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| ID | Type | Description | Link |
|---|---|---|---|
| 2013-001643-30 | EudraCT Number |
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To evaluate the blood pressure lowering effect and safety of LCZ696 when given alone and in combination with amlodipine in patients with essential hypertension.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LCZ696 200 mg | Experimental | Patients randomized to this treatment arm will receive LCZ696 200 mg once daily for 8 weeks. |
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| LCZ696 400 mg | Experimental | Patients randomized to this treatment arm will receive LCZ696 400 mg once daily for 8 weeks. |
|
| Amlodipine 5 mg | Active Comparator | Patients randomized to this treatment arm will receive amlodipine 5 mg once daily for 8 weeks. |
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| Amlodipine 10 mg | Active Comparator | Patients randomized to this treatment arm will receive amlodipine 10 mg once daily for 8 weeks. |
|
| LCZ696 200 mg and amlodipine 5 mg | Experimental | Patients randomized to this treatment arm will receive LCZ696 200 mg and amlodipine 5 mg once daily for 8 weeks. |
|
| LCZ696 200 mg and amlodipine 10 mg |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LCZ696 | Drug | Experimental monotherapy doses |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline in mean sitting systolic blood pressure (msSBP) of LCZ696 monotherapy compared to placebo | Sitting blood pressure will be measured at trough (immediately prior to dosing at clinic) and recorded at all study visits. At the first study visit, blood pressure will be measured in both arms and the arm with highest sitting SBP will be found and used for all subsequent readings throughout the study. The 4 repeat sitting measurements will be made at 2 minute intervals and the mean of these four sitting systolic blood pressure measurements will be used as the mean sitting systolic blood pressure for that visit. | baseline, 8 weeks |
| Change from baseline in mean sitting systolic blood pressure (msSBP) of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone. | Sitting blood pressure will be measured at trough (immediately prior to dosing at clinic) and recorded at all study visits. The 4 repeat sitting measurements will be made at 2 minute intervals and the mean of these four sitting systolic blood pressure measurements will be used as the mean sitting systolic blood pressure for that visit. | baseline, 8 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline in mean sitting Diastolic Blood Pressure (msDBP) of LCZ696 monotherapy compared to placebo | Sitting blood pressure will be measured at trough (immediately prior to dosing at clinic) and recorded at all study visits. The 4 repeat sitting measurements will be made at 2 minute intervals and the mean of these four sitting diastolic blood pressure measurements will be used as the mean sitting diastolic blood pressure for that visit. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
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| ID | Term |
|---|---|
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| C549068 | sacubitril and valsartan sodium hydrate drug combination |
| D017311 | Amlodipine |
| ID | Term |
|---|---|
| D004095 | Dihydropyridines |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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Patients randomized to this treatment arm will receive LCZ696 200 mg and amlodipine 5 mg once daily for 1 week followed by LCZ696 200 mg and amlodipine 10 mg once daily for 7 weeks. |
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| LCZ696 400 mg and amlodipine 5 mg | Experimental | Patients randomized to this treatment arm will receive LCZ696 200 mg and amlodipine 5 mg once daily for 1 week followed by LCZ696 400 mg and amlodipine 5 mg once daily for 7 weeks. |
|
| LCZ696 400 mg and amlodipine 10 mg | Experimental | Patients randomized to this treatment arm will receive LCZ696 200 mg and amlodipine 5 mg once daily for 1 week followed by LCZ696 400 mg and amlodipine 10 mg once daily for 7 weeks. |
|
| Placebo | Placebo Comparator | Patients randomized to this treatment arm will receive placebo once daily for 8 weeks. |
|
| Amlodipine |
| Drug |
Active comparator monotherapy doses |
|
| LCZ696 and amlodipine combination | Drug | Experimental combination doses |
|
| Placebo | Drug | Placebo comparator dose |
|
| baseline, 8 weeks |
| Change from baseline in mean sitting Diastolic Blood Pressure of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone | Sitting blood pressure will be measured at trough (immediately prior to dosing at clinic) and recorded at all study visits. The 4 repeat sitting measurements will be made at 2 minute intervals and the mean of these four sitting diastolic blood pressure measurements will be used as the mean sitting diastolic blood pressure for that visit. | baseline, 8 weeks |
| Change from baseline in pulse pressure | Pulse pressure will be calculated as the difference between msSBP and msDBP for both office BP and ABPM. | baseline, 8 weeks |
| Change from baseline in mean 24-hour ambulatory Systolic Blood Pressure of LCZ696 monotherapy compared to placebo | The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours. | baseline, 8 weeks |
| Change from baseline in mean 24-hour ambulatory Diastolic Blood Pressure of LCZ696 monotherapy compared to placebo | The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours. | baseline, 8 weeks |
| Change from baseline in mean daytime ( > 6am and ≤ 10 pm) ambulatory Systolic Blood Pressure of LCZ696 monotherapy compared to placebo | The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours. | baseline, 8 weeks |
| Change from baseline in mean daytime ( > 6am and ≤ 10 pm) ambulatory Diastolic Blood Pressure of LCZ696 monotherapy compared to placebo | The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours. | baseline, 8 weeks |
| Change from baseline in mean nighttime (> 10 pm and ≤ 6 am) ambulatory Systolic Blood Pressure of LCZ696 monotherapy compared to placebo | The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours. | baseline, 8 weeks |
| Change from baseline in mean nighttime (> 10 pm and ≤ 6 am) ambulatory Diastolic Blood Pressure of LCZ696 monotherapy compared to placebo | The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours. | baseline, 8 weeks |
| Change from baseline in trough to peak ratio of mean 24-hour ambulatory Systolic Blood Pressure of LCZ696 monotherapy compared to placebo | The trough to peak ratio of mean 24-hour ambulatory Systolic Blood Pressure will be calculated using the systolic blood pressure effects at trough (post-dosing hour 24) compared to the maximum systolic blood pressure effect found in the hours after dosing. | baseline, 8 weeks |
| Change from baseline in trough to peak ratio of mean 24-hour ambulatory Diastolic Blood Pressure of LCZ696 monotherapy compared to placebo | The trough to peak ratio of mean 24-hour ambulatory Diastolic Blood Pressure will be calculated using the diastolic blood pressure effects at trough (post-dosing hour 24) compared to the maximum diastolic blood pressure effect found in the hours after dosing. | baseline, 8 weeks |
| Change from baseline in mean 24-hour ambulatory Systolic Blood Pressure of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone | The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours. | baseline, 8 weeks |
| Change from baseline in mean 24-hour ambulatory Diastolic Blood Pressure of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone | The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours. | baseline, 8 weeks |
| Change from baseline in mean daytime ( > 6am and ≤ 10 pm) ambulatory Systolic Blood Pressure of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone | The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours. | baseline, 8 weeks |
| Change from baseline in mean daytime ( > 6am and ≤ 10 pm) ambulatory Diastolic Blood Pressure of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone | The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours. | baseline, 8 weeks |
| Change from baseline in mean nighttime (> 10 pm and ≤ 6 am) ambulatory Systolic Blood Pressure of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone | The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours. | baseline, 8 weeks |
| Change from baseline in mean nighttime (> 10 pm and ≤ 6 am) ambulatory Diastolic Blood Pressure of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone | The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours. | baseline, 8 weeks |
| Percentage of patients achieving msSBP <140 mmHg and msDBP <90 mmHg | The percentage of patients achieving blood pressure control (msSBP <140 mmHg and msDBP <90 mmHg) after 8 weeks of treatment will be calculated. | 8 weeks |
| Percentage of patients achieving msSBP <140 mmHg or a reduction ≥20 mmHg from baseline | The percentage of patients achieving a successful response in msSBP (msSBP <140 mmHg or a reduction ≥20 mmHg from baseline) after 8 weeks of treatment will be calculated. | Baseline, 8 weeks |
| Percentage of patients achieving msDBP <90 mmHg or a reduction ≥10 mmHg from baseline | The percentage of patients achieving a successful response in msSBP (msDBP <90 mmHg or a reduction ≥10 mmHg from baseline) after 8 weeks of treatment will be calculated. | Baseline, 8 weeks |
| Number of patients reporting adverse events | As an assessment of safety of monotherapy and combination therapy of LCZ696, total adverse events, serious adverse events and deaths after 8 weeks of treatment will be reported . | 8 weeks |