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

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01681576

Enrollment

Registered

2012-09-10

Start date

2012-08-31

Completion date

2013-10-31

Last updated

2015-11-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Salt-sensitive Hypertension

Keywords

hypertension, salt sensitivity, valsartan, LCZ696

Brief summary

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

Interventions

DRUGValsartan

Valsartan 320mg tablet once daily

DRUGLCZ696

LCZ696 400mg tablet once daily

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

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/

Design outcomes

Primary

Measure	Time frame	Description
Cumulative Sodium Excretion (Natriuresis) at Day 1	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

Measure	Time frame	Description
Cumulative Sodium Excretion (Natriuresis) at Day 28	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	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	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	Day-1, Day 14 and Day 28	Sitting mean pulse pressure rate was calculated between ambulatory SBP and DBP measurements

Countries

Hong Kong, Singapore, South Korea, Taiwan, United States

Participant flow

Recruitment details

Period 1: 4 weeks treatment with LCZ696 400mg QD or Valsartan 320mg, 1-2 weeks wash-out, followed by period 2, 4 weeks treatment with Valsartan 320mg QD or LCZ696 400mg QD

Participants by arm

Arm	Count
LCZ696 Followed by Valsartan Period 1: LCZ696 400mg QD for 4 weeks then washout followed by Period 2: Valsartan 320mg QD for 4 weeks	36
Valsartan 320mg Period 1: 4 weeks treatment with Valsartan 320mg QD, 1-2 weeks wash-out, followed by period 2, 4 weeks treatment with LCZ696 400mg QD	36
Total	72

Withdrawals & dropouts

Period	Reason	FG000	FG001
Period 1	Adverse Event	1	0
Period 1	Protocol Deviation	1	0
Period 2	Non-compliance with study treatment	1	0
Period 2	subject/guardian decision	3	1

Baseline characteristics

Characteristic	LCZ696 Followed by Valsartan	Valsartan 320mg	Total
Age, Continuous	55.7 years STANDARD_DEVIATION 12.5	58.9 years STANDARD_DEVIATION 7.5	57.3 years STANDARD_DEVIATION 10.3
Sex: Female, Male Female	13 Participants	13 Participants	26 Participants
Sex: Female, Male Male	23 Participants	23 Participants	46 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	15 / 71	15 / 67
serious Total, serious adverse events	0 / 71	0 / 67

Outcome results

Primary

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

Time frame: 0-6 and 0-24 hours on Day 1