Sodium Excretion of LCZ696 in Patients With Hypertension; Heart Failure and Healthy Volunteers

A Randomized, Double-blind, Controlled, Crossover Study to Evaluate the Sodium Excretion of LCZ696 in Patients With Stable Heart Failure, in Patients With Hypertension, and in Healthy Volunteers

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01353508

Enrollment

Registered

2011-05-13

Start date

2011-03-31

Completion date

2012-08-31

Last updated

2015-11-23

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

Conditions

Hypertension

Keywords

Sodium excretion,, LCZ696

Brief summary

Assess mechanism of action of LCZ696 related to sodium excretion.

Interventions

DRUGLCZ696

200 mg and 400 mg tablets

DRUGValsartan

160 mg tablets

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Patients with heart failure: documented NYHA class II-III heart failure * Patients with hypertension: stable hypertensive medication for the preceding 2 months

Exclusion criteria

* Women of childbearing potential * History of recent myocardial infarction * History of dialysis or renal transplant * Patients with type 1 diabetes mellitus

Design outcomes

Primary

Measure	Time frame	Description
24-hour Urinary Sodium Excretion	day 1	Urine was collected in 12-hour intervals, and of each pooled 24-hour (daily) sample, sodium concentration was measured. The measure type used for this outcome measure (OM) was Geometric Least square Means (LSM).
Cumulative 7-day Urinary Sodium Excretion	7 day-cummulative (days 1 through 7)	Urine was collected in 12-hour intervals, and of each pooled 24-hour (daily) sample, sodium concentration was measured. The measure type used for this outcome measure (OM) was Geometric Least square Means (LSM).

Secondary

Measure	Time frame	Description
7-day Cumulative Diuresis	7-day cumulative (days 1 through 7)	Urine was collected in 12-hour intervals, and of each pooled 24-hour (daily) sample, urine volume was measured. The measure type used for this OM was Geometric LSM.
Urinary Cyclic Guanosine Monophosphate (cGMP) Excretion Over 24 Hours	day 1, day 6, day 7	cGMP was analyzed at a central laboratory. The measure type used for this OM was Geometric LSM.
Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	2, 4, 6 and 12 hours post dose on day 1; 24 hours post dose on day 2; 2, 4, 6 and 12 hours post dose on day 7	MR-proANP was analyzed at a central laboratory.
Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	0.5, 1, 2, 4, 6 and 12 hours post dose on day 1; 24 hours post dose on day 2; 0, 4, 6 and 12 hours post dose on day 7	BNP was analyzed at a central laboratory.
Percent Change From Baseline in Mid-regional Pro-adrenomedullin (MR-proADM) Biomarker	2, 4, 6 and 12 hours post dose on day 1; 24 hours post dose on day 2; 0, 4, 6 and 12 hours post dose on day 7	MR-proADM was analyzed at a central laboratory.
Percent Change From Baseline in C-terminal-proendothelin-1 (CT-proET-1) Biomarker	12 hours post dose on day 1; 24 hours post dose on day 2; 0 and 12 hours post dose on day 7	CT-proET-1 was analyzed at a central laboratory.
Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	2, 4, 6 and 12 hours post dose on day 1; 24 hours post dose on day 2; 0, 4, 6 and 12 hours post dose on day 7	NT-proBNP was analyzed at a central laboratory.
Percent Change From Baseline in C-type Natriuretic Peptide (proCNP) Biomarker	2, 4, 6, 8 and 12 hours post dose on day 1; day 2; 0, 4, 6, 8 and 12 hours post dose on day 7	ProCNP was analyzed at a central laboratory.
Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	2, 4, 6 and 12 hours post dose on day 1; 24 hours post dose on day 2; 0, 4, 6 and 12 hours post dose on day 7	Urine was collected in 12-hour intervals, and of each pooled 24-hour (daily) sample, sodium, potassium, albumin and calcium were measured.
Percent Change From Baseline in Blood Plasma Creatinine	4, 6 and 12 hours post dose on day 1; 24 hours post dose on day 2; 0, 4, 6 and 12 hours post dose on day 7	Blood plasma creatinine was analyzed at a central laboratory.
Glomerular Filtration Rate (GFR) Over Time	0, 2, 4 and 6 hours post dose on day 1; 0, 2, 4 and 6 hours post dose on day 7	GFR was used as a measure of renal function.
Renal Blood Flow (RBF) Over Time	0, 2, 4 and 6 hours post dose on day 1; 0, 2, 4 and 6 hours post dose on day 7	RBF was used as a measure of renal function.
Supine Systolic Blood Pressure	0, 0.5, 1, 2, 4, 8 and 12 hours post dose on day 1; day 2; 0, 0.5, 1, 2, 4, 8 and 12 hours post dose on day 7	Systolic blood pressure measurements were taken.
Supine Diastolic Blood Pressure	0, 0.5, 1, 2, 4, 8 and 12 hours post dose on day 1; day 2; 0, 0.5, 1, 2, 4, 8 and 12 hours post dose on day 7	Diastolic blood pressure measurements were taken.
Supine Pulse Rate	0, 0.5, 1, 2, 4, 8 and 12 hours post dose on day 1; day 2; 0, 0.5, 1, 2, 4, 8 and 12 hours post dose on day 7	Pulse rate measurements were taken.
Percent Change From Baseline in Aldosterone Biomarker	6 and 12 hours post dose on day 1; 24 hours post dose on day 2; 0, 6 and 12 hours post dose on day 7	Aldosterone was analyzed at a central laboratory.
24-hour Diuresis	day 1	Urine was collected in 12-hour intervals, and of each pooled 24-hour (daily) sample, urine volume was measured. The measure type used for this OM was Geometric LSM.

Countries

Russia

Participant flow

Recruitment details

In each of the HF and HTN cohorts, 16 participants (total = 32) received LCZ696 or Valsartan in period 1. Then, there was a cross-over where participants received LCZ96 or Valsartan in period 2.

Participants by arm

Arm	Count
LCZ696 to Valsartan - Heart Failure (HF) Cohort Participants in this arm received Valsartan 160 mg twice daily (bid) during open-label run-in, LCZ696 200 mg bid double blind treatment during period 1, Valsartan 160 mg bid during wash-out, and Valsartan 160 mg bid double blind treatment during period 2.	8
Valsartan to LCZ696 - HF Cohort Participants in this arm received Valsartan 160 mg twice daily bid during open-label run-in, Valsartan 160 mg bid during period 1, Valsartan 160 mg bid during wash-out, and LCZ696 200 mg bid double blind treatment during period 2.	8
LCZ696 to Valsartan - Hypertension (HTN) Cohort Participants in this arm received Valsartan 320 mg once daily (qd) during open-label run-in, LCZ696 400 mg qd double blind treatment during period 1, Valsartan 320 mg qd during wash-out, and Valsartan 320 mg qd double blind treatment during period 2.	8
Valsartan to LCZ696 - HTN Cohort Participants in this arm received Valsartan 320 mg qd during open-label run-in, Valsartan 320 mg qd during period 1, Valsartan 320 mg qd during wash-out, and LCZ696 400 qd bid double blind treatment during period 2.	8
Total	32

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Period 1 - First Intervention (7 Days)	Adverse Event	0	0	0	1
Period 2 - Second Intervention (7 Days)	Withdrawal by Subject	1	0	0	0

Baseline characteristics

Characteristic	LCZ696 to Valsartan - Heart Failure (HF) Cohort	Valsartan to LCZ696 - HF Cohort	LCZ696 to Valsartan - Hypertension (HTN) Cohort	Valsartan to LCZ696 - HTN Cohort	Total
Age, Continuous	63.3 Years STANDARD_DEVIATION 10.15	67.6 Years STANDARD_DEVIATION 9.07	58.0 Years STANDARD_DEVIATION 8.02	61.6 Years STANDARD_DEVIATION 8.4	62.6 Years STANDARD_DEVIATION 8.86
Sex: Female, Male Female	2 Participants	0 Participants	5 Participants	2 Participants	9 Participants
Sex: Female, Male Male	6 Participants	8 Participants	3 Participants	6 Participants	23 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —
other Total, other adverse events	3 / 16	1 / 15	1 / 15	3 / 16
serious Total, serious adverse events	0 / 16	0 / 15	0 / 15	0 / 16

Outcome results

Primary

24-hour Urinary Sodium Excretion

Urine was collected in 12-hour intervals, and of each pooled 24-hour (daily) sample, sodium concentration was measured. The measure type used for this outcome measure (OM) was Geometric Least square Means (LSM).

Time frame: day 1

Population: The Pharmacodynamic (PD) analysis set, which included all participants who had no major protocol deviation with impact on PD data, were included in the analysis.

Arm	Measure	Value (LEAST_SQUARES_MEAN)
LCZ696 - Heart Failure (HF) Cohort	24-hour Urinary Sodium Excretion	220.58 mmol/24 hours
Valsartan - HF Cohort	24-hour Urinary Sodium Excretion	198.73 mmol/24 hours
LCZ696 - Hypertension (HTN) Cohort	24-hour Urinary Sodium Excretion	177.40 mmol/24 hours
Valsartan - HTN Cohort	24-hour Urinary Sodium Excretion	146.18 mmol/24 hours

Primary

Cumulative 7-day Urinary Sodium Excretion

Time frame: 7 day-cummulative (days 1 through 7)

Population: The Pharmacodynamic (PD) analysis set, which included all participants who had no major protocol deviation with impact on PD data, were included in the analysis.

Arm	Measure	Value (LEAST_SQUARES_MEAN)
LCZ696 - Heart Failure (HF) Cohort	Cumulative 7-day Urinary Sodium Excretion	1020.57 mmol/7 days
Valsartan - HF Cohort	Cumulative 7-day Urinary Sodium Excretion	1114.18 mmol/7 days
LCZ696 - Hypertension (HTN) Cohort	Cumulative 7-day Urinary Sodium Excretion	906.81 mmol/7 days
Valsartan - HTN Cohort	Cumulative 7-day Urinary Sodium Excretion	943.26 mmol/7 days

Secondary

24-hour Diuresis

Urine was collected in 12-hour intervals, and of each pooled 24-hour (daily) sample, urine volume was measured. The measure type used for this OM was Geometric LSM.

Time frame: day 1

Population: The Pharmacodynamic (PD) analysis set, which included all participants who had no major protocol deviation with impact on PD data, were included in the analysis.

Arm	Measure	Value (LEAST_SQUARES_MEAN)
LCZ696 - Heart Failure (HF) Cohort	24-hour Diuresis	3199.37 mL/24 hours
Valsartan - HF Cohort	24-hour Diuresis	2874.36 mL/24 hours
LCZ696 - Hypertension (HTN) Cohort	24-hour Diuresis	3382.94 mL/24 hours
Valsartan - HTN Cohort	24-hour Diuresis	2393.61 mL/24 hours

Secondary

7-day Cumulative Diuresis

Urine was collected in 12-hour intervals, and of each pooled 24-hour (daily) sample, urine volume was measured. The measure type used for this OM was Geometric LSM.

Time frame: 7-day cumulative (days 1 through 7)

Population: The Pharmacodynamic (PD) analysis set, which included all participants who had no major protocol deviation with impact on PD data, were included in the analysis.

Arm	Measure	Value (LEAST_SQUARES_MEAN)
LCZ696 - Heart Failure (HF) Cohort	7-day Cumulative Diuresis	12347.92 mL
Valsartan - HF Cohort	7-day Cumulative Diuresis	13180.02 mL
LCZ696 - Hypertension (HTN) Cohort	7-day Cumulative Diuresis	16980.05 mL
Valsartan - HTN Cohort	7-day Cumulative Diuresis	15265.35 mL

Secondary

Glomerular Filtration Rate (GFR) Over Time

GFR was used as a measure of renal function.

Time frame: 0, 2, 4 and 6 hours post dose on day 1; 0, 2, 4 and 6 hours post dose on day 7

Population: The Pharmacodynamic (PD) analysis set, which included all participants who had no major protocol deviation with impact on PD data, were included in the analysis.

Arm	Measure	Group	Value (MEAN)	Dispersion
LCZ696 - Heart Failure (HF) Cohort	Glomerular Filtration Rate (GFR) Over Time	Day 7, 2 hours post dose	95.9 mL/min	Standard Deviation 39.47
LCZ696 - Heart Failure (HF) Cohort	Glomerular Filtration Rate (GFR) Over Time	Day 1, 0 hour	76.4 mL/min	Standard Deviation 43.27
LCZ696 - Heart Failure (HF) Cohort	Glomerular Filtration Rate (GFR) Over Time	Day 7, 0 hour	93.7 mL/min	Standard Deviation 75.98
LCZ696 - Heart Failure (HF) Cohort	Glomerular Filtration Rate (GFR) Over Time	Day 7, 4 hours post dose	89.6 mL/min	Standard Deviation 52.23
LCZ696 - Heart Failure (HF) Cohort	Glomerular Filtration Rate (GFR) Over Time	Day 1, 2 hours post dose	115.7 mL/min	Standard Deviation 57.89
LCZ696 - Heart Failure (HF) Cohort	Glomerular Filtration Rate (GFR) Over Time	Day 7, 6 hours post dose	86.9 mL/min	Standard Deviation 49.26
LCZ696 - Heart Failure (HF) Cohort	Glomerular Filtration Rate (GFR) Over Time	Day 1, 4 hours post dose	117.4 mL/min	Standard Deviation 75.09
LCZ696 - Heart Failure (HF) Cohort	Glomerular Filtration Rate (GFR) Over Time	Day 1, 6 hours post dose	120.2 mL/min	Standard Deviation 68.73
Valsartan - HF Cohort	Glomerular Filtration Rate (GFR) Over Time	Day 7, 6 hours post dose	126.6 mL/min	Standard Deviation 79.95
Valsartan - HF Cohort	Glomerular Filtration Rate (GFR) Over Time	Day 1, 6 hours post dose	71.7 mL/min	Standard Deviation 37.27
Valsartan - HF Cohort	Glomerular Filtration Rate (GFR) Over Time	Day 1, 2 hours post dose	83.3 mL/min	Standard Deviation 46.57
Valsartan - HF Cohort	Glomerular Filtration Rate (GFR) Over Time	Day 7, 0 hour	87.8 mL/min	Standard Deviation 57.47
Valsartan - HF Cohort	Glomerular Filtration Rate (GFR) Over Time	Day 1, 4 hours post dose	70.9 mL/min	Standard Deviation 36.64
Valsartan - HF Cohort	Glomerular Filtration Rate (GFR) Over Time	Day 1, 0 hour	92.5 mL/min	Standard Deviation 97.37
Valsartan - HF Cohort	Glomerular Filtration Rate (GFR) Over Time	Day 7, 4 hours post dose	94.6 mL/min	Standard Deviation 53.43
Valsartan - HF Cohort	Glomerular Filtration Rate (GFR) Over Time	Day 7, 2 hours post dose	83.1 mL/min	Standard Deviation 35.65
LCZ696 - Hypertension (HTN) Cohort	Glomerular Filtration Rate (GFR) Over Time	Day 7, 4 hours post dose	151.7 mL/min	Standard Deviation 109.91
LCZ696 - Hypertension (HTN) Cohort	Glomerular Filtration Rate (GFR) Over Time	Day 1, 0 hour	87.6 mL/min	Standard Deviation 64.27
LCZ696 - Hypertension (HTN) Cohort	Glomerular Filtration Rate (GFR) Over Time	Day 1, 2 hours post dose	112.1 mL/min	Standard Deviation 63.3
LCZ696 - Hypertension (HTN) Cohort	Glomerular Filtration Rate (GFR) Over Time	Day 1, 4 hours post dose	125.4 mL/min	Standard Deviation 95.33
LCZ696 - Hypertension (HTN) Cohort	Glomerular Filtration Rate (GFR) Over Time	Day 1, 6 hours post dose	148.4 mL/min	Standard Deviation 138.66
LCZ696 - Hypertension (HTN) Cohort	Glomerular Filtration Rate (GFR) Over Time	Day 7, 0 hour	96.8 mL/min	Standard Deviation 78.65
LCZ696 - Hypertension (HTN) Cohort	Glomerular Filtration Rate (GFR) Over Time	Day 7, 2 hours post dose	133.5 mL/min	Standard Deviation 67.82
LCZ696 - Hypertension (HTN) Cohort	Glomerular Filtration Rate (GFR) Over Time	Day 7, 6 hours post dose	111.5 mL/min	Standard Deviation 66.3
Valsartan - HTN Cohort	Glomerular Filtration Rate (GFR) Over Time	Day 1, 4 hours post dose	101.8 mL/min	Standard Deviation 65.34
Valsartan - HTN Cohort	Glomerular Filtration Rate (GFR) Over Time	Day 1, 2 hours post dose	96.0 mL/min	Standard Deviation 44.23
Valsartan - HTN Cohort	Glomerular Filtration Rate (GFR) Over Time	Day 7, 6 hours post dose	165.2 mL/min	Standard Deviation 228.97
Valsartan - HTN Cohort	Glomerular Filtration Rate (GFR) Over Time	Day 7, 2 hours post dose	91.4 mL/min	Standard Deviation 50.57
Valsartan - HTN Cohort	Glomerular Filtration Rate (GFR) Over Time	Day 1, 0 hour	99.2 mL/min	Standard Deviation 66.36
Valsartan - HTN Cohort	Glomerular Filtration Rate (GFR) Over Time	Day 1, 6 hours post dose	123.0 mL/min	Standard Deviation 60.62
Valsartan - HTN Cohort	Glomerular Filtration Rate (GFR) Over Time	Day 7, 4 hours post dose	111.3 mL/min	Standard Deviation 59.41
Valsartan - HTN Cohort	Glomerular Filtration Rate (GFR) Over Time	Day 7, 0 hour	83.2 mL/min	Standard Deviation 53.11

Secondary

Percent Change From Baseline in Aldosterone Biomarker

Aldosterone was analyzed at a central laboratory.

Time frame: 6 and 12 hours post dose on day 1; 24 hours post dose on day 2; 0, 6 and 12 hours post dose on day 7

Population: The Pharmacodynamic (PD) analysis set, which included all participants who had no major protocol deviation with impact on PD data, were included in the analysis.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Aldosterone Biomarker	Day 1, 6.0 hours post dose	71.15 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Aldosterone Biomarker	Day 1, 12.0 hours post dose	208.06 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Aldosterone Biomarker	Day 2, 24.0 hours post dose	168.32 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Aldosterone Biomarker	Day 7, 0.0 hour	111.21 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Aldosterone Biomarker	Day 7, 6.0 hours post dose	65.22 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Aldosterone Biomarker	Day 7, 12.0 hours post dose	238.32 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Aldosterone Biomarker	Day 7, 12.0 hours post dose	230.06 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Aldosterone Biomarker	Day 7, 0.0 hour	21.68 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Aldosterone Biomarker	Day 1, 6.0 hours post dose	-14.63 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Aldosterone Biomarker	Day 2, 24.0 hours post dose	71.73 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Aldosterone Biomarker	Day 1, 12.0 hours post dose	8.36 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Aldosterone Biomarker	Day 7, 6.0 hours post dose	24.58 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Aldosterone Biomarker	Day 1, 12.0 hours post dose	249.13 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Aldosterone Biomarker	Day 2, 24.0 hours post dose	438.28 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Aldosterone Biomarker	Day 7, 0.0 hour	49.91 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Aldosterone Biomarker	Day 7, 12.0 hours post dose	147.89 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Aldosterone Biomarker	Day 7, 6.0 hours post dose	24.47 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Aldosterone Biomarker	Day 1, 6.0 hours post dose	90.51 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Aldosterone Biomarker	Day 7, 6.0 hours post dose	107.60 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Aldosterone Biomarker	Day 7, 12.0 hours post dose	152.37 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Aldosterone Biomarker	Day 1, 12.0 hours post dose	325.31 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Aldosterone Biomarker	Day 7, 0.0 hour	5.61 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Aldosterone Biomarker	Day 1, 6.0 hours post dose	72.92 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Aldosterone Biomarker	Day 2, 24.0 hours post dose	524.93 Percentage change

Secondary

Percent Change From Baseline in Blood Plasma Creatinine

Blood plasma creatinine was analyzed at a central laboratory.

Time frame: 4, 6 and 12 hours post dose on day 1; 24 hours post dose on day 2; 0, 4, 6 and 12 hours post dose on day 7

Population: The Pharmacodynamic (PD) analysis set, which included all participants who had no major protocol deviation with impact on PD data, were included in the analysis.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Blood Plasma Creatinine	Day 1, 4.0 hours post dose	-7.06 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Blood Plasma Creatinine	Day 1, 6.0 hrs post dose	-2.97 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Blood Plasma Creatinine	Day 1, 12.0 hrs post dose	3.02 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Blood Plasma Creatinine	Day 2, 24 hrs post dose	3.73 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Blood Plasma Creatinine	Day 7, 0.0 hour	4.24 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Blood Plasma Creatinine	Day 7, 4.0 hrs post dose	-1.47 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Blood Plasma Creatinine	Day 7, 6.0 hrs post dose	1.72 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Blood Plasma Creatinine	Day 7, 12 hrs post dose	8.03 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Blood Plasma Creatinine	Day 7, 4.0 hrs post dose	-5.09 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Blood Plasma Creatinine	Day 7, 0.0 hour	0.55 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Blood Plasma Creatinine	Day 1, 6.0 hrs post dose	-0.07 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Blood Plasma Creatinine	Day 7, 12 hrs post dose	8.34 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Blood Plasma Creatinine	Day 7, 6.0 hrs post dose	-0.25 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Blood Plasma Creatinine	Day 2, 24 hrs post dose	4.02 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Blood Plasma Creatinine	Day 1, 12.0 hrs post dose	5.36 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Blood Plasma Creatinine	Day 1, 4.0 hours post dose	-3.55 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Blood Plasma Creatinine	Day 7, 6.0 hrs post dose	0.48 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Blood Plasma Creatinine	Day 1, 12.0 hrs post dose	6.22 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Blood Plasma Creatinine	Day 2, 24 hrs post dose	13.64 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Blood Plasma Creatinine	Day 7, 0.0 hour	1.76 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Blood Plasma Creatinine	Day 7, 4.0 hrs post dose	-3.02 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Blood Plasma Creatinine	Day 7, 12 hrs post dose	9.33 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Blood Plasma Creatinine	Day 1, 4.0 hours post dose	-7.48 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Blood Plasma Creatinine	Day 1, 6.0 hrs post dose	-1.72 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Blood Plasma Creatinine	Day 1, 12.0 hrs post dose	9.23 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Blood Plasma Creatinine	Day 2, 24 hrs post dose	6.18 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Blood Plasma Creatinine	Day 1, 6.0 hrs post dose	4.40 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Blood Plasma Creatinine	Day 1, 4.0 hours post dose	-0.91 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Blood Plasma Creatinine	Day 7, 0.0 hour	1.71 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Blood Plasma Creatinine	Day 7, 12 hrs post dose	4.55 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Blood Plasma Creatinine	Day 7, 6.0 hrs post dose	3.03 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Blood Plasma Creatinine	Day 7, 4.0 hrs post dose	-1.28 Percentage change

Secondary

Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker

BNP was analyzed at a central laboratory.

Time frame: 0.5, 1, 2, 4, 6 and 12 hours post dose on day 1; 24 hours post dose on day 2; 0, 4, 6 and 12 hours post dose on day 7

Population: The Pharmacodynamic (PD) analysis set, which included all participants who had no major protocol deviation with impact on PD data, were included in the analysis.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 1, 0.5 hour post dose	72.32 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 1, 4.0 hrs post dose	50.12 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 7, 0.0 hr	190.96 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 1, 1.0 hr post dose	121.85 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 2, 24 hrs post dose	102.88 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 1, 6.0 hrs post dose	130.62 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 1, 2.0 hours post dose	176.35 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 7, 12.0 hrs post dose	236.05 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 7, 6.0 hrs post dose	195.06 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 1, 12.0 hrs post dose	90.58 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 7, 4.0 hrs post dose	220.38 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 1, 12.0 hrs post dose	30.07 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 7, 4.0 hrs post dose	34.44 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 2, 24 hrs post dose	5.18 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 7, 0.0 hr	27.75 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 1, 2.0 hours post dose	21.92 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 7, 12.0 hrs post dose	70.31 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 1, 4.0 hrs post dose	-1.78 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 7, 6.0 hrs post dose	46.75 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 1, 6.0 hrs post dose	11.09 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 1, 1.0 hr post dose	-0.83 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 1, 0.5 hour post dose	-8.93 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 7, 6.0 hrs post dose	7.78 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 1, 0.5 hour post dose	-10.75 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 1, 1.0 hr post dose	1218.56 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 1, 2.0 hours post dose	31.10 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 1, 4.0 hrs post dose	38.82 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 1, 6.0 hrs post dose	68.23 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 1, 12.0 hrs post dose	85.93 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 2, 24 hrs post dose	-0.66 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 7, 0.0 hr	14.20 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 7, 4.0 hrs post dose	34.92 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 7, 12.0 hrs post dose	38.45 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 1, 12.0 hrs post dose	8.51 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 7, 12.0 hrs post dose	25.79 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 7, 4.0 hrs post dose	5.20 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 1, 6.0 hrs post dose	7.97 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 1, 4.0 hrs post dose	11.06 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 1, 2.0 hours post dose	-0.38 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 7, 6.0 hrs post dose	7.82 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 1, 1.0 hr post dose	-33.19 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 1, 0.5 hour post dose	-5.94 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 7, 0.0 hr	-7.19 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker	Day 2, 24 hrs post dose	-20.61 Percentage change

Secondary

Percent Change From Baseline in C-terminal-proendothelin-1 (CT-proET-1) Biomarker

CT-proET-1 was analyzed at a central laboratory.

Time frame: 12 hours post dose on day 1; 24 hours post dose on day 2; 0 and 12 hours post dose on day 7

Population: The Pharmacodynamic (PD) analysis set, which included all participants who had no major protocol deviation with impact on PD data, were included in the analysis.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in C-terminal-proendothelin-1 (CT-proET-1) Biomarker	Day 1, 12.0 hours post dose	36.39 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in C-terminal-proendothelin-1 (CT-proET-1) Biomarker	Day 2, 24.0 hours post dose	32.44 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in C-terminal-proendothelin-1 (CT-proET-1) Biomarker	Day 7, 0.0 hour	31.98 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in C-terminal-proendothelin-1 (CT-proET-1) Biomarker	Day 7, 12.0 hours post dose	41.75 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in C-terminal-proendothelin-1 (CT-proET-1) Biomarker	Day 2, 24.0 hours post dose	11.41 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in C-terminal-proendothelin-1 (CT-proET-1) Biomarker	Day 7, 0.0 hour	0.62 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in C-terminal-proendothelin-1 (CT-proET-1) Biomarker	Day 7, 12.0 hours post dose	7.05 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in C-terminal-proendothelin-1 (CT-proET-1) Biomarker	Day 1, 12.0 hours post dose	2.51 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in C-terminal-proendothelin-1 (CT-proET-1) Biomarker	Day 7, 0.0 hour	94.76 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in C-terminal-proendothelin-1 (CT-proET-1) Biomarker	Day 2, 24.0 hours post dose	123.45 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in C-terminal-proendothelin-1 (CT-proET-1) Biomarker	Day 7, 12.0 hours post dose	117.84 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in C-terminal-proendothelin-1 (CT-proET-1) Biomarker	Day 1, 12.0 hours post dose	108.87 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in C-terminal-proendothelin-1 (CT-proET-1) Biomarker	Day 7, 12.0 hours post dose	61.90 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in C-terminal-proendothelin-1 (CT-proET-1) Biomarker	Day 2, 24.0 hours post dose	38.70 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in C-terminal-proendothelin-1 (CT-proET-1) Biomarker	Day 1, 12.0 hours post dose	54.07 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in C-terminal-proendothelin-1 (CT-proET-1) Biomarker	Day 7, 0.0 hour	41.77 Percentage change

Secondary

Percent Change From Baseline in C-type Natriuretic Peptide (proCNP) Biomarker

ProCNP was analyzed at a central laboratory.

Time frame: 2, 4, 6, 8 and 12 hours post dose on day 1; day 2; 0, 4, 6, 8 and 12 hours post dose on day 7

Population: The HF arms only of the Pharmacodynamic (PD) analysis set, which included all participants who had no major protocol deviation with impact on PD data, were included in the analysis. MR-proADM is considered a biomarker for HF only; therefore, the HTN cohort was not assessed.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in C-type Natriuretic Peptide (proCNP) Biomarker	Day 1, 8.0 hrs post dose	123.75 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in C-type Natriuretic Peptide (proCNP) Biomarker	Day 7, 0.0 hour	244.20 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in C-type Natriuretic Peptide (proCNP) Biomarker	Day 1, 6.0 hrs post dose	67.85 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in C-type Natriuretic Peptide (proCNP) Biomarker	Day 7, 4.0 hours post dose	216.61 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in C-type Natriuretic Peptide (proCNP) Biomarker	Day 1, 12.0 hrs post dose	190.36 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in C-type Natriuretic Peptide (proCNP) Biomarker	Day 7, 6.0 hrs post dose	211.21 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in C-type Natriuretic Peptide (proCNP) Biomarker	Day 1, 4.0 hours post dose	34.58 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in C-type Natriuretic Peptide (proCNP) Biomarker	Day 7, 8.0 hrs post dose	241.99 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in C-type Natriuretic Peptide (proCNP) Biomarker	Day 2, 24 hrs post dose	218.81 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in C-type Natriuretic Peptide (proCNP) Biomarker	Day 7, 12.0 hrs post dose	278.58 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in C-type Natriuretic Peptide (proCNP) Biomarker	Day 1, 2.0 hrs post dose	0.35 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in C-type Natriuretic Peptide (proCNP) Biomarker	Day 7, 12.0 hrs post dose	0.88 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in C-type Natriuretic Peptide (proCNP) Biomarker	Day 1, 2.0 hrs post dose	-1.01 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in C-type Natriuretic Peptide (proCNP) Biomarker	Day 1, 4.0 hours post dose	-6.02 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in C-type Natriuretic Peptide (proCNP) Biomarker	Day 1, 6.0 hrs post dose	-16.19 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in C-type Natriuretic Peptide (proCNP) Biomarker	Day 1, 8.0 hrs post dose	-9.87 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in C-type Natriuretic Peptide (proCNP) Biomarker	Day 1, 12.0 hrs post dose	15.55 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in C-type Natriuretic Peptide (proCNP) Biomarker	Day 2, 24 hrs post dose	4.99 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in C-type Natriuretic Peptide (proCNP) Biomarker	Day 7, 0.0 hour	0.09 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in C-type Natriuretic Peptide (proCNP) Biomarker	Day 7, 4.0 hours post dose	-8.94 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in C-type Natriuretic Peptide (proCNP) Biomarker	Day 7, 6.0 hrs post dose	-18.17 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in C-type Natriuretic Peptide (proCNP) Biomarker	Day 7, 8.0 hrs post dose	-11.30 Percentage change

Secondary

Percent Change From Baseline in Mid-regional Pro-adrenomedullin (MR-proADM) Biomarker

MR-proADM was analyzed at a central laboratory.

Time frame: 2, 4, 6 and 12 hours post dose on day 1; 24 hours post dose on day 2; 0, 4, 6 and 12 hours post dose on day 7

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Mid-regional Pro-adrenomedullin (MR-proADM) Biomarker	Day 1, 4.0 hrs post dose	21.22 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Mid-regional Pro-adrenomedullin (MR-proADM) Biomarker	Day 7, 0.0 hrs	61.28 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Mid-regional Pro-adrenomedullin (MR-proADM) Biomarker	Day 1, 12.0 hrs post dose	40.70 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Mid-regional Pro-adrenomedullin (MR-proADM) Biomarker	Day 7, 4.0 hrs post dose	51.71 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Mid-regional Pro-adrenomedullin (MR-proADM) Biomarker	Day 1, 6.0 hrs post dose	20.18 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Mid-regional Pro-adrenomedullin (MR-proADM) Biomarker	Day 7, 6.0 hrs post dose	48.22 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Mid-regional Pro-adrenomedullin (MR-proADM) Biomarker	Day 2, 24 hrs post dose	57.28 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Mid-regional Pro-adrenomedullin (MR-proADM) Biomarker	Day 7, 12.0 hrs post dose	69.45 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Mid-regional Pro-adrenomedullin (MR-proADM) Biomarker	Day 1, 2.0 hours post dose	8.04 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Mid-regional Pro-adrenomedullin (MR-proADM) Biomarker	Day 7, 12.0 hrs post dose	2.15 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Mid-regional Pro-adrenomedullin (MR-proADM) Biomarker	Day 1, 2.0 hours post dose	-2.87 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Mid-regional Pro-adrenomedullin (MR-proADM) Biomarker	Day 1, 4.0 hrs post dose	-8.22 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Mid-regional Pro-adrenomedullin (MR-proADM) Biomarker	Day 1, 6.0 hrs post dose	-8.81 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Mid-regional Pro-adrenomedullin (MR-proADM) Biomarker	Day 1, 12.0 hrs post dose	7.61 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Mid-regional Pro-adrenomedullin (MR-proADM) Biomarker	Day 2, 24 hrs post dose	0.72 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Mid-regional Pro-adrenomedullin (MR-proADM) Biomarker	Day 7, 0.0 hrs	1.38 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Mid-regional Pro-adrenomedullin (MR-proADM) Biomarker	Day 7, 4.0 hrs post dose	-5.27 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Mid-regional Pro-adrenomedullin (MR-proADM) Biomarker	Day 7, 6.0 hrs post dose	-3.63 Percentage change

Secondary

Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker

NT-proBNP was analyzed at a central laboratory.

Time frame: 2, 4, 6 and 12 hours post dose on day 1; 24 hours post dose on day 2; 0, 4, 6 and 12 hours post dose on day 7

Population: The Pharmacodynamic (PD) analysis set, which included all participants who had no major protocol deviation with impact on PD data, were included in the analysis.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	Day 7, 4.0 hours post dose	-14.60 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	Day 7, 0.0 hour	-19.57 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	Day 7, 12.0 hours post dose	1.37 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	Day 1, 12.0 hours post dose	17.15 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	Day 1, 6.0 hours post dose	3.71 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	Day 1, 4.0 hours post dose	2.68 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	Day 7, 6.0 hours post dose	-15.05 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	Day 2, 24 hours post dose	-21.85 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	Day 1, 2.0 hours post dose	3.06 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	Day 2, 24 hours post dose	23.51 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	Day 7, 4.0 hours post dose	14.85 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	Day 7, 0.0 hour	2.29 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	Day 1, 4.0 hours post dose	13.21 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	Day 1, 2.0 hours post dose	6.87 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	Day 1, 6.0 hours post dose	21.70 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	Day 7, 12.0 hours post dose	46.05 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	Day 7, 6.0 hours post dose	17.34 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	Day 1, 12.0 hours post dose	42.32 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	Day 2, 24 hours post dose	8.61 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	Day 1, 2.0 hours post dose	5.10 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	Day 1, 4.0 hours post dose	44.79 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	Day 1, 6.0 hours post dose	12.58 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	Day 1, 12.0 hours post dose	61.46 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	Day 7, 0.0 hour	-10.14 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	Day 7, 4.0 hours post dose	-8.10 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	Day 7, 6.0 hours post dose	-9.42 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	Day 7, 12.0 hours post dose	12.22 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	Day 7, 4.0 hours post dose	19.83 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	Day 1, 12.0 hours post dose	33.17 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	Day 1, 6.0 hours post dose	21.21 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	Day 7, 12.0 hours post dose	47.27 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	Day 7, 6.0 hours post dose	20.47 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	Day 1, 4.0 hours post dose	22.14 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	Day 7, 0.0 hour	-0.13 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	Day 2, 24 hours post dose	-4.41 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker	Day 1, 2.0 hours post dose	8.32 Percentage change

Secondary

Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker

MR-proANP was analyzed at a central laboratory.

Time frame: 2, 4, 6 and 12 hours post dose on day 1; 24 hours post dose on day 2; 2, 4, 6 and 12 hours post dose on day 7

Population: The Pharmacodynamic (PD) analysis set, which included all participants who had no major protocol deviation with impact on PD data, were included in the analysis.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	Day 7, 4.0 hours post dose	-24.35 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	Day 7, 0.0 hours	-21.27 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	Day 7, 12.0 hours post dose	-20.95 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	Day 1, 12.0 hrs post dose	-27.58 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	Day 1, 6.0 hours post dose	-23.99 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	Day 1, 4.0 hrs post dose	-17.39 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	Day 7, 6.0 hours post dose	-23.40 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	Day 2, 24.0 hrs post dose	-25.13 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	Day 1, 2.0 hours post dose	-7.04 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	Day 2, 24.0 hrs post dose	-14.53 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	Day 7, 4.0 hours post dose	1.64 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	Day 7, 0.0 hours	-2.54 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	Day 1, 4.0 hrs post dose	-6.74 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	Day 1, 2.0 hours post dose	2.08 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	Day 1, 6.0 hours post dose	-10.16 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	Day 7, 12.0 hours post dose	-12.65 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	Day 7, 6.0 hours post dose	-3.53 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	Day 1, 12.0 hrs post dose	-7.48 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	Day 2, 24.0 hrs post dose	-17.30 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	Day 1, 2.0 hours post dose	-10.11 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	Day 1, 4.0 hrs post dose	-12.68 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	Day 1, 6.0 hours post dose	-17.82 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	Day 1, 12.0 hrs post dose	-19.77 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	Day 7, 0.0 hours	-16.03 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	Day 7, 4.0 hours post dose	-19.34 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	Day 7, 6.0 hours post dose	-20.84 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	Day 7, 12.0 hours post dose	-23.09 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	Day 7, 4.0 hours post dose	-2.56 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	Day 1, 12.0 hrs post dose	-15.20 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	Day 1, 6.0 hours post dose	-4.52 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	Day 7, 12.0 hours post dose	-10.27 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	Day 7, 6.0 hours post dose	-1.98 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	Day 1, 4.0 hrs post dose	-7.33 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	Day 7, 0.0 hours	0.44 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	Day 2, 24.0 hrs post dose	-9.45 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker	Day 1, 2.0 hours post dose	-1.66 Percentage change

Secondary

Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)

Urine was collected in 12-hour intervals, and of each pooled 24-hour (daily) sample, sodium, potassium, albumin and calcium were measured.

Time frame: 2, 4, 6 and 12 hours post dose on day 1; 24 hours post dose on day 2; 0, 4, 6 and 12 hours post dose on day 7

Population: The Pharmacodynamic (PD) analysis set, which included all participants who had no major protocol deviation with impact on PD data, were included in the analysis.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Potassium, day 1, 2.0 hours post dose	1.96 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Potassium, day 1, 4.0 hours post dose	-0.16 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Calcium, day 7, 0.0 hour	-0.34 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Potassium, day 7, 12.0 hours post dose	17.22 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Potassium, day 1, 6.0 hours post dose	-2.91 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Potassium, day 1, 12.0 hours post dose	6.63 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Potassium, day 7, 6.0 hours post dose	-3.23 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Potassium, day 2, 24.0 hours post dose	2.06 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Calcium, day 1, 2.0 hours post dose	-0.05 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Potassium, day 7, 0.0 hour	1.06 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Sodium, day 7, 4.0 hours post dose	-0.25 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Potassium, day 7, 4.0 hours post dose	-2.16 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Calcium, day 7, 4.0 hours post dose	-2.45 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Sodium, day 7, 12.0 hours post dose	0.34 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Calcium, day 7, 6.0 hours post dose	-4.30 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Calcium, day 1, 6.0 hours post dose	-3.69 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Sodium, day 7, 0.0 hour	1.21 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Calcium, day 7, 12.0 hours post dose	-3.41 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Chloride, day 1, 2.0 hours post dose	-0.33 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Sodium, day 2, 24.0 hours post dose	0.03 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Chloride, day 1, 4.0 hours post dose	-1.35 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Chloride, day 1, 6.0 hours post dose	-0.66 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Calcium, day 1, 12.0 hours post dose	-2.80 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Sodium, day 1, 12.0 hours post dose	-0.17 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Chloride, day 1, 12.0 hours post dose	0.46 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Chloride, day 2, 24 hours post dose	0.49 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Calcium, day 1, 4.0 hours post dose	-2.19 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Sodium, day 1, 6.0 hours post dose	-1.47 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Chloride, day 7, 0.0 hour	1.46 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Sodium, day 7, 6.0 hours post dose	0.01 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Chloride, day 7, 4.0 hours post dose	0.47 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Calcium, day 2, 24 hours post dose	-2.09 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Sodium, day 1, 4.0 hours post dose	-1.82 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Chloride, day 7, 6.0 hours post dose	0.87 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Chloride, day 7, 12.0 hours post dose	0.98 Percentage change
LCZ696 - Heart Failure (HF) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Sodium, day 1, 2.0 hours post dose	-1.09 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Sodium, day 1, 2.0 hours post dose	-0.67 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Potassium, day 1, 2.0 hours post dose	-1.25 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Sodium, day 7, 4.0 hours post dose	-0.89 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Potassium, day 7, 12.0 hours post dose	12.32 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Chloride, day 1, 2.0 hours post dose	-0.47 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Potassium, day 1, 4.0 hours post dose	-0.11 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Sodium, day 7, 12.0 hours post dose	0.78 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Calcium, day 1, 4.0 hours post dose	-2.46 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Chloride, day 7, 12.0 hours post dose	1.20 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Potassium, day 1, 6.0 hours post dose	-5.88 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Calcium, day 7, 0.0 hour	-1.11 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Potassium, day 7, 6.0 hours post dose	-5.16 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Chloride, day 1, 4.0 hours post dose	-0.61 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Potassium, day 1, 12.0 hours post dose	15.27 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Calcium, day 1, 2.0 hours post dose	-1.40 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Sodium, day 7, 6.0 hours post dose	-0.19 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Sodium, day 1, 12.0 hours post dose	0.48 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Potassium, day 2, 24.0 hours post dose	0.14 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Chloride, day 7, 0.0 hour	1.28 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Potassium, day 7, 4.0 hours post dose	-2.93 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Chloride, day 1, 6.0 hours post dose	-0.42 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Potassium, day 7, 0.0 hour	-1.55 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Chloride, day 7, 6.0 hours post dose	1.32 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Sodium, day 1, 4.0 hours post dose	-1.18 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Calcium, day 2, 24 hours post dose	0.44 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Calcium, day 7, 4.0 hours post dose	-2.17 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Chloride, day 1, 12.0 hours post dose	1.44 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Sodium, day 7, 0.0 hour	1.36 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Calcium, day 1, 12.0 hours post dose	-1.34 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Calcium, day 7, 6.0 hours post dose	-3.53 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Sodium, day 1, 6.0 hours post dose	-1.12 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Chloride, day 7, 4.0 hours post dose	0.22 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Chloride, day 2, 24 hours post dose	0.73 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Calcium, day 7, 12.0 hours post dose	-1.27 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Calcium, day 1, 6.0 hours post dose	-4.03 Percentage change
Valsartan - HF Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Sodium, day 2, 24.0 hours post dose	1.06 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Potassium, day 2, 24.0 hours post dose	7.70 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Calcium, day 1, 2.0 hours post dose	0.51 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Calcium, day 1, 4.0 hours post dose	0.76 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Calcium, day 1, 6.0 hours post dose	-2.22 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Calcium, day 1, 12.0 hours post dose	1.77 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Calcium, day 2, 24 hours post dose	2.06 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Calcium, day 7, 0.0 hour	-5.82 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Calcium, day 7, 4.0 hours post dose	-8.46 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Calcium, day 7, 6.0 hours post dose	-9.12 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Calcium, day 7, 12.0 hours post dose	-4.63 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Chloride, day 1, 2.0 hours post dose	-0.35 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Chloride, day 1, 4.0 hours post dose	0.05 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Chloride, day 1, 6.0 hours post dose	-0.48 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Chloride, day 1, 12.0 hours post dose	-0.93 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Chloride, day 2, 24 hours post dose	0.11 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Chloride, day 7, 0.0 hour	0.89 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Chloride, day 7, 4.0 hours post dose	-0.05 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Chloride, day 7, 6.0 hours post dose	-0.21 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Chloride, day 7, 12.0 hours post dose	-1.16 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Potassium, day 1, 2.0 hours post dose	-1.20 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Potassium, day 1, 4.0 hours post dose	0.42 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Potassium, day 1, 6.0 hours post dose	-0.63 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Potassium, day 1, 12.0 hours post dose	18.57 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Potassium, day 7, 0.0 hour	-0.47 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Potassium, day 7, 4.0 hours post dose	3.61 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Potassium, day 7, 6.0 hours post dose	-4.20 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Potassium, day 7, 12.0 hours post dose	18.19 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Sodium, day 1, 2.0 hours post dose	-0.63 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Sodium, day 1, 4.0 hours post dose	-0.18 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Sodium, day 1, 6.0 hours post dose	-0.62 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Sodium, day 1, 12.0 hours post dose	-0.12 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Sodium, day 2, 24.0 hours post dose	0.85 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Sodium, day 7, 0.0 hour	0.69 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Sodium, day 7, 4.0 hours post dose	-0.81 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Sodium, day 7, 6.0 hours post dose	-0.74 Percentage change
LCZ696 - Hypertension (HTN) Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Sodium, day 7, 12.0 hours post dose	-0.41 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Chloride, day 7, 12.0 hours post dose	-1.48 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Chloride, day 7, 6.0 hours post dose	-0.86 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Sodium, day 7, 4.0 hours post dose	-0.16 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Sodium, day 1, 2.0 hours post dose	-0.17 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Chloride, day 7, 4.0 hours post dose	0.28 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Chloride, day 7, 0.0 hour	0.63 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Calcium, day 1, 12.0 hours post dose	0.82 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Sodium, day 1, 4.0 hours post dose	-0.04 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Chloride, day 2, 24 hours post dose	0.58 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Chloride, day 1, 12.0 hours post dose	-0.15 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Calcium, day 1, 6.0 hours post dose	-2.49 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Sodium, day 1, 6.0 hours post dose	-0.17 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Chloride, day 1, 6.0 hours post dose	0.05 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Chloride, day 1, 4.0 hours post dose	0.41 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Sodium, day 7, 12.0 hours post dose	-1.04 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Sodium, day 1, 12.0 hours post dose	0.14 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Chloride, day 1, 2.0 hours post dose	0.22 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Calcium, day 7, 12.0 hours post dose	-4.99 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Sodium, day 7, 6.0 hours post dose	-0.86 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Sodium, day 2, 24.0 hours post dose	1.24 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Calcium, day 7, 6.0 hours post dose	-9.89 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Calcium, day 7, 4.0 hours post dose	-7.42 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Calcium, day 1, 4.0 hours post dose	0.27 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Sodium, day 7, 0.0 hour	0.84 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Potassium, day 7, 0.0 hour	1.29 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Potassium, day 2, 24.0 hours post dose	7.00 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Calcium, day 7, 0.0 hour	-6.19 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Potassium, day 7, 4.0 hours post dose	0.28 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Potassium, day 1, 12.0 hours post dose	19.96 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Potassium, day 1, 6.0 hours post dose	-2.61 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Calcium, day 2, 24 hours post dose	1.34 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Potassium, day 7, 6.0 hours post dose	-4.14 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Potassium, day 1, 4.0 hours post dose	1.11 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Potassium, day 1, 2.0 hours post dose	1.69 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Calcium, day 1, 2.0 hours post dose	0.08 Percentage change
Valsartan - HTN Cohort	Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)	Potassium, day 7, 12.0 hours post dose	19.28 Percentage change

Secondary

Renal Blood Flow (RBF) Over Time

RBF was used as a measure of renal function.

Time frame: 0, 2, 4 and 6 hours post dose on day 1; 0, 2, 4 and 6 hours post dose on day 7

Population: The Pharmacodynamic (PD) analysis set, which included all participants who had no major protocol deviation with impact on PD data, were included in the analysis.

Arm	Measure	Group	Value (MEAN)	Dispersion
LCZ696 - Heart Failure (HF) Cohort	Renal Blood Flow (RBF) Over Time	Day 1, 0 hour	398.1 mL/min	Standard Deviation 221.24
LCZ696 - Heart Failure (HF) Cohort	Renal Blood Flow (RBF) Over Time	Day 1, 2 hours post dose	361.3 mL/min	Standard Deviation 171.8
LCZ696 - Heart Failure (HF) Cohort	Renal Blood Flow (RBF) Over Time	Day 1, 4 hours post dose	340.1 mL/min	Standard Deviation 169.87
LCZ696 - Heart Failure (HF) Cohort	Renal Blood Flow (RBF) Over Time	Day 1, 6 hours post dose	465.2 mL/min	Standard Deviation 276.84
LCZ696 - Heart Failure (HF) Cohort	Renal Blood Flow (RBF) Over Time	Day 7, 0 hour	354.9 mL/min	Standard Deviation 223.49
LCZ696 - Heart Failure (HF) Cohort	Renal Blood Flow (RBF) Over Time	Day 7, 2 hours	331.9 mL/min	Standard Deviation 180.59
LCZ696 - Heart Failure (HF) Cohort	Renal Blood Flow (RBF) Over Time	Day 7, 4 hours	324.2 mL/min	Standard Deviation 168.1
LCZ696 - Heart Failure (HF) Cohort	Renal Blood Flow (RBF) Over Time	Day 7, 6 hours	331.0 mL/min	Standard Deviation 228.38
Valsartan - HF Cohort	Renal Blood Flow (RBF) Over Time	Day 7, 2 hours	341.1 mL/min	Standard Deviation 156.86
Valsartan - HF Cohort	Renal Blood Flow (RBF) Over Time	Day 7, 0 hour	417.0 mL/min	Standard Deviation 254.35
Valsartan - HF Cohort	Renal Blood Flow (RBF) Over Time	Day 1, 2 hours post dose	357.4 mL/min	Standard Deviation 218.28
Valsartan - HF Cohort	Renal Blood Flow (RBF) Over Time	Day 7, 6 hours	440.8 mL/min	Standard Deviation 310.64
Valsartan - HF Cohort	Renal Blood Flow (RBF) Over Time	Day 7, 4 hours	285.9 mL/min	Standard Deviation 150.82
Valsartan - HF Cohort	Renal Blood Flow (RBF) Over Time	Day 1, 6 hours post dose	290.05 mL/min	Standard Deviation 138.3
Valsartan - HF Cohort	Renal Blood Flow (RBF) Over Time	Day 1, 4 hours post dose	297.4 mL/min	Standard Deviation 219.83
Valsartan - HF Cohort	Renal Blood Flow (RBF) Over Time	Day 1, 0 hour	305.7 mL/min	Standard Deviation 159.44
LCZ696 - Hypertension (HTN) Cohort	Renal Blood Flow (RBF) Over Time	Day 7, 4 hours	653.2 mL/min	Standard Deviation 412.91
LCZ696 - Hypertension (HTN) Cohort	Renal Blood Flow (RBF) Over Time	Day 1, 4 hours post dose	700.0 mL/min	Standard Deviation 408.73
LCZ696 - Hypertension (HTN) Cohort	Renal Blood Flow (RBF) Over Time	Day 1, 6 hours post dose	1165.2 mL/min	Standard Deviation 912.25
LCZ696 - Hypertension (HTN) Cohort	Renal Blood Flow (RBF) Over Time	Day 7, 0 hour	548.5 mL/min	Standard Deviation 389.77
LCZ696 - Hypertension (HTN) Cohort	Renal Blood Flow (RBF) Over Time	Day 7, 2 hours	630.4 mL/min	Standard Deviation 239.55
LCZ696 - Hypertension (HTN) Cohort	Renal Blood Flow (RBF) Over Time	Day 7, 6 hours	667.6 mL/min	Standard Deviation 308.52
LCZ696 - Hypertension (HTN) Cohort	Renal Blood Flow (RBF) Over Time	Day 1, 0 hour	774.7 mL/min	Standard Deviation 893.23
LCZ696 - Hypertension (HTN) Cohort	Renal Blood Flow (RBF) Over Time	Day 1, 2 hours post dose	570.5 mL/min	Standard Deviation 212.67
Valsartan - HTN Cohort	Renal Blood Flow (RBF) Over Time	Day 1, 4 hours post dose	573.4 mL/min	Standard Deviation 287.14
Valsartan - HTN Cohort	Renal Blood Flow (RBF) Over Time	Day 1, 6 hours post dose	758.7 mL/min	Standard Deviation 375.11
Valsartan - HTN Cohort	Renal Blood Flow (RBF) Over Time	Day 1, 2 hours post dose	541.7 mL/min	Standard Deviation 179.2
Valsartan - HTN Cohort	Renal Blood Flow (RBF) Over Time	Day 1, 0 hour	737.0 mL/min	Standard Deviation 323.14
Valsartan - HTN Cohort	Renal Blood Flow (RBF) Over Time	Day 7, 0 hour	549.3 mL/min	Standard Deviation 247.41
Valsartan - HTN Cohort	Renal Blood Flow (RBF) Over Time	Day 7, 6 hours	977.9 mL/min	Standard Deviation 975.25
Valsartan - HTN Cohort	Renal Blood Flow (RBF) Over Time	Day 7, 4 hours	606.3 mL/min	Standard Deviation 224.57
Valsartan - HTN Cohort	Renal Blood Flow (RBF) Over Time	Day 7, 2 hours	659.1 mL/min	Standard Deviation 426.18

Secondary

Supine Diastolic Blood Pressure

Diastolic blood pressure measurements were taken.

Time frame: 0, 0.5, 1, 2, 4, 8 and 12 hours post dose on day 1; day 2; 0, 0.5, 1, 2, 4, 8 and 12 hours post dose on day 7

Population: The Pharmacodynamic (PD) analysis set, which included all participants who had no major protocol deviation with impact on PD data, were included in the analysis.

Arm	Measure	Group	Value (MEAN)	Dispersion
LCZ696 - Heart Failure (HF) Cohort	Supine Diastolic Blood Pressure	Day 7, 0.0 hour	66.9 mmHg	Standard Deviation 11.04
LCZ696 - Heart Failure (HF) Cohort	Supine Diastolic Blood Pressure	Day 2	71.6 mmHg	Standard Deviation 10.03
LCZ696 - Heart Failure (HF) Cohort	Supine Diastolic Blood Pressure	Day 1, 4.0 hours post dose	75.6 mmHg	Standard Deviation 13.77
LCZ696 - Heart Failure (HF) Cohort	Supine Diastolic Blood Pressure	Day 7, 12.0 hours post dose	65.3 mmHg	Standard Deviation 10.95
LCZ696 - Heart Failure (HF) Cohort	Supine Diastolic Blood Pressure	Day 1, 12.0 hours post dose	65.4 mmHg	Standard Deviation 11.49
LCZ696 - Heart Failure (HF) Cohort	Supine Diastolic Blood Pressure	Day 1, 8.0 hours post dose	68.5 mmHg	Standard Deviation 11.15
LCZ696 - Heart Failure (HF) Cohort	Supine Diastolic Blood Pressure	Day 7, 4.0 hours post dose	69.6 mmHg	Standard Deviation 11.17
LCZ696 - Heart Failure (HF) Cohort	Supine Diastolic Blood Pressure	Day 1, 0.0 hour	68.2 mmHg	Standard Deviation 9.85
LCZ696 - Heart Failure (HF) Cohort	Supine Diastolic Blood Pressure	Day 1, 1.0 hour post dose	71.3 mmHg	Standard Deviation 12
LCZ696 - Heart Failure (HF) Cohort	Supine Diastolic Blood Pressure	Day 7, 8.0 hours post dose	69.3 mmHg	Standard Deviation 10.08
LCZ696 - Heart Failure (HF) Cohort	Supine Diastolic Blood Pressure	Day 7, 1.0 hour post dose	69.3 mmHg	Standard Deviation 10.49
LCZ696 - Heart Failure (HF) Cohort	Supine Diastolic Blood Pressure	Day 7, 0.5 hour post dose	69.6 mmHg	Standard Deviation 11.74
LCZ696 - Heart Failure (HF) Cohort	Supine Diastolic Blood Pressure	Day 7, 2.0 hours post dose	70.6 mmHg	Standard Deviation 11.85
LCZ696 - Heart Failure (HF) Cohort	Supine Diastolic Blood Pressure	Day 1, 2.0 hours post dose	73.3 mmHg	Standard Deviation 12.01
LCZ696 - Heart Failure (HF) Cohort	Supine Diastolic Blood Pressure	Day 1, 0.5 hour post dose	71.2 mmHg	Standard Deviation 12
Valsartan - HF Cohort	Supine Diastolic Blood Pressure	Day 7, 2.0 hours post dose	76.7 mmHg	Standard Deviation 9.15
Valsartan - HF Cohort	Supine Diastolic Blood Pressure	Day 1, 0.0 hour	74.1 mmHg	Standard Deviation 13.2
Valsartan - HF Cohort	Supine Diastolic Blood Pressure	Day 1, 0.5 hour post dose	75.5 mmHg	Standard Deviation 13.77
Valsartan - HF Cohort	Supine Diastolic Blood Pressure	Day 1, 1.0 hour post dose	75.8 mmHg	Standard Deviation 13.73
Valsartan - HF Cohort	Supine Diastolic Blood Pressure	Day 1, 2.0 hours post dose	77.1 mmHg	Standard Deviation 10.61
Valsartan - HF Cohort	Supine Diastolic Blood Pressure	Day 1, 4.0 hours post dose	79.1 mmHg	Standard Deviation 12.21
Valsartan - HF Cohort	Supine Diastolic Blood Pressure	Day 1, 8.0 hours post dose	70.4 mmHg	Standard Deviation 11.12
Valsartan - HF Cohort	Supine Diastolic Blood Pressure	Day 1, 12.0 hours post dose	71.7 mmHg	Standard Deviation 13.43
Valsartan - HF Cohort	Supine Diastolic Blood Pressure	Day 2	74.9 mmHg	Standard Deviation 13.33
Valsartan - HF Cohort	Supine Diastolic Blood Pressure	Day 7, 0.0 hour	68.4 mmHg	Standard Deviation 11.37
Valsartan - HF Cohort	Supine Diastolic Blood Pressure	Day 7, 0.5 hour post dose	73.9 mmHg	Standard Deviation 9.48
Valsartan - HF Cohort	Supine Diastolic Blood Pressure	Day 7, 1.0 hour post dose	73.9 mmHg	Standard Deviation 8.94
Valsartan - HF Cohort	Supine Diastolic Blood Pressure	Day 7, 4.0 hours post dose	74.5 mmHg	Standard Deviation 10.86
Valsartan - HF Cohort	Supine Diastolic Blood Pressure	Day 7, 8.0 hours post dose	71.5 mmHg	Standard Deviation 8.43
Valsartan - HF Cohort	Supine Diastolic Blood Pressure	Day 7, 12.0 hours post dose	69.8 mmHg	Standard Deviation 12.39
LCZ696 - Hypertension (HTN) Cohort	Supine Diastolic Blood Pressure	Day 1, 2.0 hours post dose	77.6 mmHg	Standard Deviation 11.79
LCZ696 - Hypertension (HTN) Cohort	Supine Diastolic Blood Pressure	Day 7, 2.0 hours post dose	72.0 mmHg	Standard Deviation 8.2
LCZ696 - Hypertension (HTN) Cohort	Supine Diastolic Blood Pressure	Day 7, 8.0 hours post dose	71.4 mmHg	Standard Deviation 7.84
LCZ696 - Hypertension (HTN) Cohort	Supine Diastolic Blood Pressure	Day 1, 0.5 hour post dose	76.3 mmHg	Standard Deviation 11.85
LCZ696 - Hypertension (HTN) Cohort	Supine Diastolic Blood Pressure	Day 7, 0.5 hour post dose	74.3 mmHg	Standard Deviation 9.36
LCZ696 - Hypertension (HTN) Cohort	Supine Diastolic Blood Pressure	Day 7, 4.0 hours post dose	74.4 mmHg	Standard Deviation 9.6
LCZ696 - Hypertension (HTN) Cohort	Supine Diastolic Blood Pressure	Day 7, 0.0 hour	74.7 mmHg	Standard Deviation 8.77
LCZ696 - Hypertension (HTN) Cohort	Supine Diastolic Blood Pressure	Day 1, 1.0 hour post dose	75.3 mmHg	Standard Deviation 10.37
LCZ696 - Hypertension (HTN) Cohort	Supine Diastolic Blood Pressure	Day 1, 8.0 hours post dose	75.2 mmHg	Standard Deviation 10.23
LCZ696 - Hypertension (HTN) Cohort	Supine Diastolic Blood Pressure	Day 1, 0.0 hour	77.6 mmHg	Standard Deviation 10.57
LCZ696 - Hypertension (HTN) Cohort	Supine Diastolic Blood Pressure	Day 1, 4.0 hours post dose	80.0 mmHg	Standard Deviation 13.6
LCZ696 - Hypertension (HTN) Cohort	Supine Diastolic Blood Pressure	Day 7, 1.0 hour post dose	73.5 mmHg	Standard Deviation 8.52
LCZ696 - Hypertension (HTN) Cohort	Supine Diastolic Blood Pressure	Day 1, 12.0 hours post dose	75.5 mmHg	Standard Deviation 8.33
LCZ696 - Hypertension (HTN) Cohort	Supine Diastolic Blood Pressure	Day 2	73.2 mmHg	Standard Deviation 10.78
LCZ696 - Hypertension (HTN) Cohort	Supine Diastolic Blood Pressure	Day 7, 12.0 hours post dose	70.7 mmHg	Standard Deviation 8.36
Valsartan - HTN Cohort	Supine Diastolic Blood Pressure	Day 1, 2.0 hours post dose	76.0 mmHg	Standard Deviation 10.78
Valsartan - HTN Cohort	Supine Diastolic Blood Pressure	Day 2	75.1 mmHg	Standard Deviation 8.35
Valsartan - HTN Cohort	Supine Diastolic Blood Pressure	Day 7, 0.0 hour	74.7 mmHg	Standard Deviation 9.62
Valsartan - HTN Cohort	Supine Diastolic Blood Pressure	Day 1, 1.0 hour post dose	76.2 mmHg	Standard Deviation 9.59
Valsartan - HTN Cohort	Supine Diastolic Blood Pressure	Day 7, 8.0 hours post dose	75.3 mmHg	Standard Deviation 8.5
Valsartan - HTN Cohort	Supine Diastolic Blood Pressure	Day 7, 0.5 hour post dose	74.5 mmHg	Standard Deviation 9.65
Valsartan - HTN Cohort	Supine Diastolic Blood Pressure	Day 7, 1.0 hour post dose	75.1 mmHg	Standard Deviation 8.71
Valsartan - HTN Cohort	Supine Diastolic Blood Pressure	Day 1, 0.5 hour post dose	75.8 mmHg	Standard Deviation 10.67
Valsartan - HTN Cohort	Supine Diastolic Blood Pressure	Day 7, 2.0 hours post dose	78.8 mmHg	Standard Deviation 9.29
Valsartan - HTN Cohort	Supine Diastolic Blood Pressure	Day 7, 12.0 hours post dose	75.7 mmHg	Standard Deviation 11.47
Valsartan - HTN Cohort	Supine Diastolic Blood Pressure	Day 1, 4.0 hours post dose	79.9 mmHg	Standard Deviation 9.08
Valsartan - HTN Cohort	Supine Diastolic Blood Pressure	Day 7, 4.0 hours post dose	78.4 mmHg	Standard Deviation 9.77
Valsartan - HTN Cohort	Supine Diastolic Blood Pressure	Day 1, 8.0 hours post dose	76.2 mmHg	Standard Deviation 8.89
Valsartan - HTN Cohort	Supine Diastolic Blood Pressure	Day 1, 0.0 hour	74.9 mmHg	Standard Deviation 9.99
Valsartan - HTN Cohort	Supine Diastolic Blood Pressure	Day 1, 12.0 hours post dose	75.7 mmHg	Standard Deviation 8.81

Secondary

Supine Pulse Rate

Pulse rate measurements were taken.

Time frame: 0, 0.5, 1, 2, 4, 8 and 12 hours post dose on day 1; day 2; 0, 0.5, 1, 2, 4, 8 and 12 hours post dose on day 7

Population: The Pharmacodynamic (PD) analysis set, which included all participants who had no major protocol deviation with impact on PD data, were included in the analysis.

Arm	Measure	Group	Value (MEAN)	Dispersion
LCZ696 - Heart Failure (HF) Cohort	Supine Pulse Rate	Day 1, 0.0 hour	56.8 BPM	Standard Deviation 8.89
LCZ696 - Heart Failure (HF) Cohort	Supine Pulse Rate	Day 1, 12.0 hours post dose	61.1 BPM	Standard Deviation 13.36
LCZ696 - Heart Failure (HF) Cohort	Supine Pulse Rate	Day 7, 1.0 hour post dose	63.3 BPM	Standard Deviation 13.21
LCZ696 - Heart Failure (HF) Cohort	Supine Pulse Rate	Day 7, 0.0 hour post dose	63.0 BPM	Standard Deviation 11.97
LCZ696 - Heart Failure (HF) Cohort	Supine Pulse Rate	Day 7, 0.5 hour post dose	65.0 BPM	Standard Deviation 12.63
LCZ696 - Heart Failure (HF) Cohort	Supine Pulse Rate	Day 1, 0.5 hour post dose	61.3 BPM	Standard Deviation 9.34
LCZ696 - Heart Failure (HF) Cohort	Supine Pulse Rate	Day 2	60.1 BPM	Standard Deviation 12.18
LCZ696 - Heart Failure (HF) Cohort	Supine Pulse Rate	Day 7, 4.0 hours post dose	65.7 BPM	Standard Deviation 10.85
LCZ696 - Heart Failure (HF) Cohort	Supine Pulse Rate	Day 1, 1.0 hour post dose	62.4 BPM	Standard Deviation 8.97
LCZ696 - Heart Failure (HF) Cohort	Supine Pulse Rate	Day 7, 12.0 hours post dose	66.7 BPM	Standard Deviation 13.28
LCZ696 - Heart Failure (HF) Cohort	Supine Pulse Rate	Day 1, 2.0 hours post dose	61.0 BPM	Standard Deviation 9.02
LCZ696 - Heart Failure (HF) Cohort	Supine Pulse Rate	Day 7, 8.0 hours post dose	67.1 BPM	Standard Deviation 10.2
LCZ696 - Heart Failure (HF) Cohort	Supine Pulse Rate	Day 7, 2.0 hours post dose	63.9 BPM	Standard Deviation 10.42
LCZ696 - Heart Failure (HF) Cohort	Supine Pulse Rate	Day 1, 4.0 hours post dose	60.0 BPM	Standard Deviation 8.51
LCZ696 - Heart Failure (HF) Cohort	Supine Pulse Rate	Day 1, 8.0 hours post dose	67.6 BPM	Standard Deviation 11.7
Valsartan - HF Cohort	Supine Pulse Rate	Day 1, 8.0 hours post dose	69.1 BPM	Standard Deviation 11.34
Valsartan - HF Cohort	Supine Pulse Rate	Day 1, 1.0 hour post dose	62.7 BPM	Standard Deviation 10.19
Valsartan - HF Cohort	Supine Pulse Rate	Day 2	64.5 BPM	Standard Deviation 11.95
Valsartan - HF Cohort	Supine Pulse Rate	Day 1, 0.0 hour	61.7 BPM	Standard Deviation 14.3
Valsartan - HF Cohort	Supine Pulse Rate	Day 1, 4.0 hours post dose	62.9 BPM	Standard Deviation 13.29
Valsartan - HF Cohort	Supine Pulse Rate	Day 7, 2.0 hours post dose	58.7 BPM	Standard Deviation 11.49
Valsartan - HF Cohort	Supine Pulse Rate	Day 7, 0.0 hour post dose	60.6 BPM	Standard Deviation 12.69
Valsartan - HF Cohort	Supine Pulse Rate	Day 7, 12.0 hours post dose	71.9 BPM	Standard Deviation 17.3
Valsartan - HF Cohort	Supine Pulse Rate	Day 7, 0.5 hour post dose	60.1 BPM	Standard Deviation 12.07
Valsartan - HF Cohort	Supine Pulse Rate	Day 7, 8.0 hours post dose	66.5 BPM	Standard Deviation 11.8
Valsartan - HF Cohort	Supine Pulse Rate	Day 7, 4.0 hours post dose	60.7 BPM	Standard Deviation 11.34
Valsartan - HF Cohort	Supine Pulse Rate	Day 1, 2.0 hours post dose	64.3 BPM	Standard Deviation 12.39
Valsartan - HF Cohort	Supine Pulse Rate	Day 1, 0.5 hour post dose	60.7 BPM	Standard Deviation 10.45
Valsartan - HF Cohort	Supine Pulse Rate	Day 1, 12.0 hours post dose	62.8 BPM	Standard Deviation 10.83
Valsartan - HF Cohort	Supine Pulse Rate	Day 7, 1.0 hour post dose	61.6 BPM	Standard Deviation 11.7
LCZ696 - Hypertension (HTN) Cohort	Supine Pulse Rate	Day 7, 1.0 hour post dose	62.3 BPM	Standard Deviation 5.87
LCZ696 - Hypertension (HTN) Cohort	Supine Pulse Rate	Day 1, 12.0 hours post dose	73.7 BPM	Standard Deviation 13.52
LCZ696 - Hypertension (HTN) Cohort	Supine Pulse Rate	Day 1, 0.0 hour	65.7 BPM	Standard Deviation 9.26
LCZ696 - Hypertension (HTN) Cohort	Supine Pulse Rate	Day 1, 0.5 hour post dose	64.1 BPM	Standard Deviation 8.59
LCZ696 - Hypertension (HTN) Cohort	Supine Pulse Rate	Day 1, 1.0 hour post dose	64.2 BPM	Standard Deviation 7.49
LCZ696 - Hypertension (HTN) Cohort	Supine Pulse Rate	Day 1, 2.0 hours post dose	65.6 BPM	Standard Deviation 8.28
LCZ696 - Hypertension (HTN) Cohort	Supine Pulse Rate	Day 1, 4.0 hours post dose	64.0 BPM	Standard Deviation 6.51
LCZ696 - Hypertension (HTN) Cohort	Supine Pulse Rate	Day 1, 8.0 hours post dose	73.9 BPM	Standard Deviation 10.2
LCZ696 - Hypertension (HTN) Cohort	Supine Pulse Rate	Day 2	71.3 BPM	Standard Deviation 10.58
LCZ696 - Hypertension (HTN) Cohort	Supine Pulse Rate	Day 7, 0.0 hour post dose	62.9 BPM	Standard Deviation 5.54
LCZ696 - Hypertension (HTN) Cohort	Supine Pulse Rate	Day 7, 0.5 hour post dose	63.0 BPM	Standard Deviation 4.36
LCZ696 - Hypertension (HTN) Cohort	Supine Pulse Rate	Day 7, 2.0 hours post dose	61.2 BPM	Standard Deviation 6.17
LCZ696 - Hypertension (HTN) Cohort	Supine Pulse Rate	Day 7, 4.0 hours post dose	62.9 BPM	Standard Deviation 6.45
LCZ696 - Hypertension (HTN) Cohort	Supine Pulse Rate	Day 7, 8.0 hours post dose	66.3 BPM	Standard Deviation 7.34
LCZ696 - Hypertension (HTN) Cohort	Supine Pulse Rate	Day 7, 12.0 hours post dose	66.2 BPM	Standard Deviation 6.97
Valsartan - HTN Cohort	Supine Pulse Rate	Day 1, 4.0 hours post dose	65.3 BPM	Standard Deviation 9.65
Valsartan - HTN Cohort	Supine Pulse Rate	Day 7, 1.0 hour post dose	61.6 BPM	Standard Deviation 7.7
Valsartan - HTN Cohort	Supine Pulse Rate	Day 1, 2.0 hours post dose	63.2 BPM	Standard Deviation 8.89
Valsartan - HTN Cohort	Supine Pulse Rate	Day 1, 1.0 hour post dose	64.0 BPM	Standard Deviation 10.39
Valsartan - HTN Cohort	Supine Pulse Rate	Day 7, 4.0 hours post dose	62.7 BPM	Standard Deviation 9.2
Valsartan - HTN Cohort	Supine Pulse Rate	Day 7, 2.0 hours post dose	63.6 BPM	Standard Deviation 9.16
Valsartan - HTN Cohort	Supine Pulse Rate	Day 1, 0.5 hour post dose	63.4 BPM	Standard Deviation 9.29
Valsartan - HTN Cohort	Supine Pulse Rate	Day 1, 0.0 hour	65.5 BPM	Standard Deviation 8.44
Valsartan - HTN Cohort	Supine Pulse Rate	Day 1, 12.0 hours post dose	65.4 BPM	Standard Deviation 9.68
Valsartan - HTN Cohort	Supine Pulse Rate	Day 7, 12.0 hours post dose	67.1 BPM	Standard Deviation 11.1
Valsartan - HTN Cohort	Supine Pulse Rate	Day 7, 0.0 hour post dose	62.8 BPM	Standard Deviation 8.16
Valsartan - HTN Cohort	Supine Pulse Rate	Day 7, 8.0 hours post dose	64.8 BPM	Standard Deviation 10.83
Valsartan - HTN Cohort	Supine Pulse Rate	Day 7, 0.5 hour post dose	61.8 BPM	Standard Deviation 9.35
Valsartan - HTN Cohort	Supine Pulse Rate	Day 2	66.5 BPM	Standard Deviation 9.2
Valsartan - HTN Cohort	Supine Pulse Rate	Day 1, 8.0 hours post dose	67.5 BPM	Standard Deviation 10.09

Secondary

Supine Systolic Blood Pressure

Systolic blood pressure measurements were taken.

Time frame: 0, 0.5, 1, 2, 4, 8 and 12 hours post dose on day 1; day 2; 0, 0.5, 1, 2, 4, 8 and 12 hours post dose on day 7

Population: The Pharmacodynamic (PD) analysis set, which included all participants who had no major protocol deviation with impact on PD data, were included in the analysis.

Arm	Measure	Group	Value (MEAN)	Dispersion
LCZ696 - Heart Failure (HF) Cohort	Supine Systolic Blood Pressure	Day 1, 0.0 hour	114.8 mmHg	Standard Deviation 14.1
LCZ696 - Heart Failure (HF) Cohort	Supine Systolic Blood Pressure	Day 7, 2.0 hours post dose	119.3 mmHg	Standard Deviation 12.7
LCZ696 - Heart Failure (HF) Cohort	Supine Systolic Blood Pressure	Day 7, 0.0 hour	110.5 mmHg	Standard Deviation 10.03
LCZ696 - Heart Failure (HF) Cohort	Supine Systolic Blood Pressure	Day 1, 1.0 hour post dose	123.9 mmHg	Standard Deviation 16.53
LCZ696 - Heart Failure (HF) Cohort	Supine Systolic Blood Pressure	Day 7, 0.5 hour post dose	116.2 mmHg	Standard Deviation 10.93
LCZ696 - Heart Failure (HF) Cohort	Supine Systolic Blood Pressure	Day 7, 1.0 hour post dose	117.9 mmHg	Standard Deviation 10.01
LCZ696 - Heart Failure (HF) Cohort	Supine Systolic Blood Pressure	Day 1, 2.0 hours post dose	125.4 mmHg	Standard Deviation 13.68
LCZ696 - Heart Failure (HF) Cohort	Supine Systolic Blood Pressure	Day 1, 0.5 hour post dose	122.8 mmHg	Standard Deviation 14.36
LCZ696 - Heart Failure (HF) Cohort	Supine Systolic Blood Pressure	Day 7, 8.0 hours post dose	111.3 mmHg	Standard Deviation 12.52
LCZ696 - Heart Failure (HF) Cohort	Supine Systolic Blood Pressure	Day 1, 4.0 hours post dose	133.1 mmHg	Standard Deviation 18.65
LCZ696 - Heart Failure (HF) Cohort	Supine Systolic Blood Pressure	Day 1, 8.0 hours post dose	113.6 mmHg	Standard Deviation 13.29
LCZ696 - Heart Failure (HF) Cohort	Supine Systolic Blood Pressure	Day 7, 4.0 hours post dose	120.6 mmHg	Standard Deviation 11.71
LCZ696 - Heart Failure (HF) Cohort	Supine Systolic Blood Pressure	Day 1, 12.0 hours post dose	111.1 mmHg	Standard Deviation 14.75
LCZ696 - Heart Failure (HF) Cohort	Supine Systolic Blood Pressure	Day 7, 12.0 hours post dose	107.9 mmHg	Standard Deviation 16.7
LCZ696 - Heart Failure (HF) Cohort	Supine Systolic Blood Pressure	Day 2	115.8 mmHg	Standard Deviation 9.61
Valsartan - HF Cohort	Supine Systolic Blood Pressure	Day 2	120.9 mmHg	Standard Deviation 18.05
Valsartan - HF Cohort	Supine Systolic Blood Pressure	Day 7, 2.0 hours post dose	127.5 mmHg	Standard Deviation 11.95
Valsartan - HF Cohort	Supine Systolic Blood Pressure	Day 1, 4.0 hours post dose	130.3 mmHg	Standard Deviation 17.14
Valsartan - HF Cohort	Supine Systolic Blood Pressure	Day 7, 0.0 hour	115.9 mmHg	Standard Deviation 15.47
Valsartan - HF Cohort	Supine Systolic Blood Pressure	Day 1, 0.5 hour post dose	121.5 mmHg	Standard Deviation 21.78
Valsartan - HF Cohort	Supine Systolic Blood Pressure	Day 7, 1.0 hour post dose	124.8 mmHg	Standard Deviation 12.43
Valsartan - HF Cohort	Supine Systolic Blood Pressure	Day 7, 4.0 hours post dose	128.9 mmHg	Standard Deviation 13.13
Valsartan - HF Cohort	Supine Systolic Blood Pressure	Day 7, 0.5 hour post dose	122.9 mmHg	Standard Deviation 11.78
Valsartan - HF Cohort	Supine Systolic Blood Pressure	Day 1, 1.0 hour post dose	122.2 mmHg	Standard Deviation 19.2
Valsartan - HF Cohort	Supine Systolic Blood Pressure	Day 1, 12.0 hours post dose	114.8 mmHg	Standard Deviation 17.85
Valsartan - HF Cohort	Supine Systolic Blood Pressure	Day 7, 12.0 hours post dose	116.5 mmHg	Standard Deviation 14.85
Valsartan - HF Cohort	Supine Systolic Blood Pressure	Day 7, 8.0 hours post dose	119.3 mmHg	Standard Deviation 10.44
Valsartan - HF Cohort	Supine Systolic Blood Pressure	Day 1, 8.0 hours post dose	120.9 mmHg	Standard Deviation 16.85
Valsartan - HF Cohort	Supine Systolic Blood Pressure	Day 1, 2.0 hours post dose	127.2 mmHg	Standard Deviation 16.71
Valsartan - HF Cohort	Supine Systolic Blood Pressure	Day 1, 0.0 hour	127.0 mmHg	Standard Deviation 16.62
LCZ696 - Hypertension (HTN) Cohort	Supine Systolic Blood Pressure	Day 2	125.4 mmHg	Standard Deviation 12.66
LCZ696 - Hypertension (HTN) Cohort	Supine Systolic Blood Pressure	Day 1, 0.0 hour	136.1 mmHg	Standard Deviation 18.8
LCZ696 - Hypertension (HTN) Cohort	Supine Systolic Blood Pressure	Day 1, 0.5 hour post dose	132.9 mmHg	Standard Deviation 19.52
LCZ696 - Hypertension (HTN) Cohort	Supine Systolic Blood Pressure	Day 1, 1.0 hour post dose	134.1 mmHg	Standard Deviation 18.57
LCZ696 - Hypertension (HTN) Cohort	Supine Systolic Blood Pressure	Day 1, 2.0 hours post dose	134.2 mmHg	Standard Deviation 19.85
LCZ696 - Hypertension (HTN) Cohort	Supine Systolic Blood Pressure	Day 1, 4.0 hours post dose	140.7 mmHg	Standard Deviation 20.67
LCZ696 - Hypertension (HTN) Cohort	Supine Systolic Blood Pressure	Day 1, 8.0 hours post dose	127.3 mmHg	Standard Deviation 17.39
LCZ696 - Hypertension (HTN) Cohort	Supine Systolic Blood Pressure	Day 1, 12.0 hours post dose	127.4 mmHg	Standard Deviation 13.92
LCZ696 - Hypertension (HTN) Cohort	Supine Systolic Blood Pressure	Day 7, 0.0 hour	128.9 mmHg	Standard Deviation 14.83
LCZ696 - Hypertension (HTN) Cohort	Supine Systolic Blood Pressure	Day 7, 0.5 hour post dose	127.4 mmHg	Standard Deviation 16.26
LCZ696 - Hypertension (HTN) Cohort	Supine Systolic Blood Pressure	Day 7, 1.0 hour post dose	127.4 mmHg	Standard Deviation 17.46
LCZ696 - Hypertension (HTN) Cohort	Supine Systolic Blood Pressure	Day 7, 2.0 hours post dose	128.6 mmHg	Standard Deviation 19.35
LCZ696 - Hypertension (HTN) Cohort	Supine Systolic Blood Pressure	Day 7, 4.0 hours post dose	130.5 mmHg	Standard Deviation 18.15
LCZ696 - Hypertension (HTN) Cohort	Supine Systolic Blood Pressure	Day 7, 8.0 hours post dose	123.1 mmHg	Standard Deviation 12.72
LCZ696 - Hypertension (HTN) Cohort	Supine Systolic Blood Pressure	Day 7, 12.0 hours post dose	120.3 mmHg	Standard Deviation 12.6
Valsartan - HTN Cohort	Supine Systolic Blood Pressure	Day 1, 12.0 hours post dose	134.1 mmHg	Standard Deviation 14.64
Valsartan - HTN Cohort	Supine Systolic Blood Pressure	Day 1, 0.5 hour post dose	132.5 mmHg	Standard Deviation 17.85
Valsartan - HTN Cohort	Supine Systolic Blood Pressure	Day 7, 2.0 hours post dose	140.7 mmHg	Standard Deviation 15.89
Valsartan - HTN Cohort	Supine Systolic Blood Pressure	Day 1, 8.0 hours post dose	132.2 mmHg	Standard Deviation 11.4
Valsartan - HTN Cohort	Supine Systolic Blood Pressure	Day 1, 4.0 hours post dose	142.1 mmHg	Standard Deviation 17.93
Valsartan - HTN Cohort	Supine Systolic Blood Pressure	Day 1, 0.0 hour	133.2 mmHg	Standard Deviation 14.79
Valsartan - HTN Cohort	Supine Systolic Blood Pressure	Day 7, 4.0 hours post dose	134.9 mmHg	Standard Deviation 13.2
Valsartan - HTN Cohort	Supine Systolic Blood Pressure	Day 1, 2.0 hours post dose	132.6 mmHg	Standard Deviation 17.47
Valsartan - HTN Cohort	Supine Systolic Blood Pressure	Day 1, 1.0 hour post dose	133.2 mmHg	Standard Deviation 15.22
Valsartan - HTN Cohort	Supine Systolic Blood Pressure	Day 7, 12.0 hours post dose	131.9 mmHg	Standard Deviation 18.71
Valsartan - HTN Cohort	Supine Systolic Blood Pressure	Day 7, 0.5 hour post dose	130.9 mmHg	Standard Deviation 15.06
Valsartan - HTN Cohort	Supine Systolic Blood Pressure	Day 7, 0.0 hour	128.8 mmHg	Standard Deviation 13.76
Valsartan - HTN Cohort	Supine Systolic Blood Pressure	Day 7, 8.0 hours post dose	130.0 mmHg	Standard Deviation 15.88
Valsartan - HTN Cohort	Supine Systolic Blood Pressure	Day 7, 1.0 hour post dose	130.9 mmHg	Standard Deviation 15.47
Valsartan - HTN Cohort	Supine Systolic Blood Pressure	Day 2	128.9 mmHg	Standard Deviation 13.99

Secondary

Urinary Cyclic Guanosine Monophosphate (cGMP) Excretion Over 24 Hours

cGMP was analyzed at a central laboratory. The measure type used for this OM was Geometric LSM.

Time frame: day 1, day 6, day 7

Population: The Pharmacodynamic (PD) analysis set, which included all participants who had no major protocol deviation with impact on PD data, were included in the analysis.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)
LCZ696 - Heart Failure (HF) Cohort	Urinary Cyclic Guanosine Monophosphate (cGMP) Excretion Over 24 Hours	Day 1	1851.79 nmol/24 hours
LCZ696 - Heart Failure (HF) Cohort	Urinary Cyclic Guanosine Monophosphate (cGMP) Excretion Over 24 Hours	Day 7	1571.02 nmol/24 hours
LCZ696 - Heart Failure (HF) Cohort	Urinary Cyclic Guanosine Monophosphate (cGMP) Excretion Over 24 Hours	Day 6	1467.67 nmol/24 hours
Valsartan - HF Cohort	Urinary Cyclic Guanosine Monophosphate (cGMP) Excretion Over 24 Hours	Day 1	884.99 nmol/24 hours
Valsartan - HF Cohort	Urinary Cyclic Guanosine Monophosphate (cGMP) Excretion Over 24 Hours	Day 7	859.07 nmol/24 hours
Valsartan - HF Cohort	Urinary Cyclic Guanosine Monophosphate (cGMP) Excretion Over 24 Hours	Day 6	865.62 nmol/24 hours
LCZ696 - Hypertension (HTN) Cohort	Urinary Cyclic Guanosine Monophosphate (cGMP) Excretion Over 24 Hours	Day 6	863.32 nmol/24 hours
LCZ696 - Hypertension (HTN) Cohort	Urinary Cyclic Guanosine Monophosphate (cGMP) Excretion Over 24 Hours	Day 1	1085.76 nmol/24 hours
LCZ696 - Hypertension (HTN) Cohort	Urinary Cyclic Guanosine Monophosphate (cGMP) Excretion Over 24 Hours	Day 7	1107.04 nmol/24 hours
Valsartan - HTN Cohort	Urinary Cyclic Guanosine Monophosphate (cGMP) Excretion Over 24 Hours	Day 1	557.53 nmol/24 hours
Valsartan - HTN Cohort	Urinary Cyclic Guanosine Monophosphate (cGMP) Excretion Over 24 Hours	Day 7	603.90 nmol/24 hours
Valsartan - HTN Cohort	Urinary Cyclic Guanosine Monophosphate (cGMP) Excretion Over 24 Hours	Day 6	562.11 nmol/24 hours

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

Sodium Excretion of LCZ696 in Patients With Hypertension; Heart Failure and Healthy Volunteers

Conditions

Keywords

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

24-hour Urinary Sodium Excretion

Cumulative 7-day Urinary Sodium Excretion

24-hour Diuresis

7-day Cumulative Diuresis

Glomerular Filtration Rate (GFR) Over Time

Percent Change From Baseline in Aldosterone Biomarker

Percent Change From Baseline in Blood Plasma Creatinine

Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker

Percent Change From Baseline in C-terminal-proendothelin-1 (CT-proET-1) Biomarker

Percent Change From Baseline in C-type Natriuretic Peptide (proCNP) Biomarker

Percent Change From Baseline in Mid-regional Pro-adrenomedullin (MR-proADM) Biomarker

Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker

Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker

Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)

Renal Blood Flow (RBF) Over Time

Supine Diastolic Blood Pressure

Supine Pulse Rate

Supine Systolic Blood Pressure

Urinary Cyclic Guanosine Monophosphate (cGMP) Excretion Over 24 Hours