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

Hepatic Impairment Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01621633
• Other study ID #: CLCZ696B2203
• Secondary ID: 2012-000983-27
• Status: Completed
• Phase: Phase 2
• First received: June 14, 2012
• Last updated: July 11, 2015
• Start date: September 2012
• Est. completion date: January 2013

Study information

• Verified date: July 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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 information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: January 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 75 Years

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Hepatic Impairment
• Liver Diseases

Intervention

Drug:
• LCZ696

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Grunstadt

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Primary	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)	No
Primary	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)	No
Secondary	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	Yes