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

NCT01353508 | Completed Phase 2 Results

• 1 other identifier: CLCZ696B2223
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Assess mechanism of action of LCZ696 related to sodium excretion.

Conditions

Hypertension

Keywords

Sodium excretion,; LCZ696

Outcome Measures

Primary Outcomes (2)

• 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).

  day 1

• 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).

  7 day-cummulative (days 1 through 7)

Secondary Outcomes (17)

• 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 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 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

Study Arms (4)

LCZ696 to Valsartan - Heart Failure (HF) cohort

EXPERIMENTAL

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; Drug: Valsartan

Valsartan to LCZ696 - HF Cohort

EXPERIMENTAL

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; Drug: Valsartan

LCZ696 to Valsartan - Hypertension (HTN) cohort

EXPERIMENTAL

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; Drug: Valsartan

Valsartan to LCZ696 - HTN cohort

EXPERIMENTAL

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; Drug: Valsartan

Interventions

LCZ696 DRUG

200 mg and 400 mg tablets

LCZ696 to Valsartan - Heart Failure (HF) cohort; LCZ696 to Valsartan - Hypertension (HTN) cohort; Valsartan to LCZ696 - HF Cohort; Valsartan to LCZ696 - HTN cohort

Valsartan DRUG

160 mg tablets

LCZ696 to Valsartan - Heart Failure (HF) cohort; LCZ696 to Valsartan - Hypertension (HTN) cohort; Valsartan to LCZ696 - HF Cohort; Valsartan to LCZ696 - HTN cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with heart failure: documented NYHA class II-III heart failure
• Patients with hypertension: stable hypertensive medication for the preceding 2 months

You may not qualify if:

• Women of childbearing potential
• History of recent myocardial infarction
• History of dialysis or renal transplant
• Patients with type 1 diabetes mellitus

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (1)

Novartis Investigative Site

Moscow, 117198, Russia

Location

MeSH Terms

Conditions

Hypertension

Interventions

sacubitril and valsartan sodium hydrate drug combination; Valsartan

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential

Limitations and Caveats

Regarding LSM = 1218.56 for LCZ696 HTN cohort arm at Day 1, 1.0 hr post dose, the value was heavily inflated due to one participant with a very high change from baseline.

Results Point of Contact

• Title: Study Director
• Organization: Novartis

862-778-1873

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2011
• First Posted: May 13, 2011
• Study Start: March 1, 2011
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: November 23, 2015
• Results First Posted: November 23, 2015

Record last verified: 2015-10

Locations

RU (1)