- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01569815
Pharmacokinetics of LCZ696 in Subjects With Mild and Moderate Renal Impairment Compared to Healthy Subjects With Normal Renal Function
September 25, 2015 updated by: Novartis Pharmaceuticals
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
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
32
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Neuss, Germany, 41460
- Novartis Investigative Site
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Moscow, Russian Federation, 117292
- Novartis Investigative Site
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Belgrade, Serbia
- Novartis Investigative Site
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Male, and female subjects of non-child bearing potential,
- Subjects were to weigh at least 50 kg to participate in the study,
- and body mass index < 40 kg/m2
- Subjects were able to communicate well with the investigator, to understand and comply with the requirements of the study;
- Subjects were able to understand and sign the written informed consent;
For renal insufficient subjects:
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
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
- A serum creatinine with a calculated CrCl of >80 mL/min
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:
- Current use of ACE inhibitors, valsartan, and drugs that were known as CYP2C9 substrates, potassium-sparing diuretics;
- Smokers;
- History of renal transplant at any time in the past and on immunosuppressant therapy;
- Dialysis patients;
- Medical history of clinically significant ECG abnormalities or a family history of a prolonged QT-interval syndrome;
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: BASIC_SCIENCE
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: LCZ696 400 mg
LCZ696 400 mg once daily for 5 days
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LCZ696 400 mg once daily
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)
Time Frame: Day 1 and day 5
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Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril)
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Day 1 and day 5
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Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)
Time Frame: Day 1, day 5
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Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril)
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Day 1, day 5
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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 and day 5
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Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril)
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Day 1 and day 5
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Elimination Half-life (t1/2) After Multiple Dose (Day 5) Administration
Time Frame: Day 5
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Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril)
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Day 5
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Systemic Clearance From Plasma Following Extravascular Administration (CL/F) After Multiple Dose Administration (Day 5)
Time Frame: Day 5
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Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril)
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Day 5
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Accumulation Ratio (Racc) After Multiple Dose Administration (Day 5)
Time Frame: Day 5
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Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril)
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Day 5
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Renal Clearance From Plasma (CLr) After Multiple Dose Administration (Day 5)
Time Frame: Day 5
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Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril)
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Day 5
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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 and Day 5
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Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril)
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Day 1 and Day 5
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Mean 24-hours Sodium Clearance From Baseline to Day 7
Time Frame: From baseline to Day 7
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Sodium clearance will be measured in urine from baseline until Day 7
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From baseline to Day 7
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
February 1, 2009
Primary Completion (ACTUAL)
August 1, 2014
Study Completion (ACTUAL)
August 1, 2014
Study Registration Dates
First Submitted
March 30, 2012
First Submitted That Met QC Criteria
March 30, 2012
First Posted (ESTIMATE)
April 3, 2012
Study Record Updates
Last Update Posted (ESTIMATE)
October 19, 2015
Last Update Submitted That Met QC Criteria
September 25, 2015
Last Verified
September 1, 2015
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CLCZ696A2204
- 2007-005480-96 (EUDRACT_NUMBER)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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