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

Overview

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

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

Study Type

• Study Type: Interventional
• Study Design
  • Allocation: Randomized
  • Intervention Model: Crossover Assignment
  • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Study Primary Completion Date: October 2013

Interventions

• Drug: Valsartan
  • Valsartan 320mg tablet once daily
• Drug: LCZ696
  • LCZ696 400mg tablet once daily

Arms, Groups and Cohorts

• Experimental: LCZ696 followed by Valsartan
  • Period 1: LCZ696 400mg QD for 4 weeks then washout followed by Period 2: Valsartan 320mg QD for 4 weeks
• Experimental: Valsartan followed by LCZ696
  • Period 1: Valsartan 320mg QD for 4 weeks then washout followed by Period 2: LCZ696 400mg QD for 4 weeks

Clinical Trial Outcome Measures

Primary Measures

• Cumulative Sodium Excretion (Natriuresis) at Day 1
  • Time Frame: 0-6 and 0-24 hours on 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

Secondary Measures

• Cumulative Sodium Excretion (Natriuresis) at Day 28
  • Time Frame: 0-6 and 0-24 hours on 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
• Urine Volume (Diuresis) Over Time
  • Time Frame: Day -1, Day 1 & Day 28
  • 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
• Seated Office Blood Pressure (BP) (Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)) Over Time
  • Time Frame: Day-1, Day 14 and Day 28
  • 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.
• Mean Sitting Pulse Pressure (PP) Over Time
  • Time Frame: Day-1, Day 14 and Day 28
  • Sitting mean pulse pressure rate was calculated between ambulatory SBP and DBP measurements

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • Novartis Pharmaceuticals
• Provider of Information About this Clinical Study
  • Sponsor
• Overall Official(s)
  • Novartis Pharmaceuticals, Study Director, Novartis Pharmaceuticals