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

Study Overview
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Brief Summary
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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

Official Title
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A Single-dose, Open-label Parallel-group Study to Assess the Pharmacokinetics of LCZ696 in Subjects With Hepatic Impairment Compared to Matched Healthy Subjects

Conditions
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Hepatic Impairment

Intervention / Treatment
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* Drug: LCZ696


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: mild hepatic impairment<br>LCZ696 200 mg, given as a single oral dose | Drug: LCZ696<br> <br> |
| Experimental: Group 2: moderate hepatic impairment<br>LCZ696 200 mg, given as a single oral dose | Drug: LCZ696<br> <br> |
| Experimental: Group 3: healthy volunteers<br>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 | Drug: LCZ696<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 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 | From pre-dose on Day 1 until 96h post-dose (Day 5) | 
| Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time [AUCinf)] of LCZ696 Analytes (AHU377, LBQ657, and Valsartan) | 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 | From pre-dose on Day 1 until 96h post-dose (Day 5) | 
| Maximum Plasma Concentration (Cmax) for LCZ696 Analytes (AHU377, LBQ657, and Valsartan) | 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 | From pre-dose on Day 1 until 96h post-dose (Day 5) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events, Serious Adverse Events and Death | Adverse events, serious adverse events and death were monitored from screening to end of study | From the screening visit until Day 5 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hepatic impairment