Sodium Excretion of LCZ696 in Patients With Hypertension; Heart Failure and Healthy Volunteers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01353508
First received: March 16, 2011
Last updated: October 20, 2015
Last verified: October 2015

March 16, 2011
October 20, 2015
March 2011
August 2012   (final data collection date for primary outcome measure)
  • 24-hour Urinary Sodium Excretion [ Time Frame: day 1 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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).
Comparison of the 24-hour and the cumulative 7-day sodium and urine excretion volume of subjects on LCZ696 compared to subjects on Valsartan or placebo. [ Time Frame: 1 week ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01353508 on ClinicalTrials.gov Archive Site
  • 24-hour Diuresis [ Time Frame: day 1 ] [ Designated as safety issue: No ]
    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 [ Time Frame: 7-day cumulative (days 1 through 7) ] [ Designated as safety issue: No ]
    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 [ Time Frame: day 1, day 6, day 7 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    MR-proANP was analyzed at a central laboratory.
  • Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker [ 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 ] [ Designated as safety issue: No ]
    BNP was analyzed at a central laboratory.
  • Percent Change From Baseline in Mid-regional Pro-adrenomedullin (MR-proADM) Biomarker [ 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 ] [ Designated as safety issue: No ]
    MR-proADM was analyzed at a central laboratory.
  • Percent Change From Baseline in C-type Natriuretic Peptide (proCNP) Biomarker [ 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 ] [ Designated as safety issue: No ]
    ProCNP was analyzed at a central laboratory.
  • Percent Change From Baseline in C-terminal-proendothelin-1 (CT-proET-1) Biomarker [ 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 ] [ Designated as safety issue: No ]
    CT-proET-1 was analyzed at a central laboratory.
  • Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker [ 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 ] [ Designated as safety issue: No ]
    NT-proBNP was analyzed at a central laboratory.
  • Percent Change From Baseline in Aldosterone Biomarker [ 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 ] [ Designated as safety issue: No ]
    Aldosterone was analyzed at a central laboratory.
  • Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium) [ 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    Blood plasma creatinine was analyzed at a central laboratory.
  • Glomerular Filtration Rate (GFR) Over Time [ Time Frame: 0, 2, 4 and 6 hours post dose on day 1; 0, 2, 4 and 6 hours post dose on day 7 ] [ Designated as safety issue: No ]
    GFR was used as a measure of renal function.
  • Renal Blood Flow (RBF) Over Time [ Time Frame: 0, 2, 4 and 6 hours post dose on day 1; 0, 2, 4 and 6 hours post dose on day 7 ] [ Designated as safety issue: No ]
    RBF was used as a measure of renal function.
  • Supine Systolic Blood Pressure [ 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 ] [ Designated as safety issue: No ]
    Systolic blood pressure measurements were taken.
  • Supine Diastolic Blood Pressure [ 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 ] [ Designated as safety issue: No ]
    Diastolic blood pressure measurements were taken.
  • Supine Pulse Rate [ 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 ] [ Designated as safety issue: No ]
    Pulse rate measurements were taken.
  • To compare the cumulative 7-day sodium excretion and urine output with the AUC (Area under the plasma concentration versus time curve) and Cmax (Peak Plasma concentration) of LCZ696 with Valsartan or placebo. [ Time Frame: 1 week ] [ Designated as safety issue: No ]
  • To compare the changes in the biomarkers ANP, BNP and cGMP with the AUC and Cmax of subjects on LCZ696 with Valsartan or placebo. [ Time Frame: 1 week ] [ Designated as safety issue: No ]
  • To assess number of patients with adverse events, abnormal lab values, discontinuation of subjects on LCZ696 versus Valsartan or placebo. [ Time Frame: 1 week ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Sodium Excretion of LCZ696 in Patients With Hypertension; Heart Failure and Healthy Volunteers
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
Assess mechanism of action of LCZ696 related to sodium excretion.
Not Provided
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Hypertension
  • Drug: LCZ696
    200 mg and 400 mg tablets
  • Drug: Valsartan
    160 mg tablets
  • Experimental: 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.
    Interventions:
    • Drug: LCZ696
    • Drug: Valsartan
  • Experimental: 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.
    Interventions:
    • Drug: LCZ696
    • Drug: Valsartan
  • Experimental: 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.
    Interventions:
    • Drug: LCZ696
    • Drug: Valsartan
  • Experimental: 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.
    Interventions:
    • Drug: LCZ696
    • Drug: Valsartan
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
32
August 2012
August 2012   (final data collection date for primary outcome measure)

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
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Russian Federation
 
NCT01353508
CLCZ696B2223
Not Provided
Not Provided
Not Provided
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
October 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP