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

Study Overview
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Brief Summary
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This study assessed the efficacy of LCZ696 in Japanese 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 Japanese Patients With Essential Hypertension

Conditions
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Essential Hypertension

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


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 proceeding 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: 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: 20 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LCZ696 200 mg<br>LCZ696 200 mg tablet and placebo to both LCZ696 (1 tablet) and Olmesartan (1 capsule) tablet once daily for 8 weeks | Drug: LCZ696<br>* 200 mg (one tablet) or 400 mg (2 tablets of 200mg) once daily<br>Drug: Placebo<br>* Placebo to LCZ696 or Olmesartan<br>|
| Experimental: LCZ696 400 mg<br>LCZ696 200 mg tablet and a placebo to both LCZ696 (1 tablet) and Olmesartan (1 capsule) once daily for one week; then up-titrated to LCZ696 400 mg and placebo to Olmesartan (1 capsule) once daily for the remaining 7 weeks | Drug: LCZ696<br>* 200 mg (one tablet) or 400 mg (2 tablets of 200mg) once daily<br>Drug: Placebo<br>* Placebo to LCZ696 or Olmesartan<br>|
| Active Comparator: Olmesartan 20 mg<br>Olmesartan 20 mg capsule and placebo to LCZ696 (2 tablets) once daily for 8 weeks | Drug: Olmesartan<br>* Olmesartan 20 mg capsule one daily<br>Drug: Placebo<br>* Placebo to LCZ696 or Olmesartan<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) | Sitting BP measurements were performed at screening through the end of study at every visit. Four separate sitting BP were obtained with a full two-minute interval between measurements. The 4 measurements were summed and averaged, and then the baseline BP value was subtracted from the average value to get the change from baseline. | Baseline, 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean 24-hour Ambulatory SBP (maSBP) at Week 8 | Ambulatory blood pressure monitoring (ABPM) over a 24-hour period was conducted at two time-points during the study in a subset of participants. | Baseline, 8 weeks | 
| Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) | Sitting BP measurement was performed at screening through the end of study at every visit. Four separate sitting BP were obtained with a full two-minute interval between measurement. The 4 measurements were summed and averaged, and then the baseline BP value was subtracted from the average value to get the change from baseline. | Baseline, 8 weeks | 
| Percentage of Participants Achieving a Successful Response in Overall Blood Pressure Control at Week 8 | A successful response in overall BP control rate was defined as msSBP < 140 mmHg and msDBP <90 mmHg. | 8 weeks | 
| Percentage of Participants Achieving a Successful msSBP Response | Successful msSBP response was defined as < 140 mmHg or ≥ 20 mmHg reduction from baseline. | 8 weeks | 
| Percentage of Participants Achieving a Successful msDBP Response | Successfull msDBP response was defined as <90 mmHg or ≥10 mmHg reduction from baseline. | 8 weeks | 
| Change From Baseline in Mean 24-hour Ambulatory DBP (maDBP) at Week 8 | ABPM over a 24-hour period was conducted at two time-points during the study in a subset of participants. | Baseline, 8 weeks | 
| Change From Baseline in maSBP and maDBP for Daytime/Nighttime | ABPM over a 24-hour period was conducted at two time-points during the study in a subset of participants. | Baseline, 8 weeks | 
| Change From Baseline in Office Pulse Pressure | Office pulse pressure was calculated as msSBP minus msDBP. Sitting blood pressure (BP) measurement was performed at screening through the end of study at every visit. Four separate sitting BP were obtained with a full two-minute interval between measurement. The 4 measurements were summed and then averaged to calculate the mean BP value. The baseline PP value was subtracted from the week 8 PP value to determine the change from baseline in PP. | Baseline, 8 weeks | 
| Change From Baseline in Mean 24-hour Ambulatory Pulse Pressure | Ambulatory pulse pressure was calculated as hourly ambulatory SBP minus hourly ambulatory DBP in a subset of participants. | Baseline, 8 weeks | 
| Number of Patients With Adverse Events, Serious Adverse Events and Death | Participants were monitored for adverse events, serious adverse events and deaths throughout the study. | 8 weeks | 

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