A Randomized, Double-blind, Controlled, Crossover Study to Evaluate the Sodium Excretion of LCZ696 in Patients With Stable Heart Failure, in Patients With Hypertension, and in Healthy Volunteers
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 32
- Locations
- 1
- Primary Endpoint
- 24-hour Urinary Sodium Excretion
Study Overview
Brief Summary
Assess mechanism of action of LCZ696 related to sodium excretion.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients with heart failure: documented NYHA class II-III heart failure
- •Patients with hypertension: stable hypertensive medication for the preceding 2 months
Exclusion Criteria
- •Women of childbearing potential
- •History of recent myocardial infarction
- •History of dialysis or renal transplant
- •Patients with type 1 diabetes mellitus
Arms & Interventions
LCZ696 to Valsartan - Heart Failure (HF) cohort
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.
Intervention: LCZ696 (Drug)
LCZ696 to Valsartan - Heart Failure (HF) cohort
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.
Intervention: Valsartan (Drug)
Valsartan to LCZ696 - HF Cohort
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.
Intervention: LCZ696 (Drug)
Valsartan to LCZ696 - HF Cohort
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.
Intervention: Valsartan (Drug)
LCZ696 to Valsartan - Hypertension (HTN) cohort
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.
Intervention: LCZ696 (Drug)
LCZ696 to Valsartan - Hypertension (HTN) cohort
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.
Intervention: Valsartan (Drug)
Valsartan to LCZ696 - HTN cohort
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.
Intervention: LCZ696 (Drug)
Valsartan to LCZ696 - HTN cohort
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.
Intervention: Valsartan (Drug)
Outcomes
Primary Outcomes
24-hour Urinary Sodium Excretion
Time Frame: 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
Time Frame: 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 Outcomes
- 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)
- 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)
- 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)
- 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)
- 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)
- 24-hour Diuresis(day 1)
- 7-day Cumulative Diuresis(7-day cumulative (days 1 through 7))
- Urinary Cyclic Guanosine Monophosphate (cGMP) Excretion Over 24 Hours(day 1, day 6, day 7)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)