Pharmacokinetics of LCZ696 in Subjects With Mild and Moderate Renal Impairment Compared to Healthy Subjects With Normal Renal Function

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01569815
First received: March 30, 2012
Last updated: April 8, 2012
Last verified: April 2012
  Purpose

The purpose of this study is to determine the multiple dose pharmacokinetics of LCZ696 and its metabolites in subjects with mild to moderate renal impairment and to evaluate the safety of LCZ696 in this population.


Condition Intervention Phase
Mild and Moderate Renal Impairment
Drug: LCZ696
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: An Open Label, Parallel-group Study to Determine Multiple Dose Pharmacokinetics of LCZ696 and Its Metabolites in Subjects With Mild and Moderate Renal Impairment Compared to Matched Healthy Subjects With Normal Renal Function

Further study details as provided by Novartis:

Primary Outcome Measures:
  • Time to reach maximum peak plasma concentration (Tmax) after single dose (Day 1), and after multiple dose administration (Day 5) [ Time Frame: Day 1 to 2 (at pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 h post-dose), day 5 to 8 (at pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 h post-dose) ] [ Designated as safety issue: No ]
    Blood samples will be collected for the determination of plasma concentrations of valsartan, AHU377 and LBQ657

  • Maximum peak plasma concentration (Cmax) observed after single dose (Day 1), and after multiple dose administration (Day 5) [ Time Frame: Day 1 to 2 (at pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 h post-dose), day 5 to 8 (at pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 h post-dose) ] [ Designated as safety issue: No ]
    Blood samples will be collected for the determination of plasma concentrations of valsartan, AHU377 and LBQ657

  • Area under the concentration-time curve (AUC0-24) from time zero to 24- hour post-dose (Day 1), and after multiple dose administration (Day 5) [ Time Frame: Day 1 to 2 (at pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 h post-dose), day 5 to 8 (at pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 h post-dose) ] [ Designated as safety issue: No ]
    Blood samples will be collected for the determination of plasma concentrations of valsartan, AHU377 and LBQ657

  • Elimination half-life (t1/2) after multiple dose (Day 5) administration [ Time Frame: Day 5 to 8 (at pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 h post-dose) ] [ Designated as safety issue: No ]
    Blood samples will be collected for the determination of plasma concentrations of valsartan, AHU377 and LBQ657

  • Systemic clearance from plasma following extravascular administration (CL/F) after multiple dose administration (Day 5) [ Time Frame: Day 5 to 8 (at pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 h post-dose) ] [ Designated as safety issue: No ]
    Blood samples will be collected for the determination of plasma concentrations of valsartan, AHU377 and LBQ657

  • Accumulation ratio (Racc) after multiple dose administration (Day 5) [ Time Frame: Day 5 to 8 (at pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 h post-dose) ] [ Designated as safety issue: No ]
    Blood samples will be collected for the determination of plasma concentrations of valsartan, AHU377 and LBQ657

  • Renal clearance from plasma (CLr) after multiple dose administration (Day 5) [ Time Frame: Day 5 to 8 (at pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 h post-dose) ] [ Designated as safety issue: No ]
    Blood samples will be collected for the determination of plasma concentrations of valsartan, AHU377 and LBQ657

  • Amount of drug excreted into the urine from time zero to 24-hours post-dose (Ae0-24) after single dose (Day 1), and after multiple dose administration (Day 5) [ Time Frame: Day 1, 5, 6, 7: pre-dose, 0-6, 6-12 and 12-24 hour ] [ Designated as safety issue: No ]
    Blood samples will be collected for the determination of plasma concentrations of valsartan, AHU377 and LBQ657


Secondary Outcome Measures:
  • Number of patients with adverse events, serious adverse events and death [ Time Frame: Screening to Day 8 ] [ Designated as safety issue: Yes ]
    Adverse events will be based on evaluation of physical signs, electrocardiograms and clinical laboratory assessments

  • Change in mean 24-hours sodium clearance from baseline to Day 8 [ Time Frame: From baseline to Day 8 (Day 1, 5, 6, 7: pre-dose, 0-6, 6-12 and 12-24 hour ) ] [ Designated as safety issue: No ]
    Sodium clearance will be measured in urine from baseline until Day 8


Enrollment: 32
Study Start Date: February 2009
Study Completion Date: August 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LCZ696 400 mg
LCZ696 400 mg once daily for 5 days
Drug: LCZ696
LCZ696 400 mg once daily

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Male, and female subjects of non-child bearing potential,
  2. Subjects were to weigh at least 50 kg to participate in the study,
  3. and body mass index < 40 kg/m2
  4. Subjects were able to communicate well with the investigator, to understand and comply with the requirements of the study;
  5. Subjects were able to understand and sign the written informed consent;

For renal insufficient subjects:

  1. stable renal disease without evidence of renal progressive

    • mild renal function: calculated CrCl of 50-≤80 mL/min
    • moderate renal function: calculated CrCl of 30-<50 mL/min
  2. Vital signs:

    • oral body temperature between 35.0-37.8 °C
    • systolic blood pressure, 95-180 mm Hg
    • diastolic blood pressure, 60-110 mm Hg
    • pulse rate, 54-95 bpm

For healthy subjects only

  1. A serum creatinine with a calculated CrCl of >80 mL/min
  2. Vital signs:

    • oral body temperature between 35.0-37.2 °C
    • systolic blood pressure, 95-140 mm Hg
    • diastolic blood pressure, 60-100 mm Hg
    • pulse rate, 45-90 bpm

Exclusion Criteria:

  1. Current use of ACE inhibitors, valsartan, and drugs that were known as CYP2C9 substrates, potassium-sparing diuretics;
  2. Smokers;
  3. History of renal transplant at any time in the past and on immunosuppressant therapy;
  4. Dialysis patients;
  5. Medical history of clinically significant ECG abnormalities or a family history of a prolonged QT-interval syndrome;
  6. Any surgical or medical condition which may significantly alter the absorption, distribution, metabolism or excretion of any drug substance; Other protocol defined inclusion/exclusion criteria may apply
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01569815

Locations
Germany
Novartis Investigative Site
Neuss, Germany
Russian Federation
Novartis Investigative Site
Moscow, Russian Federation
Serbia
Novartis Investigative site
Belgrade, Serbia
Sponsors and Collaborators
Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01569815     History of Changes
Other Study ID Numbers: CLCZ696A2204, 2007-005480-96
Study First Received: March 30, 2012
Last Updated: April 8, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Russia: Ministry of Health of the Russian Federation
Serbia and Montenegro: Agency for Drugs and Medicinal Devices

Keywords provided by Novartis:
Renal Impairment,
LCZ696

Additional relevant MeSH terms:
Renal Insufficiency
Kidney Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on April 17, 2014