Pharmacokinetics of LCZ696 in Subjects With Mild and Moderate Renal Impairment Compared to Healthy Subjects With Normal Renal Function

An Open Label, Parallel-group Study to Determine Multiple Dose Pharmacokinetics of LCZ696 and Its Metabolites in Subjects With Mild and Moderate Renal Impairment Compared to Matched Healthy Subjects With Normal Renal Function

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01569815

Enrollment

Registered

2012-04-03

Start date

2009-02-28

Completion date

2014-08-31

Last updated

2015-10-19

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

Conditions

Mild and Moderate Renal Impairment

Keywords

Renal Impairment,, LCZ696

Brief summary

The purpose of this study is to determine the multiple dose pharmacokinetics of LCZ696 and its metabolites in subjects with mild to moderate renal impairment and to evaluate the safety of LCZ696 in this population.

Interventions

DRUGLCZ696

LCZ696 400 mg once daily

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

BASIC_SCIENCE

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Yes

Inclusion criteria

1. Male, and female subjects of non-child bearing potential, 2. Subjects were to weigh at least 50 kg to participate in the study, 3. and body mass index \< 40 kg/m2 4. Subjects were able to communicate well with the investigator, to understand and comply with the requirements of the study; 5. Subjects were able to understand and sign the written informed consent; For renal insufficient subjects: 1. stable renal disease without evidence of renal progressive * mild renal function: calculated CrCl of 50-≤80 mL/min * moderate renal function: calculated CrCl of 30-\<50 mL/min 2. Vital signs: * oral body temperature between 35.0-37.8 °C * systolic blood pressure, 95-180 mm Hg * diastolic blood pressure, 60-110 mm Hg * pulse rate, 54-95 bpm For healthy subjects only 1. A serum creatinine with a calculated CrCl of \>80 mL/min 2. Vital signs: * oral body temperature between 35.0-37.2 °C * systolic blood pressure, 95-140 mm Hg * diastolic blood pressure, 60-100 mm Hg * pulse rate, 45-90 bpm

Exclusion criteria

1. Current use of ACE inhibitors, valsartan, and drugs that were known as CYP2C9 substrates, potassium-sparing diuretics; 2. Smokers; 3. History of renal transplant at any time in the past and on immunosuppressant therapy; 4. Dialysis patients; 5. Medical history of clinically significant ECG abnormalities or a family history of a prolonged QT-interval syndrome; 6. Any surgical or medical condition which may significantly alter the absorption, distribution, metabolism or excretion of any drug substance; Other protocol defined inclusion/

Design outcomes

Primary

Measure	Time frame	Description
Amount of Drug Excreted Into the Urine From Time Zero to 24-hours Post-dose (Ae0-24) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	Day 1 and Day 5	Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril)
Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	Day 1 and day 5	Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril)
Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	Day 1, day 5	Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril)
Area Under the Concentration-time Curve (AUC0-24) From Time Zero to 24- Hour Post-dose (Day 1), and After Multiple Dose Administration (Day 5)	Day 1 and day 5	Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril)
Elimination Half-life (t1/2) After Multiple Dose (Day 5) Administration	Day 5	Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril)
Systemic Clearance From Plasma Following Extravascular Administration (CL/F) After Multiple Dose Administration (Day 5)	Day 5	Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril)
Accumulation Ratio (Racc) After Multiple Dose Administration (Day 5)	Day 5	Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril)
Renal Clearance From Plasma (CLr) After Multiple Dose Administration (Day 5)	Day 5	Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril)

Secondary

Measure	Time frame	Description
Change in Mean 24-hours Sodium Clearance From Baseline to Day 7	From baseline to Day 7	Sodium clearance will be measured in urine from baseline until Day 7

Countries

Germany, Russia, Serbia

Participant flow

Participants by arm

Arm	Count
Mild Renal Impaired Subjects LCZ696 400 mg once daily for 5 days	8
Mild Renal Impaired Matched Healthy Subjects LCZ696 400 mg once daily for 5 days	8
Moderate Renal Impaired Subjects LCZ696 400 mg once daily for 5 days	8
Moderate Renal Impaired Matched Healthy Subjects LCZ696 400 mg once daily for 5 days	8
Total	32

Baseline characteristics

Characteristic	Mild Renal Impaired Subjects	Total	Moderate Renal Impaired Matched Healthy Subjects	Moderate Renal Impaired Subjects	Mild Renal Impaired Matched Healthy Subjects
Age, Continuous	51.0 years STANDARD_DEVIATION 10.88	52.5 years STANDARD_DEVIATION 9.72	53.9 years STANDARD_DEVIATION 8.95	54.5 years STANDARD_DEVIATION 8.33	50.6 years STANDARD_DEVIATION 11.7
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	8 Participants	32 Participants	8 Participants	8 Participants	8 Participants
Sex: Female, Male Female	1 Participants	8 Participants	3 Participants	3 Participants	1 Participants
Sex: Female, Male Male	7 Participants	24 Participants	5 Participants	5 Participants	7 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	7 / 8	3 / 8	8 / 8	1 / 8	4 / 16
serious Total, serious adverse events	0 / 8	0 / 8	0 / 8	0 / 8	0 / 16

Outcome results

Primary

Accumulation Ratio (Racc) After Multiple Dose Administration (Day 5)

Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril)

Time frame: Day 5

Population: FAS

Arm	Measure	Group	Value (MEAN)	Dispersion
Mild Renal Impaired Subjects	Accumulation Ratio (Racc) After Multiple Dose Administration (Day 5)	VAL489 day 5,multiple dose LCZ696 400 mg Q.D	1.0 Ratio (AUC0-24, day 5)/(AUC0-24, day 1)	Standard Deviation 0.4
Mild Renal Impaired Subjects	Accumulation Ratio (Racc) After Multiple Dose Administration (Day 5)	AHU377 day 5, multiple dose of LCZ696 400 mg Q.D	1.0 Ratio (AUC0-24, day 5)/(AUC0-24, day 1)	Standard Deviation 0.1
Mild Renal Impaired Subjects	Accumulation Ratio (Racc) After Multiple Dose Administration (Day 5)	LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D	1.64 Ratio (AUC0-24, day 5)/(AUC0-24, day 1)	Standard Deviation 0.27
Mild Renal Impaired Matched Healthy Subjects	Accumulation Ratio (Racc) After Multiple Dose Administration (Day 5)	AHU377 day 5, multiple dose of LCZ696 400 mg Q.D	1.0 Ratio (AUC0-24, day 5)/(AUC0-24, day 1)	Standard Deviation 0.2
Mild Renal Impaired Matched Healthy Subjects	Accumulation Ratio (Racc) After Multiple Dose Administration (Day 5)	VAL489 day 5,multiple dose LCZ696 400 mg Q.D	0.9 Ratio (AUC0-24, day 5)/(AUC0-24, day 1)	Standard Deviation 0.2
Mild Renal Impaired Matched Healthy Subjects	Accumulation Ratio (Racc) After Multiple Dose Administration (Day 5)	LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D	1.19 Ratio (AUC0-24, day 5)/(AUC0-24, day 1)	Standard Deviation 0.09
Moderate Renal Impaired Subjects	Accumulation Ratio (Racc) After Multiple Dose Administration (Day 5)	VAL489 day 5,multiple dose LCZ696 400 mg Q.D	1.3 Ratio (AUC0-24, day 5)/(AUC0-24, day 1)	Standard Deviation 0.6
Moderate Renal Impaired Subjects	Accumulation Ratio (Racc) After Multiple Dose Administration (Day 5)	AHU377 day 5, multiple dose of LCZ696 400 mg Q.D	1.0 Ratio (AUC0-24, day 5)/(AUC0-24, day 1)	Standard Deviation 0.2
Moderate Renal Impaired Subjects	Accumulation Ratio (Racc) After Multiple Dose Administration (Day 5)	LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D	1.6 Ratio (AUC0-24, day 5)/(AUC0-24, day 1)	Standard Deviation 0.3
Moderate Renal Impaired Matched Healthy Subjects	Accumulation Ratio (Racc) After Multiple Dose Administration (Day 5)	VAL489 day 5,multiple dose LCZ696 400 mg Q.D	1.1 Ratio (AUC0-24, day 5)/(AUC0-24, day 1)	Standard Deviation 0.5
Moderate Renal Impaired Matched Healthy Subjects	Accumulation Ratio (Racc) After Multiple Dose Administration (Day 5)	LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D	1.2 Ratio (AUC0-24, day 5)/(AUC0-24, day 1)	Standard Deviation 0.1
Moderate Renal Impaired Matched Healthy Subjects	Accumulation Ratio (Racc) After Multiple Dose Administration (Day 5)	AHU377 day 5, multiple dose of LCZ696 400 mg Q.D	1.0 Ratio (AUC0-24, day 5)/(AUC0-24, day 1)	Standard Deviation 0.2

Primary

Amount of Drug Excreted Into the Urine From Time Zero to 24-hours Post-dose (Ae0-24) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)

Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril)

Time frame: Day 1 and Day 5

Arm	Measure	Group	Value (MEAN)	Dispersion
Mild Renal Impaired Subjects	Amount of Drug Excreted Into the Urine From Time Zero to 24-hours Post-dose (Ae0-24) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	AHU377 day 1, single dose of LCZ696 400 mg	360.2 ug	Standard Deviation 99.1
Mild Renal Impaired Subjects	Amount of Drug Excreted Into the Urine From Time Zero to 24-hours Post-dose (Ae0-24) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	AHU377 day 5, multiple dose of LCZ696 400 mg Q.D	426.2 ug	Standard Deviation 120.3
Mild Renal Impaired Subjects	Amount of Drug Excreted Into the Urine From Time Zero to 24-hours Post-dose (Ae0-24) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	LBQ657 day 1, single dose of LCZ696 400 mg	52687 ug	Standard Deviation 17107
Mild Renal Impaired Subjects	Amount of Drug Excreted Into the Urine From Time Zero to 24-hours Post-dose (Ae0-24) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	VAL489 day 1, single dose of LCZ696 400 mg	7206 ug	Standard Deviation 3082
Mild Renal Impaired Subjects	Amount of Drug Excreted Into the Urine From Time Zero to 24-hours Post-dose (Ae0-24) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	VAL489 day 5,multiple dose LCZ696 400 mg Q.D	6849 ug	Standard Deviation 3852
Mild Renal Impaired Subjects	Amount of Drug Excreted Into the Urine From Time Zero to 24-hours Post-dose (Ae0-24) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D	87768 ug	Standard Deviation 21278
Mild Renal Impaired Matched Healthy Subjects	Amount of Drug Excreted Into the Urine From Time Zero to 24-hours Post-dose (Ae0-24) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	AHU377 day 1, single dose of LCZ696 400 mg	1560 ug	Standard Deviation 1294
Mild Renal Impaired Matched Healthy Subjects	Amount of Drug Excreted Into the Urine From Time Zero to 24-hours Post-dose (Ae0-24) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	AHU377 day 5, multiple dose of LCZ696 400 mg Q.D	734.5 ug	Standard Deviation 662.8
Mild Renal Impaired Matched Healthy Subjects	Amount of Drug Excreted Into the Urine From Time Zero to 24-hours Post-dose (Ae0-24) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	VAL489 day 1, single dose of LCZ696 400 mg	13792 ug	Standard Deviation 5250
Mild Renal Impaired Matched Healthy Subjects	Amount of Drug Excreted Into the Urine From Time Zero to 24-hours Post-dose (Ae0-24) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D	83254 ug	Standard Deviation 35800
Mild Renal Impaired Matched Healthy Subjects	Amount of Drug Excreted Into the Urine From Time Zero to 24-hours Post-dose (Ae0-24) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	LBQ657 day 1, single dose of LCZ696 400 mg	68397 ug	Standard Deviation 17535
Mild Renal Impaired Matched Healthy Subjects	Amount of Drug Excreted Into the Urine From Time Zero to 24-hours Post-dose (Ae0-24) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	VAL489 day 5,multiple dose LCZ696 400 mg Q.D	11625 ug	Standard Deviation 6186
Moderate Renal Impaired Subjects	Amount of Drug Excreted Into the Urine From Time Zero to 24-hours Post-dose (Ae0-24) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	AHU377 day 5, multiple dose of LCZ696 400 mg Q.D	316.8 ug	Standard Deviation 362.9
Moderate Renal Impaired Subjects	Amount of Drug Excreted Into the Urine From Time Zero to 24-hours Post-dose (Ae0-24) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	AHU377 day 1, single dose of LCZ696 400 mg	419.4 ug	Standard Deviation 351.1
Moderate Renal Impaired Subjects	Amount of Drug Excreted Into the Urine From Time Zero to 24-hours Post-dose (Ae0-24) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	VAL489 day 5,multiple dose LCZ696 400 mg Q.D	3713 ug	Standard Deviation 1843
Moderate Renal Impaired Subjects	Amount of Drug Excreted Into the Urine From Time Zero to 24-hours Post-dose (Ae0-24) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D	43952 ug	Standard Deviation 20678
Moderate Renal Impaired Subjects	Amount of Drug Excreted Into the Urine From Time Zero to 24-hours Post-dose (Ae0-24) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	LBQ657 day 1, single dose of LCZ696 400 mg	29653 ug	Standard Deviation 11767
Moderate Renal Impaired Subjects	Amount of Drug Excreted Into the Urine From Time Zero to 24-hours Post-dose (Ae0-24) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	VAL489 day 1, single dose of LCZ696 400 mg	4156 ug	Standard Deviation 2634
Moderate Renal Impaired Matched Healthy Subjects	Amount of Drug Excreted Into the Urine From Time Zero to 24-hours Post-dose (Ae0-24) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	AHU377 day 5, multiple dose of LCZ696 400 mg Q.D	790.8 ug	Standard Deviation 872.6
Moderate Renal Impaired Matched Healthy Subjects	Amount of Drug Excreted Into the Urine From Time Zero to 24-hours Post-dose (Ae0-24) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	LBQ657 day 1, single dose of LCZ696 400 mg	75699 ug	Standard Deviation 15612
Moderate Renal Impaired Matched Healthy Subjects	Amount of Drug Excreted Into the Urine From Time Zero to 24-hours Post-dose (Ae0-24) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D	92113 ug	Standard Deviation 22572
Moderate Renal Impaired Matched Healthy Subjects	Amount of Drug Excreted Into the Urine From Time Zero to 24-hours Post-dose (Ae0-24) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	VAL489 day 1, single dose of LCZ696 400 mg	16902 ug	Standard Deviation 4628
Moderate Renal Impaired Matched Healthy Subjects	Amount of Drug Excreted Into the Urine From Time Zero to 24-hours Post-dose (Ae0-24) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	AHU377 day 1, single dose of LCZ696 400 mg	2083 ug	Standard Deviation 2496
Moderate Renal Impaired Matched Healthy Subjects	Amount of Drug Excreted Into the Urine From Time Zero to 24-hours Post-dose (Ae0-24) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	VAL489 day 5,multiple dose LCZ696 400 mg Q.D	16385 ug	Standard Deviation 8260

Primary

Area Under the Concentration-time Curve (AUC0-24) From Time Zero to 24- Hour Post-dose (Day 1), and After Multiple Dose Administration (Day 5)

Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril)

Time frame: Day 1 and day 5

Population: FAS

Arm	Measure	Group	Value (MEAN)	Dispersion
Mild Renal Impaired Subjects	Area Under the Concentration-time Curve (AUC0-24) From Time Zero to 24- Hour Post-dose (Day 1), and After Multiple Dose Administration (Day 5)	AHU377 day 1, single dose of LCZ696 400 mg	5679 ng*hr/mL	Standard Deviation 1864
Mild Renal Impaired Subjects	Area Under the Concentration-time Curve (AUC0-24) From Time Zero to 24- Hour Post-dose (Day 1), and After Multiple Dose Administration (Day 5)	AHU377 day 5, multiple doses of LCZ696 400 mg Q.D	5656 ng*hr/mL	Standard Deviation 1859
Mild Renal Impaired Subjects	Area Under the Concentration-time Curve (AUC0-24) From Time Zero to 24- Hour Post-dose (Day 1), and After Multiple Dose Administration (Day 5)	VAL489 day 5,multiple dose LCZ696 400 mg Q.D	59223 ng*hr/mL	Standard Deviation 50669
Mild Renal Impaired Subjects	Area Under the Concentration-time Curve (AUC0-24) From Time Zero to 24- Hour Post-dose (Day 1), and After Multiple Dose Administration (Day 5)	LBQ657 day 1, single dose of LCZ696 400 mg	226159 ng*hr/mL	Standard Deviation 49810
Mild Renal Impaired Subjects	Area Under the Concentration-time Curve (AUC0-24) From Time Zero to 24- Hour Post-dose (Day 1), and After Multiple Dose Administration (Day 5)	LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D.	371331 ng*hr/mL	Standard Deviation 99259
Mild Renal Impaired Subjects	Area Under the Concentration-time Curve (AUC0-24) From Time Zero to 24- Hour Post-dose (Day 1), and After Multiple Dose Administration (Day 5)	VAL489 day 1, single dose of LCZ696 400 mg	62411 ng*hr/mL	Standard Deviation 43846
Mild Renal Impaired Matched Healthy Subjects	Area Under the Concentration-time Curve (AUC0-24) From Time Zero to 24- Hour Post-dose (Day 1), and After Multiple Dose Administration (Day 5)	AHU377 day 1, single dose of LCZ696 400 mg	5396 ng*hr/mL	Standard Deviation 1197
Mild Renal Impaired Matched Healthy Subjects	Area Under the Concentration-time Curve (AUC0-24) From Time Zero to 24- Hour Post-dose (Day 1), and After Multiple Dose Administration (Day 5)	LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D.	172335 ng*hr/mL	Standard Deviation 21925
Mild Renal Impaired Matched Healthy Subjects	Area Under the Concentration-time Curve (AUC0-24) From Time Zero to 24- Hour Post-dose (Day 1), and After Multiple Dose Administration (Day 5)	VAL489 day 5,multiple dose LCZ696 400 mg Q.D	39517 ng*hr/mL	Standard Deviation 17227
Mild Renal Impaired Matched Healthy Subjects	Area Under the Concentration-time Curve (AUC0-24) From Time Zero to 24- Hour Post-dose (Day 1), and After Multiple Dose Administration (Day 5)	AHU377 day 5, multiple doses of LCZ696 400 mg Q.D	5221 ng*hr/mL	Standard Deviation 1162
Mild Renal Impaired Matched Healthy Subjects	Area Under the Concentration-time Curve (AUC0-24) From Time Zero to 24- Hour Post-dose (Day 1), and After Multiple Dose Administration (Day 5)	VAL489 day 1, single dose of LCZ696 400 mg	40658 ng*hr/mL	Standard Deviation 11401
Mild Renal Impaired Matched Healthy Subjects	Area Under the Concentration-time Curve (AUC0-24) From Time Zero to 24- Hour Post-dose (Day 1), and After Multiple Dose Administration (Day 5)	LBQ657 day 1, single dose of LCZ696 400 mg	144500 ng*hr/mL	Standard Deviation 15533
Moderate Renal Impaired Subjects	Area Under the Concentration-time Curve (AUC0-24) From Time Zero to 24- Hour Post-dose (Day 1), and After Multiple Dose Administration (Day 5)	VAL489 day 5,multiple dose LCZ696 400 mg Q.D	51777 ng*hr/mL	Standard Deviation 18967
Moderate Renal Impaired Subjects	Area Under the Concentration-time Curve (AUC0-24) From Time Zero to 24- Hour Post-dose (Day 1), and After Multiple Dose Administration (Day 5)	LBQ657 day 1, single dose of LCZ696 400 mg	262422 ng*hr/mL	Standard Deviation 52115
Moderate Renal Impaired Subjects	Area Under the Concentration-time Curve (AUC0-24) From Time Zero to 24- Hour Post-dose (Day 1), and After Multiple Dose Administration (Day 5)	VAL489 day 1, single dose of LCZ696 400 mg	47135 ng*hr/mL	Standard Deviation 21560
Moderate Renal Impaired Subjects	Area Under the Concentration-time Curve (AUC0-24) From Time Zero to 24- Hour Post-dose (Day 1), and After Multiple Dose Administration (Day 5)	AHU377 day 5, multiple doses of LCZ696 400 mg Q.D	5283 ng*hr/mL	Standard Deviation 2267
Moderate Renal Impaired Subjects	Area Under the Concentration-time Curve (AUC0-24) From Time Zero to 24- Hour Post-dose (Day 1), and After Multiple Dose Administration (Day 5)	LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D.	437134 ng*hr/mL	Standard Deviation 146930
Moderate Renal Impaired Subjects	Area Under the Concentration-time Curve (AUC0-24) From Time Zero to 24- Hour Post-dose (Day 1), and After Multiple Dose Administration (Day 5)	AHU377 day 1, single dose of LCZ696 400 mg	5359 ng*hr/mL	Standard Deviation 2287
Moderate Renal Impaired Matched Healthy Subjects	Area Under the Concentration-time Curve (AUC0-24) From Time Zero to 24- Hour Post-dose (Day 1), and After Multiple Dose Administration (Day 5)	LBQ657 day 1, single dose of LCZ696 400 mg	154871 ng*hr/mL	Standard Deviation 31504
Moderate Renal Impaired Matched Healthy Subjects	Area Under the Concentration-time Curve (AUC0-24) From Time Zero to 24- Hour Post-dose (Day 1), and After Multiple Dose Administration (Day 5)	VAL489 day 1, single dose of LCZ696 400 mg	50220 ng*hr/mL	Standard Deviation 19732
Moderate Renal Impaired Matched Healthy Subjects	Area Under the Concentration-time Curve (AUC0-24) From Time Zero to 24- Hour Post-dose (Day 1), and After Multiple Dose Administration (Day 5)	AHU377 day 5, multiple doses of LCZ696 400 mg Q.D	5716 ng*hr/mL	Standard Deviation 1849
Moderate Renal Impaired Matched Healthy Subjects	Area Under the Concentration-time Curve (AUC0-24) From Time Zero to 24- Hour Post-dose (Day 1), and After Multiple Dose Administration (Day 5)	AHU377 day 1, single dose of LCZ696 400 mg	5963 ng*hr/mL	Standard Deviation 2559
Moderate Renal Impaired Matched Healthy Subjects	Area Under the Concentration-time Curve (AUC0-24) From Time Zero to 24- Hour Post-dose (Day 1), and After Multiple Dose Administration (Day 5)	VAL489 day 5,multiple dose LCZ696 400 mg Q.D	56460 ng*hr/mL	Standard Deviation 31412
Moderate Renal Impaired Matched Healthy Subjects	Area Under the Concentration-time Curve (AUC0-24) From Time Zero to 24- Hour Post-dose (Day 1), and After Multiple Dose Administration (Day 5)	LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D.	190598 ng*hr/mL	Standard Deviation 44468

Primary

Elimination Half-life (t1/2) After Multiple Dose (Day 5) Administration

Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril)

Time frame: Day 5

Population: FAS

Arm	Measure	Group	Value (MEAN)	Dispersion
Mild Renal Impaired Subjects	Elimination Half-life (t1/2) After Multiple Dose (Day 5) Administration	AHU377 day 5, multiple doses of LCZ696 400 mg Q.D	1.6 hr	Standard Deviation 0.6
Mild Renal Impaired Subjects	Elimination Half-life (t1/2) After Multiple Dose (Day 5) Administration	VAL489 day 5,multiple dose LCZ696 400 mg Q.D	15.4 hr	Standard Deviation 4.7
Mild Renal Impaired Subjects	Elimination Half-life (t1/2) After Multiple Dose (Day 5) Administration	LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D	21.1 hr	Standard Deviation 8.3
Mild Renal Impaired Matched Healthy Subjects	Elimination Half-life (t1/2) After Multiple Dose (Day 5) Administration	AHU377 day 5, multiple doses of LCZ696 400 mg Q.D	4.7 hr	Standard Deviation 6
Mild Renal Impaired Matched Healthy Subjects	Elimination Half-life (t1/2) After Multiple Dose (Day 5) Administration	VAL489 day 5,multiple dose LCZ696 400 mg Q.D	14.5 hr	Standard Deviation 3.7
Mild Renal Impaired Matched Healthy Subjects	Elimination Half-life (t1/2) After Multiple Dose (Day 5) Administration	LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D	12.6 hr	Standard Deviation 1.7
Moderate Renal Impaired Subjects	Elimination Half-life (t1/2) After Multiple Dose (Day 5) Administration	LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D	23.7 hr	Standard Deviation 5
Moderate Renal Impaired Subjects	Elimination Half-life (t1/2) After Multiple Dose (Day 5) Administration	AHU377 day 5, multiple doses of LCZ696 400 mg Q.D	2.9 hr	Standard Deviation 2.3
Moderate Renal Impaired Subjects	Elimination Half-life (t1/2) After Multiple Dose (Day 5) Administration	VAL489 day 5,multiple dose LCZ696 400 mg Q.D	22.7 hr	Standard Deviation 14.6
Moderate Renal Impaired Matched Healthy Subjects	Elimination Half-life (t1/2) After Multiple Dose (Day 5) Administration	AHU377 day 5, multiple doses of LCZ696 400 mg Q.D	1.8 hr	Standard Deviation 1.2
Moderate Renal Impaired Matched Healthy Subjects	Elimination Half-life (t1/2) After Multiple Dose (Day 5) Administration	VAL489 day 5,multiple dose LCZ696 400 mg Q.D	12.4 hr	Standard Deviation 3
Moderate Renal Impaired Matched Healthy Subjects	Elimination Half-life (t1/2) After Multiple Dose (Day 5) Administration	LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D	12.3 hr	Standard Deviation 2.2

Primary

Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)

Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril)

Time frame: Day 1, day 5

Arm	Measure	Group	Value (MEAN)	Dispersion
Mild Renal Impaired Subjects	Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	AHU377 day 1, single dose of LCZ696 400 mg	4220 ng/mL	Standard Deviation 1514
Mild Renal Impaired Subjects	Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	AHU377 day 5, multiple doses of LCZ696 400 mg Q.D	3904 ng/mL	Standard Deviation 1780
Mild Renal Impaired Subjects	Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	LBQ657 day 1, single dose of LCZ696 400 mg	17575 ng/mL	Standard Deviation 3500
Mild Renal Impaired Subjects	Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	LBQ657 day 5, multiple doses of LCZ696 400 mg Q.D.	27150 ng/mL	Standard Deviation 6449
Mild Renal Impaired Subjects	Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	VAL489 day 1, single dose of LCZ696 400 mg	7208 ng/mL	Standard Deviation 3606
Mild Renal Impaired Subjects	Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	VAL489 day 5,multiple dose LCZ696 400 mg Q.D.	6873 ng/mL	Standard Deviation 4348
Mild Renal Impaired Matched Healthy Subjects	Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	VAL489 day 5,multiple dose LCZ696 400 mg Q.D.	6275 ng/mL	Standard Deviation 2242
Mild Renal Impaired Matched Healthy Subjects	Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	LBQ657 day 5, multiple doses of LCZ696 400 mg Q.D.	16838 ng/mL	Standard Deviation 3063
Mild Renal Impaired Matched Healthy Subjects	Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	AHU377 day 1, single dose of LCZ696 400 mg	3995 ng/mL	Standard Deviation 1368
Mild Renal Impaired Matched Healthy Subjects	Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	LBQ657 day 1, single dose of LCZ696 400 mg	15200 ng/mL	Standard Deviation 2958
Mild Renal Impaired Matched Healthy Subjects	Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	AHU377 day 5, multiple doses of LCZ696 400 mg Q.D	3125 ng/mL	Standard Deviation 1729
Mild Renal Impaired Matched Healthy Subjects	Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	VAL489 day 1, single dose of LCZ696 400 mg	6215 ng/mL	Standard Deviation 1588
Moderate Renal Impaired Subjects	Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	AHU377 day 5, multiple doses of LCZ696 400 mg Q.D	4109 ng/mL	Standard Deviation 1739
Moderate Renal Impaired Subjects	Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	LBQ657 day 1, single dose of LCZ696 400 mg	18175 ng/mL	Standard Deviation 3210
Moderate Renal Impaired Subjects	Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	LBQ657 day 5, multiple doses of LCZ696 400 mg Q.D.	28988 ng/mL	Standard Deviation 7861
Moderate Renal Impaired Subjects	Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	VAL489 day 5,multiple dose LCZ696 400 mg Q.D.	7665 ng/mL	Standard Deviation 2612
Moderate Renal Impaired Subjects	Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	VAL489 day 1, single dose of LCZ696 400 mg	6178 ng/mL	Standard Deviation 2584
Moderate Renal Impaired Subjects	Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	AHU377 day 1, single dose of LCZ696 400 mg	3539 ng/mL	Standard Deviation 1414
Moderate Renal Impaired Matched Healthy Subjects	Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	VAL489 day 1, single dose of LCZ696 400 mg	7981 ng/mL	Standard Deviation 2059
Moderate Renal Impaired Matched Healthy Subjects	Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	VAL489 day 5,multiple dose LCZ696 400 mg Q.D.	8006 ng/mL	Standard Deviation 3895
Moderate Renal Impaired Matched Healthy Subjects	Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	AHU377 day 5, multiple doses of LCZ696 400 mg Q.D	3756 ng/mL	Standard Deviation 1644
Moderate Renal Impaired Matched Healthy Subjects	Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	LBQ657 day 5, multiple doses of LCZ696 400 mg Q.D.	18375 ng/mL	Standard Deviation 3215
Moderate Renal Impaired Matched Healthy Subjects	Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	AHU377 day 1, single dose of LCZ696 400 mg	3743 ng/mL	Standard Deviation 1486
Moderate Renal Impaired Matched Healthy Subjects	Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	LBQ657 day 1, single dose of LCZ696 400 mg	16000 ng/mL	Standard Deviation 2451

Primary

Renal Clearance From Plasma (CLr) After Multiple Dose Administration (Day 5)

Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril)

Time frame: Day 5

Population: FAS

Arm	Measure	Group	Value (MEAN)	Dispersion
Mild Renal Impaired Subjects	Renal Clearance From Plasma (CLr) After Multiple Dose Administration (Day 5)	AHU377 day 5,multiple dose of LCZ696 400 mg Q.D	81.2 mL/hr	Standard Deviation 30.5
Mild Renal Impaired Subjects	Renal Clearance From Plasma (CLr) After Multiple Dose Administration (Day 5)	VAL489 day 5,multiple dose LCZ696 400 mg Q.D	141.6 mL/hr	Standard Deviation 84.7
Mild Renal Impaired Subjects	Renal Clearance From Plasma (CLr) After Multiple Dose Administration (Day 5)	LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D	253.1 mL/hr	Standard Deviation 99
Mild Renal Impaired Matched Healthy Subjects	Renal Clearance From Plasma (CLr) After Multiple Dose Administration (Day 5)	AHU377 day 5,multiple dose of LCZ696 400 mg Q.D	129.1 mL/hr	Standard Deviation 97
Mild Renal Impaired Matched Healthy Subjects	Renal Clearance From Plasma (CLr) After Multiple Dose Administration (Day 5)	VAL489 day 5,multiple dose LCZ696 400 mg Q.D	313.8 mL/hr	Standard Deviation 144.5
Mild Renal Impaired Matched Healthy Subjects	Renal Clearance From Plasma (CLr) After Multiple Dose Administration (Day 5)	LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D	499.0 mL/hr	Standard Deviation 251.3
Moderate Renal Impaired Subjects	Renal Clearance From Plasma (CLr) After Multiple Dose Administration (Day 5)	LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D	111.0 mL/hr	Standard Deviation 81.4
Moderate Renal Impaired Subjects	Renal Clearance From Plasma (CLr) After Multiple Dose Administration (Day 5)	AHU377 day 5,multiple dose of LCZ696 400 mg Q.D	48.9 mL/hr	Standard Deviation 36.3
Moderate Renal Impaired Subjects	Renal Clearance From Plasma (CLr) After Multiple Dose Administration (Day 5)	VAL489 day 5,multiple dose LCZ696 400 mg Q.D	73.2 mL/hr	Standard Deviation 43.1
Moderate Renal Impaired Matched Healthy Subjects	Renal Clearance From Plasma (CLr) After Multiple Dose Administration (Day 5)	AHU377 day 5,multiple dose of LCZ696 400 mg Q.D	143.9 mL/hr	Standard Deviation 145.2
Moderate Renal Impaired Matched Healthy Subjects	Renal Clearance From Plasma (CLr) After Multiple Dose Administration (Day 5)	VAL489 day 5,multiple dose LCZ696 400 mg Q.D	317.0 mL/hr	Standard Deviation 109
Moderate Renal Impaired Matched Healthy Subjects	Renal Clearance From Plasma (CLr) After Multiple Dose Administration (Day 5)	LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D	486.0 mL/hr	Standard Deviation 85.7

Primary

Systemic Clearance From Plasma Following Extravascular Administration (CL/F) After Multiple Dose Administration (Day 5)

Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril)

Time frame: Day 5

Arm	Measure	Group	Value (MEAN)	Dispersion
Mild Renal Impaired Subjects	Systemic Clearance From Plasma Following Extravascular Administration (CL/F) After Multiple Dose Administration (Day 5)	AHU377 day 5, multiple doses of LCZ696 400 mg Q.D	38261 mL/hr	Standard Deviation 14002
Mild Renal Impaired Subjects	Systemic Clearance From Plasma Following Extravascular Administration (CL/F) After Multiple Dose Administration (Day 5)	VAL489 day 5,multiple dose LCZ696 400 mg Q.D	4636 mL/hr	Standard Deviation 17080
Mild Renal Impaired Subjects	Systemic Clearance From Plasma Following Extravascular Administration (CL/F) After Multiple Dose Administration (Day 5)	LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D	NA mL/hr	—
Mild Renal Impaired Matched Healthy Subjects	Systemic Clearance From Plasma Following Extravascular Administration (CL/F) After Multiple Dose Administration (Day 5)	AHU377 day 5, multiple doses of LCZ696 400 mg Q.D	39137 mL/hr	Standard Deviation 10451
Mild Renal Impaired Matched Healthy Subjects	Systemic Clearance From Plasma Following Extravascular Administration (CL/F) After Multiple Dose Administration (Day 5)	VAL489 day 5,multiple dose LCZ696 400 mg Q.D	6499 mL/hr	Standard Deviation 3876
Mild Renal Impaired Matched Healthy Subjects	Systemic Clearance From Plasma Following Extravascular Administration (CL/F) After Multiple Dose Administration (Day 5)	LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D	NA mL/hr	—
Moderate Renal Impaired Subjects	Systemic Clearance From Plasma Following Extravascular Administration (CL/F) After Multiple Dose Administration (Day 5)	LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D	NA mL/hr	—
Moderate Renal Impaired Subjects	Systemic Clearance From Plasma Following Extravascular Administration (CL/F) After Multiple Dose Administration (Day 5)	AHU377 day 5, multiple doses of LCZ696 400 mg Q.D	42704 mL/hr	Standard Deviation 17238
Moderate Renal Impaired Subjects	Systemic Clearance From Plasma Following Extravascular Administration (CL/F) After Multiple Dose Administration (Day 5)	VAL489 day 5,multiple dose LCZ696 400 mg Q.D	4929 mL/hr	Standard Deviation 3260
Moderate Renal Impaired Matched Healthy Subjects	Systemic Clearance From Plasma Following Extravascular Administration (CL/F) After Multiple Dose Administration (Day 5)	AHU377 day 5, multiple doses of LCZ696 400 mg Q.D	37902 mL/hr	Standard Deviation 14487
Moderate Renal Impaired Matched Healthy Subjects	Systemic Clearance From Plasma Following Extravascular Administration (CL/F) After Multiple Dose Administration (Day 5)	VAL489 day 5,multiple dose LCZ696 400 mg Q.D	5988 mL/hr	Standard Deviation 6568
Moderate Renal Impaired Matched Healthy Subjects	Systemic Clearance From Plasma Following Extravascular Administration (CL/F) After Multiple Dose Administration (Day 5)	LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D	NA mL/hr	—

Primary

Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)

Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril)

Time frame: Day 1 and day 5

Arm	Measure	Group	Value (MEDIAN)
Mild Renal Impaired Subjects	Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	VAL489 day 1, single dose of LCZ696 400 mg	2.5 hr
Mild Renal Impaired Subjects	Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	LBQ657 day 1, single dose of LCZ696 400 mg	3 hr
Mild Renal Impaired Subjects	Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	AHU377 day 5, multiple doses of LCZ696 400 mg Q.D.	1 hr
Mild Renal Impaired Subjects	Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	VAL489 day 5,multiple doses LCZ696 400 mg Q.D.	2.5 hr
Mild Renal Impaired Subjects	Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	LBQ657 day 5, multiple doses of LCZ696 400 mg Q.D.	3 hr
Mild Renal Impaired Subjects	Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	AHU377 day 1, single dose of LCZ696 400 mg	1 hr
Mild Renal Impaired Matched Healthy Subjects	Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	VAL489 day 5,multiple doses LCZ696 400 mg Q.D.	2 hr
Mild Renal Impaired Matched Healthy Subjects	Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	VAL489 day 1, single dose of LCZ696 400 mg	2 hr
Mild Renal Impaired Matched Healthy Subjects	Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	AHU377 day 1, single dose of LCZ696 400 mg	0.5 hr
Mild Renal Impaired Matched Healthy Subjects	Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	AHU377 day 5, multiple doses of LCZ696 400 mg Q.D.	0.5 hr
Mild Renal Impaired Matched Healthy Subjects	Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	LBQ657 day 1, single dose of LCZ696 400 mg	2 hr
Mild Renal Impaired Matched Healthy Subjects	Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	LBQ657 day 5, multiple doses of LCZ696 400 mg Q.D.	3 hr
Moderate Renal Impaired Subjects	Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	AHU377 day 5, multiple doses of LCZ696 400 mg Q.D.	0.5 hr
Moderate Renal Impaired Subjects	Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	AHU377 day 1, single dose of LCZ696 400 mg	0.5 hr
Moderate Renal Impaired Subjects	Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	VAL489 day 5,multiple doses LCZ696 400 mg Q.D.	2 hr
Moderate Renal Impaired Subjects	Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	LBQ657 day 1, single dose of LCZ696 400 mg	3 hr
Moderate Renal Impaired Subjects	Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	VAL489 day 1, single dose of LCZ696 400 mg	2 hr
Moderate Renal Impaired Subjects	Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	LBQ657 day 5, multiple doses of LCZ696 400 mg Q.D.	3 hr
Moderate Renal Impaired Matched Healthy Subjects	Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	VAL489 day 1, single dose of LCZ696 400 mg	2 hr
Moderate Renal Impaired Matched Healthy Subjects	Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	AHU377 day 5, multiple doses of LCZ696 400 mg Q.D.	0.5 hr
Moderate Renal Impaired Matched Healthy Subjects	Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	LBQ657 day 5, multiple doses of LCZ696 400 mg Q.D.	3 hr
Moderate Renal Impaired Matched Healthy Subjects	Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	AHU377 day 1, single dose of LCZ696 400 mg	0.5 hr
Moderate Renal Impaired Matched Healthy Subjects	Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	LBQ657 day 1, single dose of LCZ696 400 mg	3 hr
Moderate Renal Impaired Matched Healthy Subjects	Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	VAL489 day 5,multiple doses LCZ696 400 mg Q.D.	2 hr

Secondary

Change in Mean 24-hours Sodium Clearance From Baseline to Day 7

Sodium clearance will be measured in urine from baseline until Day 7

Time frame: From baseline to Day 7

Population: FAS

Arm	Measure	Group	Value (MEAN)	Dispersion
Mild Renal Impaired Subjects	Change in Mean 24-hours Sodium Clearance From Baseline to Day 7	Baseline	107.13 mmol/day	Standard Deviation 51.709
Mild Renal Impaired Subjects	Change in Mean 24-hours Sodium Clearance From Baseline to Day 7	Day 1	143.24 mmol/day	Standard Deviation 36.293
Mild Renal Impaired Subjects	Change in Mean 24-hours Sodium Clearance From Baseline to Day 7	Day 2	118.4 mmol/day	Standard Deviation 48.036
Mild Renal Impaired Subjects	Change in Mean 24-hours Sodium Clearance From Baseline to Day 7	Day 3	117.38 mmol/day	Standard Deviation 51.798
Mild Renal Impaired Subjects	Change in Mean 24-hours Sodium Clearance From Baseline to Day 7	Day 4	140.70 mmol/day	Standard Deviation 52.127
Mild Renal Impaired Subjects	Change in Mean 24-hours Sodium Clearance From Baseline to Day 7	Day 5	161.68 mmol/day	Standard Deviation 80.545
Mild Renal Impaired Subjects	Change in Mean 24-hours Sodium Clearance From Baseline to Day 7	Day 6	163.32 mmol/day	Standard Deviation 13.81
Mild Renal Impaired Subjects	Change in Mean 24-hours Sodium Clearance From Baseline to Day 7	Day 7	141.63 mmol/day	Standard Deviation 72.63
Mild Renal Impaired Matched Healthy Subjects	Change in Mean 24-hours Sodium Clearance From Baseline to Day 7	Day 5	133.50 mmol/day	Standard Deviation 53.596
Mild Renal Impaired Matched Healthy Subjects	Change in Mean 24-hours Sodium Clearance From Baseline to Day 7	Day 4	133.38 mmol/day	Standard Deviation 60.656
Mild Renal Impaired Matched Healthy Subjects	Change in Mean 24-hours Sodium Clearance From Baseline to Day 7	Day 1	185.75 mmol/day	Standard Deviation 38.592
Mild Renal Impaired Matched Healthy Subjects	Change in Mean 24-hours Sodium Clearance From Baseline to Day 7	Day 7	117.50 mmol/day	Standard Deviation 48.794
Mild Renal Impaired Matched Healthy Subjects	Change in Mean 24-hours Sodium Clearance From Baseline to Day 7	Day 6	129.38 mmol/day	Standard Deviation 65.6
Mild Renal Impaired Matched Healthy Subjects	Change in Mean 24-hours Sodium Clearance From Baseline to Day 7	Day 3	127.50 mmol/day	Standard Deviation 56.488
Mild Renal Impaired Matched Healthy Subjects	Change in Mean 24-hours Sodium Clearance From Baseline to Day 7	Day 2	134.88 mmol/day	Standard Deviation 46.603
Mild Renal Impaired Matched Healthy Subjects	Change in Mean 24-hours Sodium Clearance From Baseline to Day 7	Baseline	150.25 mmol/day	Standard Deviation 50.349
Moderate Renal Impaired Subjects	Change in Mean 24-hours Sodium Clearance From Baseline to Day 7	Day 6	106.42 mmol/day	Standard Deviation 25.427
Moderate Renal Impaired Subjects	Change in Mean 24-hours Sodium Clearance From Baseline to Day 7	Day 2	95.63 mmol/day	Standard Deviation 37.799
Moderate Renal Impaired Subjects	Change in Mean 24-hours Sodium Clearance From Baseline to Day 7	Day 3	97.89 mmol/day	Standard Deviation 29.745
Moderate Renal Impaired Subjects	Change in Mean 24-hours Sodium Clearance From Baseline to Day 7	Day 4	107.38 mmol/day	Standard Deviation 43.007
Moderate Renal Impaired Subjects	Change in Mean 24-hours Sodium Clearance From Baseline to Day 7	Day 5	104.45 mmol/day	Standard Deviation 34.775
Moderate Renal Impaired Subjects	Change in Mean 24-hours Sodium Clearance From Baseline to Day 7	Day 7	102.02 mmol/day	Standard Deviation 45.256
Moderate Renal Impaired Subjects	Change in Mean 24-hours Sodium Clearance From Baseline to Day 7	Baseline	110.65 mmol/day	Standard Deviation 40.169
Moderate Renal Impaired Subjects	Change in Mean 24-hours Sodium Clearance From Baseline to Day 7	Day 1	129.26 mmol/day	Standard Deviation 36.51
Moderate Renal Impaired Matched Healthy Subjects	Change in Mean 24-hours Sodium Clearance From Baseline to Day 7	Day 2	134.38 mmol/day	Standard Deviation 38.774
Moderate Renal Impaired Matched Healthy Subjects	Change in Mean 24-hours Sodium Clearance From Baseline to Day 7	Day 3	141.00 mmol/day	Standard Deviation 43.808
Moderate Renal Impaired Matched Healthy Subjects	Change in Mean 24-hours Sodium Clearance From Baseline to Day 7	Day 1	196.13 mmol/day	Standard Deviation 51.99
Moderate Renal Impaired Matched Healthy Subjects	Change in Mean 24-hours Sodium Clearance From Baseline to Day 7	Baseline	158.38 mmol/day	Standard Deviation 56.835
Moderate Renal Impaired Matched Healthy Subjects	Change in Mean 24-hours Sodium Clearance From Baseline to Day 7	Day 4	142.88 mmol/day	Standard Deviation 40.47
Moderate Renal Impaired Matched Healthy Subjects	Change in Mean 24-hours Sodium Clearance From Baseline to Day 7	Day 7	146.25 mmol/day	Standard Deviation 69.405
Moderate Renal Impaired Matched Healthy Subjects	Change in Mean 24-hours Sodium Clearance From Baseline to Day 7	Day 6	184.25 mmol/day	Standard Deviation 81.31
Moderate Renal Impaired Matched Healthy Subjects	Change in Mean 24-hours Sodium Clearance From Baseline to Day 7	Day 5	178.00 mmol/day	Standard Deviation 44.156

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

Pharmacokinetics of LCZ696 in Subjects With Mild and Moderate Renal Impairment Compared to Healthy Subjects With Normal Renal Function

Conditions

Keywords

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Participants by arm

Baseline characteristics

Adverse events

Outcome results

Accumulation Ratio (Racc) After Multiple Dose Administration (Day 5)

Amount of Drug Excreted Into the Urine From Time Zero to 24-hours Post-dose (Ae0-24) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)

Area Under the Concentration-time Curve (AUC0-24) From Time Zero to 24- Hour Post-dose (Day 1), and After Multiple Dose Administration (Day 5)

Elimination Half-life (t1/2) After Multiple Dose (Day 5) Administration

Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)

Renal Clearance From Plasma (CLr) After Multiple Dose Administration (Day 5)

Systemic Clearance From Plasma Following Extravascular Administration (CL/F) After Multiple Dose Administration (Day 5)

Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)

Change in Mean 24-hours Sodium Clearance From Baseline to Day 7