Efficacy and Safety of LCZ696A in Patients With Essential Hypertension

Study Overview
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Brief Summary
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This study was a dose-ranging efficiacy study in patients with essential hypertension to assess the blood pressure lowering effect, and safety of LCZ696 compared to valsartan and placebo. The study will also evaluate the efficacy and safety of AHU377 as compared to placebo.

Official Title
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A Multi-center, Randomized, Double-blind, Placebo and Active Controlled, Parallel Group, Dose Range Study to Evaluate the Efficacy and Safety of LCZ696 Comparatively to Valsartan, and to Evaluate AHU377 to Placebo After 8 Week Treatment in Patients With Essential Hypertension

Conditions
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Hypertension

Intervention / Treatment
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* Drug: LCZ696
* Drug: Valsartan
* Drug: AHU377
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or females from 18 up to and including 75 years Patients with mild-to-moderate uncomplicated essential hypertension, untreated or currently taking antihypertensive therapy (monotherapy or combination therapy of 2 drugs; therapy with a fixed dose combination of two active substances represents 2 drugs) Untreated patients must have had an office msDBP≥ 95 mmHg at the randomization visit (Visit 3) and the 2 preceding visits (Visits 1 and 2). Treated patients must have had an office msDBP≥ 90 mmHG after washout (Visit 2), and a msDBP> 95 mmHg at baseline (Visit 3); Exclusion Criteria: Severe hypertension (msSBP ≥180 mmHg and/or msDBP ≥110 mmHg) History of angioedema, drug-related or otherwise, as reported by the patient Type 1 or Type 2 diabetes mellitus (according to the ADA criteria) History or evidence of a secondary form of hypertension, such as renal parenchymal hypertension, renovascular hypertension, coarctation of the aorta, primary hyperaldosteronism, Cushing's disease, drug-induced hypertension, unilateral or bilateral renal artery stenosis, pheochromocytoma, polycystic kidney disease, etc. History of angina pectoris, myocardial infarction, coronary bypass surgery, ischemic heart disease, surgical or percutaneous arterial intervention of any kind (coronary, carotid or peripheral intervention), stroke, TIA (transient ischemic attack), carotid artery stenosis, aortic aneurysm or peripheral arterial disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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 100 mg<br>Participants received LCZ696 100 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily. | Drug: LCZ696<br> <br> Drug: Placebo<br> <br> |
| Experimental: LCZ696 200 mg<br>Participants received LCZ696 200 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily. | Drug: LCZ696<br> <br> Drug: Placebo<br> <br> |
| Experimental: LCZ696 400 mg<br>Participants received LCZ696 400 mg (200 mg LCZ696 for one week and then up-titration to 400 mg LCZ696 for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily. | Drug: LCZ696<br> <br> Drug: Placebo<br> <br> |
| Active Comparator: Valsartan 80 mg<br>Participants received Valsartan 80 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily. | Drug: Valsartan<br> <br> Drug: Placebo<br> <br> |
| Active Comparator: Valsartan 160 mg<br>Participants received Valsartan 160 mg and matching placebo to LCZ696, Valsatan and AHU377 (5 tablets and 2 capsules) daily. | Drug: Valsartan<br> <br> Drug: Placebo<br> <br> |
| Active Comparator: Valsartan 320 mg<br>Participants received Valsartan 320 mg (160 mg valsartan capsules for one week followed by 320 mg valsartan capsules for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily. | Drug: Valsartan<br> <br> Drug: Placebo<br> <br> |
| Experimental: AHU377 200 mg<br>Participants received AHU377 200 mg and matching placebo to LCZ696 and Valsartan (5 tablets and 2 capsules) daily. | Drug: AHU377<br> <br> Drug: Placebo<br> <br> |
| Placebo Comparator: Placebo<br>Participants received matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily. | Drug: Placebo<br> <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 Diastolic Blood Pressure (msDBP) | 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, week 8 | 

Secondary 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 the study at every study visit. | baseline, week 8 | 
| Change From Baseline in 24-hour Mean Ambulatory DBP (maDBP) and maSBP | Hourly mean ambulatory DBP and SBP post-dosing was calculated for each post-dosing hour over 24 hours by taking the average of the readings taken in the corresponding post-dosing hour at randomization and at week 8. | baseline, 8 weeks | 
| Change From Baseline in Daytime maDBP and maSBP | Hourly mean ambulatory DBP and SBP post-dosing was calculated for each post-dosing hour over 24 hours by taking the avergae of the readings taken in the corresponding post-dosing hour at randomization and at week 8. Daytime mean SBP and DBP were the averages of the hourly means between 6 am and 10 pm. | baseline, 8 weeks | 
| Change From Baseline in Nighttime maDBP and maSBP | Hourly mean ambulatory DBP and SBP post-dosing was calculated for each post-dosing hour over 24 hours by taking the average of the readings taken in the corresponding post-dosing hour at randomization and at week 8. Nighttime mean SBP and DBP were the averages of the hourly means between 10 pm and 6 am. | baseline, 8 weeks | 
| Percentage of Participants Who Achieved a Successful Response in msDBP | Successful response in msDBP is defined as msDBP <90 mmHg or a reduction ≥ 10 mmHg from baseline. | 8 weeks | 
| Percentage of Participants Who Achieved a Successful Response in msSBP | Successful response in msSBP is defined as msSBP <140 mmHg or a reduction ≥ 20 mmHg from baseline. | 8 weeks | 
| Percentage of Participants Who Achieved Successful Control in msDBP | Successful control in msDBP is defined as msDBP <90 mmHg. | 8 weeks | 
| Percentage of Participants Who Achieved Successful Control in msSBP | Successful control in msSBP is defined as <140 mmHg. | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension, valsartan, LCZ696