A study to assess the pharmacokinetics of LCZ696 in subjects with hepatic impairment compared to matched healthy subjects

• Register: EUCTR
• Last refreshed on: 4 November 2013
• Main ID: EUCTR2012-000983-27-DE
• Date of registration: 14/08/2012
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A study to assess the pharmacokinetics of LCZ696 in subjects with hepatic impairment compared to matched healthy subjects
• Scientific 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
• Date of first enrolment: 07/09/2012
• Target sample size: 32
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-000983-27
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: no Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: yes Other trial design description: single-dose If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Healthy volunteers Number of treatment arms in the trial: 3

Countries of recruitment

Germany

Contacts

• Name: Medical Competence Center
• Affiliation: Novartis Pharma GmbH

• Name: Medical Competence Center
• Affiliation: Novartis Pharma GmbH

Key inclusion & exclusion 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 16
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 16

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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Mild and moderate hepatic impairment
MedDRA version: 14.1 Level: PT Classification code 10024670 Term: Liver disorder System Organ Class: 10019805 - Hepatobiliary disorders

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Product Code: LCZ696
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: not assigned yet
CAS Number: 936623-90-4
Current Sponsor code: LCZ696
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

Main Objective: 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.

Primary end point(s): - 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).
- Area under the plasma concentration-time profile from time zero extrapolated to infinite time [AUC(0-inf)] of LCZ696 analytes (AHU377, LBQ657, and valsartan).
- Maximum plasma concentration (Cmax) for LCZ696 analytes (AHU377, LBQ657, and valsartan).

Secondary Objective: To assess safety and tolerability of LCZ696 200 mg administered as single dose in subjects with mild and moderate hepatic impairment and their matched healthy control subjects.

Timepoint(s) of evaluation of this end point: From pre-dose on Day 1 until 96h post-dose (Day 5).

Secondary Outcome(s)

Secondary end point(s): Number of participants with adverse events, serious adverse events and death.

Timepoint(s) of evaluation of this end point: From the screening visit until Day 5.

Secondary ID(s)

CLCZ696B2203

Source(s) of Monetary Support

Novartis Pharma Services AG