Clinical trial NCT01621633: A Study of LCZ696 in Subjects With Mild and Moderate Hepatic Impairment Compared With Normal Healthy Volunteers
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatic Impairment
Keywords: hepatic impairment
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-06-18
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL

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


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/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.

Primary outcomes:
measure: 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)
timeFrame: From pre-dose on Day 1 until 96h post-dose (Day 5)
measure: Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time [AUCinf)] of LCZ696 Analytes (AHU377, LBQ657, and Valsartan)
timeFrame: From pre-dose on Day 1 until 96h post-dose (Day 5)
measure: Maximum Plasma Concentration (Cmax) for LCZ696 Analytes (AHU377, LBQ657, and Valsartan)
timeFrame: From pre-dose on Day 1 until 96h post-dose (Day 5)
Secondary outcomes:
measure: Number of Participants With Adverse Events, Serious Adverse Events and Death
timeFrame: From the screening visit until Day 5
Other outcomes:
Locations:
city: Grunstadt
country: Germany
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: