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

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

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

Study Overview

• Status: Completed
• Conditions: Hepatic Impairment
• Intervention / Treatment: Drug: LCZ696

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Grunstadt, Germany, D-67269
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: mild hepatic impairment; LCZ696 200 mg, given as a single oral dose	Drug: LCZ696
Experimental: Group 2: moderate hepatic impairment; LCZ696 200 mg, given as a single oral dose	Drug: LCZ696
Experimental: 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	Drug: LCZ696

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: June 14, 2012
• First Submitted That Met QC Criteria: June 14, 2012
• First Posted (Estimate): June 18, 2012

Study Record Updates

• Last Update Posted (Estimate): August 10, 2015
• Last Update Submitted That Met QC Criteria: July 11, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: hepatic impairment
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Molecular Mechanisms of Pharmacological Action; Angiotensin Receptor Antagonists; Sacubitril and valsartan sodium hydrate drug combination
• Other Study ID Numbers: CLCZ696B2203; 2012-000983-27 (EudraCT Number)