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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01621633
First received: June 14, 2012
Last updated: January 16, 2013
Last verified: January 2013
  Purpose

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


Condition Intervention Phase
Hepatic Impairment
Drug: LCZ696
Phase 2

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

Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    Blood samples will be 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 [AUC(0-inf)] of LCZ696 analytes (AHU377, LBQ657, and valsartan) [ Time Frame: From pre-dose on Day 1 until 96h post-dose (Day 5) ] [ Designated as safety issue: No ]
    Blood samples will be 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) ] [ Designated as safety issue: No ]
    Blood samples will be 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:
  • Number of participants with adverse events, serious adverse events and death [ Time Frame: From the screening visit until Day 5 ] [ Designated as safety issue: No ]
    Monitoring of adverse events, serious adverse events and death from screening to end of study


Enrollment: 32
Study Start Date: September 2012
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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/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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01621633

Locations
Germany
Novartis Investigative Site
Grunstadt, Germany, D-67269
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01621633     History of Changes
Other Study ID Numbers: CLCZ696B2203, 2012-000983-27
Study First Received: June 14, 2012
Last Updated: January 16, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Novartis:
hepatic impairment

Additional relevant MeSH terms:
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on July 20, 2014