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
  Purpose
Assess mechanism of action of LCZ696 related to sodium excretion.

Condition Intervention Phase
Hypertension
Drug: LCZ696
Drug: Valsartan
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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).


Secondary Outcome Measures:
  • 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.


Enrollment: 32
Study Start Date: March 2011
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: LCZ696
200 mg and 400 mg tablets
Drug: Valsartan
160 mg tablets
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.
Drug: LCZ696
200 mg and 400 mg tablets
Drug: Valsartan
160 mg tablets
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.
Drug: LCZ696
200 mg and 400 mg tablets
Drug: Valsartan
160 mg tablets
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.
Drug: LCZ696
200 mg and 400 mg tablets
Drug: Valsartan
160 mg tablets

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01353508

Locations
Russian Federation
Novartis Investigative Site
Moscow, Russian Federation, 117198
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01353508     History of Changes
Other Study ID Numbers: CLCZ696B2223 
Study First Received: March 16, 2011
Results First Received: July 15, 2015
Last Updated: October 20, 2015
Health Authority: United States: Food and Drug Administration
Russia: Ministry of Health of the Russian Federation

Keywords provided by Novartis:
Sodium excretion,
LCZ696

Additional relevant MeSH terms:
Hypertension
Cardiovascular Diseases
Vascular Diseases
LCZ 696
Valsartan
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Antihypertensive Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 26, 2016