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

• ClinicalTrials.gov Identifier: NCT01621633
• Recruitment Status: Completed
• First Posted: June 18, 2012
• Results First Posted: August 10, 2015
• Last Update Posted: August 10, 2015
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

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

Condition or disease	Intervention/treatment	Phase
Hepatic Impairment	Drug: LCZ696	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 32 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (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
• Study Start Date: September 2012
• Actual Primary Completion Date: January 2013
• Actual Study Completion Date: January 2013

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. 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) ]
   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
2. Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time [AUCinf)] of LCZ696 Analytes (AHU377, LBQ657, and Valsartan) [ Time Frame: From pre-dose on Day 1 until 96h post-dose (Day 5) ]
   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
3. 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) ]
   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

Secondary Outcome Measures :

1. Number of Participants With Adverse Events, Serious Adverse Events and Death [ Time Frame: From the screening visit until Day 5 ]
   Adverse events, serious adverse events and death were monitored from screening to end of study

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Locations

Germany

Novartis Investigative Site

Grunstadt, Germany, D-67269

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01621633
• Other Study ID Numbers: CLCZ696B2203; 2012-000983-27 ( EudraCT Number )
• First Posted: June 18, 2012
• Results First Posted: August 10, 2015
• Last Update Posted: August 10, 2015
• Last Verified: July 2015

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

hepatic impairment

Additional relevant MeSH terms:

Liver Diseases; Digestive System Diseases; Sacubitril and valsartan sodium hydrate drug combination; Angiotensin Receptor Antagonists; Molecular Mechanisms of Pharmacological Action