monitored for adverse events, serious adverse events and deaths throughout the study. | baseline, 8 weeks | 

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