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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: October 12, 2015
Last verified: October 2015

August 30, 2012
October 12, 2015
August 2012
October 2013   (final data collection date for primary outcome measure)
Cumulative Sodium Excretion (Natriuresis) at Day 1 [ Time Frame: 0-6 and 0-24 hours on Day 1 ] [ 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 Day 1
  • 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
Complete list of historical versions of study NCT01681576 on ClinicalTrials.gov Archive Site
  • Cumulative Sodium Excretion (Natriuresis) at Day 28 [ Time Frame: 0-6 and 0-24 hours on Day 28 ] [ 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 Day 28
  • Urine Volume (Diuresis) Over Time [ Time Frame: Day -1, Day 1 & Day 28 ] [ Designated as safety issue: No ]
    Urine will be collected and volume measured in fractions of 0 to 6 hours and 0 to 24 hours Day-1, Day 1 and Day 28
  • Seated Office Blood Pressure (BP) (Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)) Over Time [ Time Frame: Day-1, Day 14 and Day 28 ] [ Designated as safety issue: No ]
    Seated Office BP (systolic blood pressure (SBP) and diastolic blood pressure (DBP))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 Sitting Pulse Pressure (PP) Over Time [ Time Frame: Day-1, Day 14 and Day 28 ] [ Designated as safety issue: No ]
    Sitting mean pulse pressure rate was calculated between ambulatory SBP and DBP measurements
  • 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.
Not Provided
Not Provided
 
Assessment of LCZ696 and Valsartan in Asian Patients With Salt-sensitive Hypertension
A Randomized, Double-blind, Crossover Study to Assess the Effects of LCZ696 and Valsartan in Asian Patients With Salt-sensitive Hypertension
This study will evaluate the effect of LCZ696 and valsartan on natriuresis, diuresis, and blood pressure in salt-sensitive Asian hypertensive patients.
Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Salt-sensitive Hypertension
  • Drug: Valsartan
    Valsartan 320mg tablet once daily
  • Drug: LCZ696
    LCZ696 400mg tablet once daily
  • Experimental: LCZ696 followed by Valsartan
    Period 1: LCZ696 400mg QD for 4 weeks then washout followed by Period 2: Valsartan 320mg QD for 4 weeks
    Interventions:
    • Drug: Valsartan
    • Drug: LCZ696
  • Experimental: Valsartan followed by LCZ696
    Period 1: Valsartan 320mg QD for 4 weeks then washout followed by Period 2: LCZ696 400mg QD for 4 weeks
    Interventions:
    • Drug: Valsartan
    • Drug: LCZ696
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
72
October 2013
October 2013   (final data collection date for primary outcome measure)

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

Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Hong Kong,   Korea, Republic of,   Singapore,   Taiwan
 
NCT01681576
CLCZ696A2222
No
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