Mild and Moderate Renal Impairment Clinical Trial
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
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.
| Status | Completed |
| Enrollment | 32 |
| Est. completion date | August 2014 |
| Est. primary completion date | August 2014 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | Both |
| Age group | 18 Years to 65 Years |
| Eligibility |
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 |
Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science
| Country | Name | City | State |
|---|---|---|---|
| Germany | Novartis Investigative Site | Neuss | |
| Russian Federation | Novartis Investigative Site | Moscow | |
| Serbia | Novartis Investigative Site | Belgrade |
| Lead Sponsor | Collaborator |
|---|---|
| Novartis Pharmaceuticals |
Germany, Russian Federation, Serbia,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5) | Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril) | Day 1 and day 5 | No |
| Primary | Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5) | Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril) | Day 1, day 5 | No |
| Primary | 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) | Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril) | Day 1 and day 5 | No |
| Primary | Elimination Half-life (t1/2) After Multiple Dose (Day 5) Administration | Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril) | Day 5 | No |
| Primary | Systemic Clearance From Plasma Following Extravascular Administration (CL/F) After Multiple Dose Administration (Day 5) | Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril) | Day 5 | No |
| Primary | Accumulation Ratio (Racc) After Multiple Dose Administration (Day 5) | Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril) | Day 5 | No |
| Primary | Renal Clearance From Plasma (CLr) After Multiple Dose Administration (Day 5) | Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril) | Day 5 | No |
| Primary | 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) | Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril) | Day 1 and Day 5 | No |
| Secondary | Change in Mean 24-hours Sodium Clearance From Baseline to Day 7 | Sodium clearance will be measured in urine from baseline until Day 7 | From baseline to Day 7 | No |