Assessment of LCZ696 and Valsartan in Asian Patients With Salt-sensitive Hypertension

Study Overview
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Brief Summary
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This study will evaluate the effect of LCZ696 and valsartan on natriuresis, diuresis, and blood pressure in salt-sensitive Asian hypertensive patients.

Official Title
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A Randomized, Double-blind, Crossover Study to Assess the Effects of LCZ696 and Valsartan in Asian Patients With Salt-sensitive Hypertension

Conditions
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Salt-sensitive Hypertension

Intervention / Treatment
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* Drug: Valsartan
* Drug: LCZ696


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Written informed consent must be obtained before any study assessment is performed. Males and females of non-childbearing potential and of legal age (at least 18 years or older as defined by local law). Asian patients with mild to moderate essential hypertension, untreated or currently taking antihypertensive therapy with up to two drugs. Key Exclusion Criteria: Women of child-bearing potential. History of angioedema, drug-related or otherwise History of hypersensitivity to LCZ696, valsartan, or drugs of similar chemical classes. Severe hypertension (grade 3 of WHO classification; msDBP ≥100 mmHg and/or msSBP ≥ 180 mmHg) at screening or at the end of the washout period. History or evidence of a secondary form of hypertension, Transient ischemic cerebral attack (TIA) during the 12 months prior to screening or any history of stroke. History of myocardial infarction, coronary bypass surgery or percutaneous coronary intervention (PCI) during 12 month prior to screening. Current or history of hypertensive retinopathy. Previous or current diagnosis of heart failure (NYHA Class II-IV). Clinically significant valvular heart disease at screening. 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

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LCZ696 followed by Valsartan<br>Period 1: LCZ696 400mg QD for 4 weeks then washout followed by Period 2: Valsartan 320mg QD for 4 weeks | Drug: Valsartan<br>* Valsartan 320mg tablet once daily<br>Drug: LCZ696<br>* LCZ696 400mg tablet once daily<br>|
| Experimental: Valsartan followed by LCZ696<br>Period 1: Valsartan 320mg QD for 4 weeks then washout followed by Period 2: LCZ696 400mg QD for 4 weeks | Drug: Valsartan<br>* Valsartan 320mg tablet once daily<br>Drug: LCZ696<br>* LCZ696 400mg tablet once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative Sodium Excretion (Natriuresis) at Day 1 | Urine will be collected in fractions of 6 to 24 hours post-dose. From each fraction, a sample will be drawn for analysis of sodium Day 1 | 0-6 and 0-24 hours on Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative Sodium Excretion (Natriuresis) at Day 28 | Urine will be collected in fractions of 6 to 24 hours post-dose. From each fraction, a sample will be drawn for analysis of sodium Day 28 | 0-6 and 0-24 hours on Day 28 | 
| Urine Volume (Diuresis) Over Time | Urine will be collected and volume measured in fractions of 0 to 6 hours and 0 to 24 hours Day-1, Day 1 and Day 28 | Day -1, Day 1 & Day 28 | 
| Seated Office Blood Pressure (BP) (Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)) Over Time | Seated Office BP (systolic blood pressure (SBP) and diastolic blood pressure (DBP))measurements will be performed at trough(immediately prior to dosing at the clinic). Arterial BP readings will be made with an automated BP device. | Day-1, Day 14 and Day 28 | 
| Mean Sitting Pulse Pressure (PP) Over Time | Sitting mean pulse pressure rate was calculated between ambulatory SBP and DBP measurements | Day-1, Day 14 and Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypertension, salt sensitivity, valsartan, LCZ696