Multiple Dose Pharmacokinetics of LCZ696 and Its Metabolites in Subjects With Severe Renal Impairment vs. Matched 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 Severe Renal Impairment Compared to Matched Healthy Subjects With Normal Renal Function

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01569828

Enrollment

Registered

2012-04-03

Start date

2009-03-31

Completion date

2009-09-30

Last updated

2015-09-29

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

Conditions

Healthy Volunteer, Pharmacokinetics, Renal Impaired

Keywords

LCZ696, pharmacokinetics

Brief summary

An open label, parallel-group study to determine multiple dose pharmacokinetics of LCZ696 and its metabolites in subjects with severe renal impairment compared to matched healthy subjects with normal renal function

Interventions

DRUGLCZ696A

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Yes

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Measure	Time frame	Description
AUC 0-24h After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	1 and 5 days	—
Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	1 and 5 days	—
(Cmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)	1 and 5 days	—
CLr After Multiple Dose Administration (Day 5)	5 days	Summary statistics for plasma PK parameters following 5 days QD dose of 400mg LCZ696
T1/2 After Multiple Dose Administration (Day 5)	5 days	Summary statistics for plasma PK parameters following 5 days QD dose of 400mg LCZ696
CL/F After Multiple Dose Administration (Day 5)	5 days	Summary statistics for plasma PK parameters following 5 days QD dose of 400mg LCZ696

Secondary

Measure	Time frame
24 hr Sodium Urinary Excretion in Subjects With Severe Renal Impairment and Their Matched Healthy Volunteers	5 days

Countries

Germany, Russia, Serbia

Participant flow

Participants by arm

Arm	Count
Severe Renal Impaired Subjects Subjects with severe (CrCl from \<30 mL/min), renal function who were otherwise in good health as determined by past medical history, physical examination, electrocardiogram, vital signs (measured after 3 minutes rest in the supine position) which are within the following ranges; 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), laboratory tests and urinalysis. Creatinine clearance (CrCl) was calculated by the Cockcroft-Gault (CG) formula with patient stratification based on the screening serum creatinine measurement. Once daily administration of 400 mg LCZ696 p.o. for 5 days	6
Matched Healthy Volunteers All healthy volunteers were matched by age (±5 years), sex and BMI (±10%) to the renal subjects enrolled into the study. Subjects were to be in good health as determined by past medical history, physical examination, electrocardiogram, vital signs (measured after 3 minutes rest in the supine position) which are within the following ranges; 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), laboratory tests and urinalysis. Healthy subjects must have a CrCl of \>80 mL/min. Once daily administration of 400 mg LCZ696 p.o. for 5 days	6
Total	12

Baseline characteristics

Characteristic	Severe Renal Impaired Subjects	Matched Healthy Volunteers	Total
Age, Continuous	53.8 years STANDARD_DEVIATION 7.76	52.5 years STANDARD_DEVIATION 6.98	53.2 years STANDARD_DEVIATION 7.07
Sex: Female, Male Female	3 Participants	3 Participants	6 Participants
Sex: Female, Male Male	3 Participants	3 Participants	6 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	6 / 6	5 / 6
serious Total, serious adverse events	0 / 6	0 / 6