A Study of LCZ696 in Subjects With Mild and Moderate Hepatic Impairment Compared With Normal Healthy Volunteers

Phase 2

Completed

Brief Summary: This is a study to characterize the pharmacokinetics as well as safety and tolerability of a single oral dose of LCZ696 200 mg in subjects with mild and moderate hepatic impairment compared to matched healthy subjects

Recruitment & Eligibility

Inclusion Criteria

All subjects:
- Male and female subjects aged 18-75 years.
- Body weight at least 55 kg with a body mass index between 18-35 kg/m2.
Hepatic impairment subjects:
- Mild or moderate hepatic impairment.

Exclusion Criteria

All subjects:
- Clinical manifestations of postural symptomatic hypotension at screening or baseline.
- History of hypersensitivity to LCZ696 or to drugs of similar classes.
Hepatic impairment subjects:
- Hepatic impairment due to non-liver disease.
- Treatment with any vasodilator, autonomic alpha blocker or beta2 agonist within 2 weeks of dosing.
- Encephalopathyy Stage III or IV.
- Primary biliary liver cirrhosis or biliary obstruction.
- History of gastro-intestinal bleeding within 3 months prior to screening.
Healthy subjects:
- Any surgical or medical condition which might significantly alter the distribution, or excretion of drugs, or which may jeopardize the subject in case of participation in the study.
- Use of prescription drugs, herbal supplements, and/or over-the-counter medication, dietary supplements (vitamins included) within 2 weeks prior to initial dosing.

Other protocol-defined inclusion/exclusion criteria may apply.

Arm && Interventions

Group	Intervention	Description
Group 1: mild hepatic impairment	LCZ696	LCZ696 200 mg, given as a single oral dose
Group 2: moderate hepatic impairment	LCZ696	LCZ696 200 mg, given as a single oral dose
Group 3: healthy volunteers	LCZ696	LCZ696 200 mg, given as a single oral dose. Each healthy volunteer will match in race, age (±5 years), gender, weight (±15%) to an individual subject with hepatic impairment in groups 1 and 2

Primary Outcome Measures

Name	Time	Method
Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of LCZ696 Analytes (AHU377, LBQ657, and Valsartan)	From pre-dose on Day 1 until 96h post-dose (Day 5)	Blood samples were taken on Day 1 (treatment day) within 60 minutes prior to dosing, then, 0.5,1,1.5,2,3,4,6,8,12 hours after the dosing and on Days 2, 3, 4 and 5 post dosing
Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time [AUCinf)] of LCZ696 Analytes (AHU377, LBQ657, and Valsartan)	From pre-dose on Day 1 until 96h post-dose (Day 5)	Blood samples were taken on Day 1 (treatment day) within 60 minutes prior to dosing, then, 0.5,1,1.5,2,3,4,6,8,12 hours after the dosing and on Days 2, 3, 4 and 5 post dosing
Maximum Plasma Concentration (Cmax) for LCZ696 Analytes (AHU377, LBQ657, and Valsartan)	From pre-dose on Day 1 until 96h post-dose (Day 5)	Blood samples were taken on Day 1 (treatment day) within 60 minutes prior to dosing, then, 0.5,1,1.5,2,3,4,6,8,12 hours after the dosing and on Days 2, 3, 4 and 5 post dosing

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events, Serious Adverse Events and Death	From the screening visit until Day 5	Adverse events, serious adverse events and death were monitored from screening to end of study