Efficacy and Safety of LCZ696 200 mg + Amlodipine 5 mg in Comparison With Amlodipine 5 mg in Hypertensive Patients Not Responding to Amlodipine

Study Overview
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Brief Summary
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This study will assess whether LCZ696 when used in combination with amlodipine will provide greater BP lowering benefit compared to amlodipine alone in Asian hypertensive patients not adequately responsive to amlodipine therapy.

Official Title
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A Randomized, 8-week, Double-blind, Parallel-group, Active-controlled, Multicenter Study to Evaluate the Efficacy and Safety of the Combination of LCZ696 200 mg + Amlodipine 5 mg in Comparison With Amlodipine 5 mg in Patients With Essential Hypertension Not Adequately Responsive to Amlodipine 5 mg Monotherapy Treatment

Conditions
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Essential Hypertension

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must give written informed consent and have a diagnosis of hypertension: Untreated patients must have an msSBP ≥ 150 mmHg and < 180 mmHg at both Visit 1 and Visit 101. Pre-treated patients must have an msSBP ≥ 145 mmHg and < 180 mmHg after wash out at Visit 101. All patients must have an office msSBP ≥ 145 mmHg and < 180 mmHg at the completion of the 4-week run-in epoch (at the randomization visit (Visit 201). Patients must successfully complete ABPM and pass technical requirements at Visit 201. 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. Transient ischemic cerebral attack (TIA) during the 12 months prior to Visit 1 or any history of stroke. History of myocardial infarction, coronary bypass surgery or PCI during the 12 months prior to Visit 1 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LCZ696 and amlodipine<br>Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (had an office msSBP ≥145 mmHg and <180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks. | Drug: LCZ696<br>* LCZ696 will use tablets available at a strength of 200mg. Patients will be instructed to take the prescribed medication once a day.<br>Drug: Amlodipine<br>* Amlodipine will use tablets available at a strength of 5 mg. Patients will be instructed to take the prescribed medication once a day.<br>|
| Active Comparator: Amlodipine<br>Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (had an office msSBP ≥145 mmHg and <180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks. | Drug: Amlodipine<br>* Amlodipine will use tablets available at a strength of 5 mg. Patients will be instructed to take the prescribed medication once a day.<br>Drug: Placebo<br>* Matching placebo to LCZ696<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Systolic Blood Pressure (maSBP) | The change in mean 24 hour ambulatory systolic blood pressure (maSBP) from baseline to end of the study (week 8) in the 2 groups was measured. A greater reduction from baseline in the LCZ696 group indicates a positive treatment effect. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean 24-hour ABPM Diastolic Blood Pressure (maDBP) | The change in mean 24 hour maDBP from baseline to end of the study was measured. A reduction from baseline indicates a positive treatment effect. | 8 weeks | 
| Change in Mean Sitting Systolic Blood Pressure (msSBP) | The change in the patient's msSBP from baseline to end of the study was measured. A reduction from baseline indicates a positive treatment effect. | 8 weeks | 
| Change in Mean Sitting Diastolic Blood Pressure (msDBP) | The change in the patient's msDBP from baseline to end of the study was measured. A reduction from baseline indicates a positive treatment effect. | 8 weeks | 
| Change in Sitting Pulse Pressure (PP) | The change in the patient's mean sitting PP from baseline to end of the study was measured. Pulse pressure measures the difference in mean sitting systolic blood pressure and mean sitting diastolic blood pressure. | 8 weeks | 
| Number of Participants Achieving Systolic and Diastolic Blood Pressure Control (< 140/90 mmHg) | The number of participants achieving a systolic and diastolic blood pressure < 140/90 mmHg was measured. This outcome measure shows how well a given blood pressure treatment can achieve a given blood pressure target or goal. Participants who achieved the target blood pressure were determined based on the mean SBP and DBP measurements taken at the end of the study. If the participants' BP measurement was below the above target, they were considered to have successful blood pressure control. | 8 weeks | 
| Number of Participants Achieving Successful Response in msSBP (< 140 mmHg or a Reduction ≥ 20 mmHg From Baseline) | The number of participants who achieved successful treatment response in the msSBP of < 140mmHg or a reduction ≥ 20 mmHg from baseline after completing study treatment was measured. Participants who achieved either of the above targets were deemed as a having a successful response. | 8 weeks | 
| Number of Participants Achieving Successful Response in msDBP (< 90 mmHg or a Reduction ≥ 10 mmHg From Baseline) | The number of participants who achieved successful treatment response in msDBP of < 90mmHg or a reduction ≥ 10mmHg from baseline after completing study treatment was measured. Participants who achieved either of the above targets were deemed as having a successful response. | 8 weeks of treatment | 
| Number of Participants With Adverse Event | Participants were monitored for adverse events, serious adverse events and death. | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Essential hypertension, High blood pressure