A Single-dose, Open-label Parallel-group Study to Assess the Pharmacokinetics of LCZ696 in Subjects With Hepatic Impairment Compared to Matched Healthy Subjects
Overview
- Phase
- Phase 2
- Intervention
- LCZ696
- Conditions
- Hepatic Impairment
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 32
- Locations
- 1
- Primary Endpoint
- 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)
- Status
- Completed
- Last Updated
- 10 years ago
Overview
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
Investigators
Eligibility Criteria
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/m
- •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:
Arms & Interventions
Group 1: mild hepatic impairment
LCZ696 200 mg, given as a single oral dose
Intervention: LCZ696
Group 2: moderate hepatic impairment
LCZ696 200 mg, given as a single oral dose
Intervention: LCZ696
Group 3: healthy volunteers
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
Intervention: LCZ696
Outcomes
Primary Outcomes
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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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 Outcomes
- Number of Participants With Adverse Events, Serious Adverse Events and Death(From the screening visit until Day 5)