Back to resultsSodium Excretion of LCZ696 in Patients With Hypertension; Heart Failure and Healthy Volunteers
Primary Purpose
Hypertension
Status
Completed
Phase
Phase 2
Locations
Russian Federation
Study Type
Interventional
Intervention
LCZ696
Valsartan
Sponsored by
About this trial
This is an interventional treatment trial for Hypertension focused on measuring Sodium excretion,, LCZ696
Eligibility Criteria
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
Sites / Locations
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
LCZ696 to Valsartan - Heart Failure (HF) cohort
Valsartan to LCZ696 - HF Cohort
LCZ696 to Valsartan - Hypertension (HTN) cohort
Valsartan to LCZ696 - HTN cohort
Arm Description
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.
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.
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.
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.
Outcomes
Primary Outcome Measures
24-hour Urinary Sodium Excretion
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
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
24-hour Diuresis
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
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
cGMP was analyzed at a central laboratory. The measure type used for this OM was Geometric LSM.
Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker
MR-proANP was analyzed at a central laboratory.
Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker
BNP was analyzed at a central laboratory.
Percent Change From Baseline in Mid-regional Pro-adrenomedullin (MR-proADM) Biomarker
MR-proADM was analyzed at a central laboratory.
Percent Change From Baseline in C-type Natriuretic Peptide (proCNP) Biomarker
ProCNP was analyzed at a central laboratory.
Percent Change From Baseline in C-terminal-proendothelin-1 (CT-proET-1) Biomarker
CT-proET-1 was analyzed at a central laboratory.
Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker
NT-proBNP was analyzed at a central laboratory.
Percent Change From Baseline in Aldosterone Biomarker
Aldosterone was analyzed at a central laboratory.
Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)
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
Blood plasma creatinine was analyzed at a central laboratory.
Glomerular Filtration Rate (GFR) Over Time
GFR was used as a measure of renal function.
Renal Blood Flow (RBF) Over Time
RBF was used as a measure of renal function.
Supine Systolic Blood Pressure
Systolic blood pressure measurements were taken.
Supine Diastolic Blood Pressure
Diastolic blood pressure measurements were taken.
Supine Pulse Rate
Pulse rate measurements were taken.
Full Information
NCT ID
NCT01353508
First Posted
March 16, 2011
Last Updated
October 20, 2015
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT01353508
Brief Title
Sodium Excretion of LCZ696 in Patients With Hypertension; Heart Failure and Healthy Volunteers
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2015
Overall Recruitment Status
Completed
Study Start Date
March 2011 (undefined)
Primary Completion Date
August 2012 (Actual)
Study Completion Date
August 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
5. Study Description
Brief Summary
Assess mechanism of action of LCZ696 related to sodium excretion.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension
Keywords
Sodium excretion,, LCZ696
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
LCZ696 to Valsartan - Heart Failure (HF) cohort
Arm Type
Experimental
Arm Description
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.
Arm Title
Valsartan to LCZ696 - HF Cohort
Arm Type
Experimental
Arm Description
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.
Arm Title
LCZ696 to Valsartan - Hypertension (HTN) cohort
Arm Type
Experimental
Arm Description
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.
Arm Title
Valsartan to LCZ696 - HTN cohort
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
LCZ696
Intervention Description
200 mg and 400 mg tablets
Intervention Type
Drug
Intervention Name(s)
Valsartan
Intervention Description
160 mg tablets
Primary Outcome Measure Information:
Title
24-hour Urinary Sodium Excretion
Description
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).
Time Frame
day 1
Title
Cumulative 7-day Urinary Sodium Excretion
Description
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).
Time Frame
7 day-cummulative (days 1 through 7)
Secondary Outcome Measure Information:
Title
24-hour Diuresis
Description
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.
Time Frame
day 1
Title
7-day Cumulative Diuresis
Description
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.
Time Frame
7-day cumulative (days 1 through 7)
Title
Urinary Cyclic Guanosine Monophosphate (cGMP) Excretion Over 24 Hours
Description
cGMP was analyzed at a central laboratory. The measure type used for this OM was Geometric LSM.
Time Frame
day 1, day 6, day 7
Title
Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker
Description
MR-proANP was analyzed at a central laboratory.
Time Frame
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
Title
Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker
Description
BNP was analyzed at a central laboratory.
Time Frame
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
Title
Percent Change From Baseline in Mid-regional Pro-adrenomedullin (MR-proADM) Biomarker
Description
MR-proADM was analyzed at a central laboratory.
Time Frame
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
Title
Percent Change From Baseline in C-type Natriuretic Peptide (proCNP) Biomarker
Description
ProCNP was analyzed at a central laboratory.
Time Frame
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
Title
Percent Change From Baseline in C-terminal-proendothelin-1 (CT-proET-1) Biomarker
Description
CT-proET-1 was analyzed at a central laboratory.
Time Frame
12 hours post dose on day 1; 24 hours post dose on day 2; 0 and 12 hours post dose on day 7
Title
Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker
Description
NT-proBNP was analyzed at a central laboratory.
Time Frame
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
Title
Percent Change From Baseline in Aldosterone Biomarker
Description
Aldosterone was analyzed at a central laboratory.
Time Frame
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
Title
Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)
Description
Urine was collected in 12-hour intervals, and of each pooled 24-hour (daily) sample, sodium, potassium, albumin and calcium were measured.
Time Frame
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
Title
Percent Change From Baseline in Blood Plasma Creatinine
Description
Blood plasma creatinine was analyzed at a central laboratory.
Time Frame
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
Title
Glomerular Filtration Rate (GFR) Over Time
Description
GFR was used as a measure of renal function.
Time Frame
0, 2, 4 and 6 hours post dose on day 1; 0, 2, 4 and 6 hours post dose on day 7
Title
Renal Blood Flow (RBF) Over Time
Description
RBF was used as a measure of renal function.
Time Frame
0, 2, 4 and 6 hours post dose on day 1; 0, 2, 4 and 6 hours post dose on day 7
Title
Supine Systolic Blood Pressure
Description
Systolic blood pressure measurements were taken.
Time Frame
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
Title
Supine Diastolic Blood Pressure
Description
Diastolic blood pressure measurements were taken.
Time Frame
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
Title
Supine Pulse Rate
Description
Pulse rate measurements were taken.
Time Frame
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Moscow
ZIP/Postal Code
117198
Country
Russian Federation
12. IPD Sharing Statement
Learn more about this trial
Sodium Excretion of LCZ696 in Patients With Hypertension; Heart Failure and Healthy Volunteers
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