Sodium Excretion of LCZ696 in Patients With Hypertension; Heart Failure and Healthy Volunteers
- Registration Number
- NCT01353508
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
Assess mechanism of action of LCZ696 related to sodium excretion.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 32
- Patients with heart failure: documented NYHA class II-III heart failure
- Patients with hypertension: stable hypertensive medication for the preceding 2 months
- Women of childbearing potential
- History of recent myocardial infarction
- History of dialysis or renal transplant
- Patients with type 1 diabetes mellitus
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description LCZ696 to Valsartan - Heart Failure (HF) cohort LCZ696 Participants in this arm received Valsartan 160 mg twice daily (bid) during open-label run-in, LCZ696 200 mg bid double blind treatment during period 1, Valsartan 160 mg bid during wash-out, and Valsartan 160 mg bid double blind treatment during period 2. Valsartan to LCZ696 - HF Cohort LCZ696 Participants in this arm received Valsartan 160 mg twice daily bid during open-label run-in, Valsartan 160 mg bid during period 1, Valsartan 160 mg bid during wash-out, and LCZ696 200 mg bid double blind treatment during period 2. Valsartan to LCZ696 - HTN cohort Valsartan Participants in this arm received Valsartan 320 mg qd during open-label run-in, Valsartan 320 mg qd during period 1, Valsartan 320 mg qd during wash-out, and LCZ696 400 qd bid double blind treatment during period 2. Valsartan to LCZ696 - HTN cohort LCZ696 Participants in this arm received Valsartan 320 mg qd during open-label run-in, Valsartan 320 mg qd during period 1, Valsartan 320 mg qd during wash-out, and LCZ696 400 qd bid double blind treatment during period 2. LCZ696 to Valsartan - Hypertension (HTN) cohort LCZ696 Participants in this arm received Valsartan 320 mg once daily (qd) during open-label run-in, LCZ696 400 mg qd double blind treatment during period 1, Valsartan 320 mg qd during wash-out, and Valsartan 320 mg qd double blind treatment during period 2. LCZ696 to Valsartan - Heart Failure (HF) cohort Valsartan Participants in this arm received Valsartan 160 mg twice daily (bid) during open-label run-in, LCZ696 200 mg bid double blind treatment during period 1, Valsartan 160 mg bid during wash-out, and Valsartan 160 mg bid double blind treatment during period 2. LCZ696 to Valsartan - Hypertension (HTN) cohort Valsartan Participants in this arm received Valsartan 320 mg once daily (qd) during open-label run-in, LCZ696 400 mg qd double blind treatment during period 1, Valsartan 320 mg qd during wash-out, and Valsartan 320 mg qd double blind treatment during period 2. Valsartan to LCZ696 - HF Cohort Valsartan Participants in this arm received Valsartan 160 mg twice daily bid during open-label run-in, Valsartan 160 mg bid during period 1, Valsartan 160 mg bid during wash-out, and LCZ696 200 mg bid double blind treatment during period 2.
- Primary Outcome Measures
Name Time Method 24-hour Urinary Sodium Excretion day 1 Urine was collected in 12-hour intervals, and of each pooled 24-hour (daily) sample, sodium concentration was measured. The measure type used for this outcome measure (OM) was Geometric Least square Means (LSM).
Cumulative 7-day Urinary Sodium Excretion 7 day-cummulative (days 1 through 7) Urine was collected in 12-hour intervals, and of each pooled 24-hour (daily) sample, sodium concentration was measured. The measure type used for this outcome measure (OM) was Geometric Least square Means (LSM).
- Secondary Outcome Measures
Name Time Method Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker 2, 4, 6 and 12 hours post dose on day 1; 24 hours post dose on day 2; 2, 4, 6 and 12 hours post dose on day 7 MR-proANP was analyzed at a central laboratory.
Percent Change From Baseline in Mid-regional Pro-adrenomedullin (MR-proADM) Biomarker 2, 4, 6 and 12 hours post dose on day 1; 24 hours post dose on day 2; 0, 4, 6 and 12 hours post dose on day 7 MR-proADM was analyzed at a central laboratory.
Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker 2, 4, 6 and 12 hours post dose on day 1; 24 hours post dose on day 2; 0, 4, 6 and 12 hours post dose on day 7 NT-proBNP was analyzed at a central laboratory.
Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker 0.5, 1, 2, 4, 6 and 12 hours post dose on day 1; 24 hours post dose on day 2; 0, 4, 6 and 12 hours post dose on day 7 BNP was analyzed at a central laboratory.
Percent Change From Baseline in C-terminal-proendothelin-1 (CT-proET-1) Biomarker 12 hours post dose on day 1; 24 hours post dose on day 2; 0 and 12 hours post dose on day 7 CT-proET-1 was analyzed at a central laboratory.
24-hour Diuresis day 1 Urine was collected in 12-hour intervals, and of each pooled 24-hour (daily) sample, urine volume was measured. The measure type used for this OM was Geometric LSM.
7-day Cumulative Diuresis 7-day cumulative (days 1 through 7) Urine was collected in 12-hour intervals, and of each pooled 24-hour (daily) sample, urine volume was measured. The measure type used for this OM was Geometric LSM.
Urinary Cyclic Guanosine Monophosphate (cGMP) Excretion Over 24 Hours day 1, day 6, day 7 cGMP was analyzed at a central laboratory. The measure type used for this OM was Geometric LSM.
Percent Change From Baseline in C-type Natriuretic Peptide (proCNP) Biomarker 2, 4, 6, 8 and 12 hours post dose on day 1; day 2; 0, 4, 6, 8 and 12 hours post dose on day 7 ProCNP was analyzed at a central laboratory.
Percent Change From Baseline in Aldosterone Biomarker 6 and 12 hours post dose on day 1; 24 hours post dose on day 2; 0, 6 and 12 hours post dose on day 7 Aldosterone was analyzed at a central laboratory.
Renal Blood Flow (RBF) Over Time 0, 2, 4 and 6 hours post dose on day 1; 0, 2, 4 and 6 hours post dose on day 7 RBF was used as a measure of renal function.
Supine Systolic Blood Pressure 0, 0.5, 1, 2, 4, 8 and 12 hours post dose on day 1; day 2; 0, 0.5, 1, 2, 4, 8 and 12 hours post dose on day 7 Systolic blood pressure measurements were taken.
Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium) 2, 4, 6 and 12 hours post dose on day 1; 24 hours post dose on day 2; 0, 4, 6 and 12 hours post dose on day 7 Urine was collected in 12-hour intervals, and of each pooled 24-hour (daily) sample, sodium, potassium, albumin and calcium were measured.
Percent Change From Baseline in Blood Plasma Creatinine 4, 6 and 12 hours post dose on day 1; 24 hours post dose on day 2; 0, 4, 6 and 12 hours post dose on day 7 Blood plasma creatinine was analyzed at a central laboratory.
Glomerular Filtration Rate (GFR) Over Time 0, 2, 4 and 6 hours post dose on day 1; 0, 2, 4 and 6 hours post dose on day 7 GFR was used as a measure of renal function.
Supine Diastolic Blood Pressure 0, 0.5, 1, 2, 4, 8 and 12 hours post dose on day 1; day 2; 0, 0.5, 1, 2, 4, 8 and 12 hours post dose on day 7 Diastolic blood pressure measurements were taken.
Supine Pulse Rate 0, 0.5, 1, 2, 4, 8 and 12 hours post dose on day 1; day 2; 0, 0.5, 1, 2, 4, 8 and 12 hours post dose on day 7 Pulse rate measurements were taken.
Trial Locations
- Locations (1)
Novartis Investigative Site
🇷🇺Moscow, Russian Federation