Efficacy and Safety of LCZ696A in Patients With Essential Hypertension

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00549770
First received: October 5, 2007
Last updated: August 11, 2015
Last verified: August 2015
  Purpose

This study was a dose-ranging efficiacy study in patients with essential hypertension to assess the blood pressure lowering effect, and safety of LCZ696 compared to valsartan and placebo. The study will also evaluate the efficacy and safety of AHU377 as compared to placebo.


Condition Intervention Phase
Hypertension
Drug: LCZ696
Drug: Valsartan
Drug: AHU377
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Multi-center, Randomized, Double-blind, Placebo and Active Controlled, Parallel Group, Dose Range Study to Evaluate the Efficacy and Safety of LCZ696 Comparatively to Valsartan, and to Evaluate AHU377 to Placebo After 8 Week Treatment in Patients With Essential Hypertension

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) [ Time Frame: baseline, week 8 ] [ Designated as safety issue: No ]
    Sitting BP measurements were performed at screening through the end of the study at every study visit. A negative change from baseline indicates improvement.


Secondary Outcome Measures:
  • Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) [ Time Frame: baseline, week 8 ] [ Designated as safety issue: No ]
    Sitting BP measurements were performed at screening through the end of the study at every study visit.

  • Change From Baseline in 24-hour Mean Ambulatory DBP (maDBP) and maSBP [ Time Frame: baseline, 8 weeks ] [ Designated as safety issue: No ]
    Hourly mean ambulatory DBP and SBP post-dosing was calculated for each post-dosing hour over 24 hours by taking the average of the readings taken in the corresponding post-dosing hour at randomization and at week 8.

  • Change From Baseline in Daytime maDBP and maSBP [ Time Frame: baseline, 8 weeks ] [ Designated as safety issue: No ]
    Hourly mean ambulatory DBP and SBP post-dosing was calculated for each post-dosing hour over 24 hours by taking the avergae of the readings taken in the corresponding post-dosing hour at randomization and at week 8. Daytime mean SBP and DBP were the averages of the hourly means between 6 am and 10 pm.

  • Change From Baseline in Nighttime maDBP and maSBP [ Time Frame: baseline, 8 weeks ] [ Designated as safety issue: No ]
    Hourly mean ambulatory DBP and SBP post-dosing was calculated for each post-dosing hour over 24 hours by taking the average of the readings taken in the corresponding post-dosing hour at randomization and at week 8. Nighttime mean SBP and DBP were the averages of the hourly means between 10 pm and 6 am.

  • Percentage of Participants Who Achieved a Successful Response in msDBP [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Successful response in msDBP is defined as msDBP <90 mmHg or a reduction ≥ 10 mmHg from baseline.

  • Percentage of Participants Who Achieved a Successful Response in msSBP [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Successful response in msSBP is defined as msSBP <140 mmHg or a reduction ≥ 20 mmHg from baseline.

  • Percentage of Participants Who Achieved Successful Control in msDBP [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Successful control in msDBP is defined as msDBP <90 mmHg.

  • Percentage of Participants Who Achieved Successful Control in msSBP [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Successful control in msSBP is defined as <140 mmHg.


Enrollment: 1334
Study Start Date: September 2007
Study Completion Date: July 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LCZ696 100 mg
Participants received LCZ696 100 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
Drug: LCZ696 Drug: Placebo
Experimental: LCZ696 200 mg
Participants received LCZ696 200 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
Drug: LCZ696 Drug: Placebo
Experimental: LCZ696 400 mg
Participants received LCZ696 400 mg (200 mg LCZ696 for one week and then up-titration to 400 mg LCZ696 for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
Drug: LCZ696 Drug: Placebo
Active Comparator: Valsartan 80 mg
Participants received Valsartan 80 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
Drug: Valsartan Drug: Placebo
Active Comparator: Valsartan 160 mg
Participants received Valsartan 160 mg and matching placebo to LCZ696, Valsatan and AHU377 (5 tablets and 2 capsules) daily.
Drug: Valsartan Drug: Placebo
Active Comparator: Valsartan 320 mg
Participants received Valsartan 320 mg (160 mg valsartan capsules for one week followed by 320 mg valsartan capsules for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
Drug: Valsartan Drug: Placebo
Experimental: AHU377 200 mg
Participants received AHU377 200 mg and matching placebo to LCZ696 and Valsartan (5 tablets and 2 capsules) daily.
Drug: AHU377 Drug: Placebo
Placebo Comparator: Placebo
Participants received matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
Drug: Placebo

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or females from 18 up to and including 75 years
  • Patients with mild-to-moderate uncomplicated essential hypertension, untreated or currently taking antihypertensive therapy (monotherapy or combination therapy of 2 drugs; therapy with a fixed dose combination of two active substances represents 2 drugs)
  • Untreated patients must have had an office msDBP≥ 95 mmHg at the randomization visit (Visit 3) and the 2 preceding visits (Visits 1 and 2).
  • Treated patients must have had an office msDBP≥ 90 mmHG after washout (Visit 2), and a msDBP> 95 mmHg at baseline (Visit 3);

Exclusion Criteria:

  • Severe hypertension (msSBP ≥180 mmHg and/or msDBP ≥110 mmHg)
  • History of angioedema, drug-related or otherwise, as reported by the patient
  • Type 1 or Type 2 diabetes mellitus (according to the ADA criteria)
  • History or evidence of a secondary form of hypertension, such as renal parenchymal hypertension, renovascular hypertension, coarctation of the aorta, primary hyperaldosteronism, Cushing's disease, drug-induced hypertension, unilateral or bilateral renal artery stenosis, pheochromocytoma, polycystic kidney disease, etc.
  • History of angina pectoris, myocardial infarction, coronary bypass surgery, ischemic heart disease, surgical or percutaneous arterial intervention of any kind (coronary, carotid or peripheral intervention), stroke, TIA (transient ischemic attack), carotid artery stenosis, aortic aneurysm or peripheral arterial disease
  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: NCT00549770

  Show 182 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Study Chair: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00549770     History of Changes
Other Study ID Numbers: CLCZ696A2201
Study First Received: October 5, 2007
Results First Received: August 10, 2012
Last Updated: August 11, 2015
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Canada: Health Canada
Denmark: Danish Health Authorities
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Italy: The Italian Medicines Agency
Latvia: State Agency of Medicines
Lithuania: State Medicine Control Agency - Ministry of Health
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Poland: The Central Register of Clinical Trials
Russia: Ministry of Health of the Russian Federation
Slovakia: State Institute for Drug Control
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Taiwan: Department of Health

Keywords provided by Novartis:
Hypertension, valsartan, LCZ696

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

ClinicalTrials.gov processed this record on August 27, 2015