Assessment of LCZ696 and Valsartan in Asian Patients With Salt-sensitive Hypertension

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01681576
First received: August 30, 2012
Last updated: November 21, 2013
Last verified: November 2013
  Purpose

This study will evaluate the effect of LCZ696 and valsartan on natriuresis, diuresis, and blood pressure in salt-sensitive Asian hypertensive patients.


Condition Intervention Phase
Salt-sensitive Hypertension
Drug: Valsartan
Drug: LCZ696
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Official Title: A Randomized, Double-blind, Crossover Study to Assess the Effects of LCZ696 and Valsartan in Asian Patients With Salt-sensitive Hypertension

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Cumulative Sodium excretion (natriuresis) [ Time Frame: 6 hour following the first dose of LCZ696 and valsartan ] [ Designated as safety issue: No ]
    Urine will be collected in fractions of 0 to 6 hours post-dose. From each fraction, a sample will be drawn for analysis of sodium

  • Cumulative Sodium excretion (natriuresis) [ Time Frame: 24 hour following the first dose of LCZ696 and valsartan ] [ Designated as safety issue: No ]
    Urine will be collected in fractions of 6 to 24 hours post-dose. From each fraction, a sample will be drawn for analysis of sodium


Secondary Outcome Measures:
  • Number of patients with adverse events [ Time Frame: During 4 weeks treatment ] [ Designated as safety issue: Yes ]
    Summarized statistics on adverse events will be reported which will be categorized as total adverse events, serious adverse events and death.

  • Cumulative Sodium excretion (natriuresis) [ Time Frame: After 4 weeks of treatment ] [ Designated as safety issue: No ]
    Urine will be collected in fractions of 0 to 6 hours and 6 to 24 hours post-dose. From each fraction, a sample will be drawn for analysis of sodium

  • Urine Volume (Diuresis) [ Time Frame: During 6 and 24 hours post first dose and after 4 weeks of treatment ] [ Designated as safety issue: No ]
    Urine will be collected and volume measured in fractions of 0 to 6 hours and 6 to 24 hours post-dose first and last dose

  • Pharmacokinetics of LCZ696 (AHU377, LBQ657, valsartan) and Valsartan: Observed maximum plasma concentration (Cmax) following drug administration [ Time Frame: Day 1 and day 28 of treatment ] [ Designated as safety issue: No ]
    Blood will be collected at intervals and plasma separated and analyzed

  • Pharmacokinetics of LCZ696 (AHU377, LBQ657, valsartan) and Valsartan: Time to reach the maximum concentration after drug administration (Tmax) [ Time Frame: Day 1 and day 28 of treatment ] [ Designated as safety issue: No ]
    Blood will be collected at intervals and plasma separated and analyzed

  • Pharmacokinetics of LCZ696 (AHU377, LBQ657, valsartan) and Valsartan:Area under the plasma concentration-time curve from time zero to 24 hours (AUC0-24 hours) [ Time Frame: Day 1 and day 28 of treatment ] [ Designated as safety issue: No ]
    Blood will be collected at intervals and plasma separated and analyzed

  • Pharmacokinetics of LCZ696 and valsartan: Accumulation ratio between Day 28 and Day 1 [ Time Frame: Day 1 and day 28 of treatment ] [ Designated as safety issue: No ]
    Blood will be collected at intervals and plasma separated and analyzed and the ratio AUC-24 hr(Day28) / AUC-24 hr(Day1) calculated

  • Mean seated blood pressure following 4 weeks of treatment [ Time Frame: Day 1 and day 28 of treatment ] [ Designated as safety issue: No ]
    Seating BP (systolic blood pressure (msSBP) and diastolic blood pressure (msDBP))measurements will be performed at trough(immediately prior to dosing at the clinic). Arterial BP readings will be made with an automated BP device.

  • Mean arterial pressure (MAP) after following 4 weeks of treatment [ Time Frame: Day 1 and day 28 of treatment ] [ Designated as safety issue: No ]
    Seating BP (systolic blood pressure (msSBP) and diastolic blood pressure (msDBP))measurements will be performed at trough(immediately prior to dosing at the clinic). Arterial BP readings will be made with an automated BP device.

  • Mean siting pulse pressure after 4 weeks of treatment. [ Time Frame: Day 1 and day 28 of treatment ] [ Designated as safety issue: No ]
    Seating BP (systolic blood pressure (msSBP) and diastolic blood pressure (msDBP))measurements will be performed at trough(immediately prior to dosing at the clinic). Arterial BP readings will be made with an automated BP device.


Enrollment: 72
Study Start Date: August 2012
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Valsartan followed by LCZ696
Period 1: 4 weeks treatment with valsartan, 1-2 weeks wash-out, followed by period 2, 4 weeks treatment with LCZ696
Drug: Valsartan
Valsartan tablet once daily
Drug: LCZ696
LCZ696 tablet once daily
Experimental: LCZ696 followed by Valsartan
Period 1: 4 weeks treatment with LCZ696, 1-2 weeks wash-out, followed by period 2, 4 weeks treatment with valsartan
Drug: Valsartan
Valsartan tablet once daily
Drug: LCZ696
LCZ696 tablet once daily

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Written informed consent must be obtained before any study assessment is performed.
  • Males and females of non-childbearing potential and of legal age (at least 18 years or older as defined by local law).
  • Asian patients with mild to moderate essential hypertension, untreated or currently taking antihypertensive therapy with up to two drugs.

Key Exclusion Criteria:

  • Women of child-bearing potential.
  • History of angioedema, drug-related or otherwise
  • History of hypersensitivity to LCZ696, valsartan, or drugs of similar chemical classes.
  • Severe hypertension (grade 3 of WHO classification; msDBP ≥100 mmHg and/or msSBP ≥ 180 mmHg) at screening or at the end of the washout period.
  • History or evidence of a secondary form of hypertension,
  • Transient ischemic cerebral attack (TIA) during the 12 months prior to screening or any history of stroke.
  • History of myocardial infarction, coronary bypass surgery or percutaneous coronary intervention (PCI) during 12 month prior to screening.
  • Current or history of hypertensive retinopathy.
  • Previous or current diagnosis of heart failure (NYHA Class II-IV).
  • Clinically significant valvular heart disease at screening.

Other protocol defined inclusion/exclusion criteria may apply

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01681576

Locations
United States, California
Novartis Investigative Site
Anaheim, California, United States, 92801
Novartis Investigative Site
Cypress, California, United States, 90630
Novartis Investigative Site
Glendale, California, United States, 91206
Hong Kong
Novartis Investigative Site
Hong Kong, Shatin, NT, Hong Kong
Korea, Republic of
Novartis Investigative Site
Bucheon, Gyeonggi-do, Korea, Republic of, 424-717
Novartis Investigative Site
Koyang-si, Gyeonggi-do, Korea, Republic of, 410-773
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 110 744
Novartis Investigative Site
Seoul, Korea, Republic of, 120-752
Novartis Investigative Site
Seoul, Korea, Republic of, 152-703
Singapore
Novartis Investigative Site
Singapore, Singapore, 168752
Novartis Investigative Site
Singapore, Singapore, 119228
Taiwan
Novartis Investigative Site
Taipei, Taiwan, ROC, Taiwan, 112
Novartis Investigative Site
Taichung, Taiwan, 40447
Novartis Investigative Site
Taipei, Taiwan, 10002
Novartis Investigative Site
Taipei, Taiwan, 114
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01681576     History of Changes
Other Study ID Numbers: CLCZ696A2222
Study First Received: August 30, 2012
Last Updated: November 21, 2013
Health Authority: United States: Food and Drug Administration
Korea: Food and Drug Administration
Taiwan: Department of Health
Singapore: Health Sciences Authority
Hong Kong: Ethics Committee

Keywords provided by Novartis:
hypertension, salt sensitivity, valsartan, LCZ696

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

ClinicalTrials.gov processed this record on April 17, 2014