Efficacy and Safety of LCZ696A in Patients With Essential Hypertension

Hypertension Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00549770
• Other study ID #: CLCZ696A2201
• Status: Completed
• Phase: Phase 2
• First received: October 5, 2007
• Last updated: August 11, 2015
• Start date: September 2007
• Est. completion date: July 2008

Study information

• Verified date: August 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaCanada: Health CanadaDenmark: Danish Health AuthoritiesFinland: Finnish Medicines AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesHungary: National Institute of PharmacyItaly: The Italian Medicines AgencyLatvia: State Agency of MedicinesLithuania: State Medicine Control Agency - Ministry of HealthNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Poland: The Central Register of Clinical TrialsRussia: Ministry of Health of the Russian FederationSlovakia: State Institute for Drug ControlSpain: Spanish Agency of MedicinesSweden: Medical Products AgencyTaiwan: Department of Health
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1334
• Est. completion date: July 2008
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertension

Intervention

Drug:
• LCZ696

• Valsartan

• AHU377

• Placebo

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Corrientes
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Canada	Novartis Investigative Site	Cambridge	Ontario
Canada	Novartis Investigative Site	Granby	Quebec
Canada	Novartis Investigative Site	Longueil	Quebec
Canada	Novartis Investigative Site	Mississauga	Ontario
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Saskatoon	Saskatchewan
Canada	Novartis Investigative Site	Sherbrooke	Quebec
Canada	Novartis Investigative Site	Ste-Foy	Quebec
Canada	Novartis Investigative Site	Toronto	Ontario
Denmark	Novartis Investigative Site	Aalborg
Denmark	Novartis Investigative Site	Aalborg SV
Denmark	Novartis Investigative Site	Espergærde
Denmark	Novartis Investigative Site	Greve
Denmark	Novartis Investigative Site	Roslev
Denmark	Novartis Investigative Site	Vaerloese
Denmark	Novartis Investigative Site	Viborg
Finland	Novartis Investigative Site	Helsinki
Finland	Novartis Investigative Site	Helsinki
Finland	Novartis Investigative Site	Helsinki
Finland	Novartis Investigative Site	Kerava
Finland	Novartis Investigative Site	Oulu
Finland	Novartis Investigative Site	Tampere
France	Novartis Investigative Site	Bourges
France	Novartis Investigative Site	La Chapelle sur Erdre
France	Novartis Investigative Site	La Roche sur Yon
France	Novartis Investigative Site	Le Pradet
France	Novartis Investigative Site	Murs Erigné
France	Novartis Investigative Site	Saint Avertin
France	Novartis Investigative Site	Tours
France	Novartis Investigative Site	Vihiers
Germany	Novartis Investigative Site	Balve
Germany	Novartis Investigative Site	Beckingen
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Einbeck
Germany	Novartis Investigative Site	Erfurt
Germany	Novartis Investigative Site	Giengen
Germany	Novartis Investigative Site	Hagen
Germany	Novartis Investigative Site	Haigerloch
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Kassel
Germany	Novartis Investigative Site	Krefeld
Germany	Novartis Investigative Site	Mahlberg
Germany	Novartis Investigative Site	Messkirch
Germany	Novartis Investigative Site	Reinfeld
Germany	Novartis Investigative Site	Siegen
Germany	Novartis Investigative Site	Wallerfing
Germany	Novartis Investigative Site	Warendorf
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Esztergom
Hungary	Novartis Investigative Site	Miskolc
Hungary	Novartis Investigative Site	Nyiregyháza
Italy	Novartis Investigative Site	Caserta	CE
Italy	Novartis Investigative Site	Casorate Primo	PV
Italy	Novartis Investigative Site	Cona	FE
Italy	Novartis Investigative Site	Firenze	FI
Italy	Novartis Investigative Site	Mercato San Severino	SA
Italy	Novartis Investigative Site	Padova	PD
Italy	Novartis Investigative Site	Palermo	PA
Italy	Novartis Investigative Site	Pavia	PV
Italy	Novartis Investigative Site	Pisa	PI
Italy	Novartis Investigative Site	Pisa	PI
Italy	Novartis Investigative Site	Pozzilli	IS
Italy	Novartis Investigative Site	Rozzano	MI
Italy	Novartis Investigative Site	San Daniele Del Friuli	UD
Italy	Novartis Investigative Site	Sassari	SS
Italy	Novartis Investigative Site	Stradella	PV
Italy	Novartis Investigative Site	Vibo Valentia	VV
Italy	Novartis Investigative Site	Vimercate	MI
Latvia	Novartis Investigative Site	Daugavplis
Latvia	Novartis Investigative Site	Kuldiga
Latvia	Novartis Investigative Site	Ogre
Latvia	Novartis Investigative Site	Riga
Latvia	Novartis Investigative Site	Riga
Latvia	Novartis Investigative Site	Riga
Lithuania	Novartis Investigative Site	Alytus
Lithuania	Novartis Investigative Site	Kaunas
Lithuania	Novartis Investigative Site	Kaunas
Lithuania	Novartis Investigative Site	Kaunas
Lithuania	Novartis Investigative Site	Klaipeda
Netherlands	Novartis Investigative Site	Den Bosch
Netherlands	Novartis Investigative Site	Deurne
Netherlands	Novartis Investigative Site	Ermelo
Netherlands	Novartis Investigative Site	Hoogwoud
Netherlands	Novartis Investigative Site	Leeuwarden
Netherlands	Novartis Investigative Site	Losser
Netherlands	Novartis Investigative Site	Oude Pekela
Netherlands	Novartis Investigative Site	Poortvliet
Netherlands	Novartis Investigative Site	Wamel
Poland	Novartis Investigative Site	Olawa
Poland	Novartis Investigative Site	Ostrow Wielkopolski
Poland	Novartis Investigative Site	Tarnow
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	S.-Petersburg
Russian Federation	Novartis Investigative Site	S.-Petersburg
Russian Federation	Novartis Investigative Site	Saint Petersburg
Russian Federation	Novartis Investigative Site	Saint-Petersburg
Russian Federation	Novartis Investigative Site	Saint-Petersburg
Russian Federation	Novartis Investigative Site	Sankt-Peterburg
Slovakia	Novartis Investigative Site	Banska Bystrica	Slovak Republic
Slovakia	Novartis Investigative Site	Bratislava	Slovak Republic
Slovakia	Novartis Investigative Site	Dunajska Streda
Slovakia	Novartis Investigative Site	Nitra	Slovak Republic
Slovakia	Novartis Investigative Site	Presov	Slovak Republic
Slovakia	Novartis Investigative Site	Zilina
Spain	Novartis Investigative Site	Alicante	Comunidad Valenciana
Spain	Novartis Investigative Site	Badalona	Cataluña
Spain	Novartis Investigative Site	Barcelona	Cataluña
Spain	Novartis Investigative Site	Barcelona	Cataluña
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Begonte	Galicia
Spain	Novartis Investigative Site	Benidorm	Comunidad Valenciana
Spain	Novartis Investigative Site	Hospitalet de Llbregat
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Palma de Mallorca	Baleares
Spain	Novartis Investigative Site	Petrel
Spain	Novartis Investigative Site	Quart de Poblet	Comunidad Valenciana
Spain	Novartis Investigative Site	Riudecols
Spain	Novartis Investigative Site	Santiago de Compostela	Galicia
Spain	Novartis Investigative Site	Sevilla	Andalucia
Spain	Novartis Investigative Site	Tarrega	Cataluña
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Spain	Novartis Investigative Site	Vic	Cataluña
Sweden	Novartis Investigative Site	Arvidsjaur
Sweden	Novartis Investigative Site	Boden
Sweden	Novartis Investigative Site	Karlstad
Sweden	Novartis Investigative Site	Kil
Sweden	Novartis Investigative Site	Kristianstad
Sweden	Novartis Investigative Site	Lund
Sweden	Novartis Investigative Site	Skellefteå
Taiwan	Novartis Investigative Site	Changhua
Taiwan	Novartis Investigative Site	Taichung	Taiwan ROC
Taiwan	Novartis Investigative Site	Taichung County
Taiwan	Novartis Investigative Site	Tainan 704	Taiwan ROC
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei
United States	Novartis Investigative Site	Augusta	Georgia
United States	Novartis Investigative Site	Baton Rouge	Louisiana
United States	Novartis Investigative Site	Birmingham	Alabama
United States	Novartis Investigative Site	Brooklyn Center	Minnesota
United States	Novartis Investigative Site	Buena Park	California
United States	Novartis Investigative Site	Chandler	Arizona
United States	Novartis Investigative Site	Charleston	West Virginia
United States	Novartis Investigative Site	Chelsea	Michigan
United States	Novartis Investigative Site	Chicago	Illinois
United States	Novartis Investigative Site	Chicago	Illinois
United States	Novartis Investigative Site	Cincinnati	Ohio
United States	Novartis Investigative Site	Cincinnati	Ohio
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Fair Oaks	California
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Jacksonville	Florida
United States	Novartis Investigative Site	Lake Jackson	Texas
United States	Novartis Investigative Site	Long Beach	California
United States	Novartis Investigative Site	Los Angeles	California
United States	Novartis Investigative Site	Metairie	Louisiana
United States	Novartis Investigative Site	Muscle Shoals	Alabama
United States	Novartis Investigative Site	Oklahoma City	Oklahoma
United States	Novartis Investigative Site	Orangevale	California
United States	Novartis Investigative Site	Pembroke Pines	Florida
United States	Novartis Investigative Site	Pembroke Pines	Florida
United States	Novartis Investigative Site	Pensacola	Florida
United States	Novartis Investigative Site	Peoria	Illinois
United States	Novartis Investigative Site	Richmond	Virginia
United States	Novartis Investigative Site	Royal Oak	Michigan
United States	Novartis Investigative Site	Santa Ana	California
United States	Novartis Investigative Site	Simpsonville	South Carolina
United States	Novartis Investigative Site	St. Peters	Missouri
United States	Novartis Investigative Site	Stockton	California
United States	Novartis Investigative Site	Toms River	New Jersey
United States	Novartis Investigative Site	Trenton	New Jersey
United States	Novartis Investigative Site	Tustin	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Canada,  Denmark,  Finland,  France,  Germany,  Hungary,  Italy,  Latvia,  Lithuania,  Netherlands,  Poland,  Russian Federation,  Slovakia,  Spain,  Sweden,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)	Sitting BP measurements were performed at screening through the end of the study at every study visit. A negative change from baseline indicates improvement.	baseline, week 8	No
Secondary	Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)	Sitting BP measurements were performed at screening through the end of the study at every study visit.	baseline, week 8	No
Secondary	Change From Baseline in 24-hour Mean Ambulatory DBP (maDBP) and maSBP	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.	baseline, 8 weeks	No
Secondary	Change From Baseline in Daytime maDBP and maSBP	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.	baseline, 8 weeks	No
Secondary	Change From Baseline in Nighttime maDBP and maSBP	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.	baseline, 8 weeks	No
Secondary	Percentage of Participants Who Achieved a Successful Response in msDBP	Successful response in msDBP is defined as msDBP <90 mmHg or a reduction = 10 mmHg from baseline.	8 weeks	No
Secondary	Percentage of Participants Who Achieved a Successful Response in msSBP	Successful response in msSBP is defined as msSBP <140 mmHg or a reduction = 20 mmHg from baseline.	8 weeks	No
Secondary	Percentage of Participants Who Achieved Successful Control in msDBP	Successful control in msDBP is defined as msDBP <90 mmHg.	8 weeks	No
Secondary	Percentage of Participants Who Achieved Successful Control in msSBP	Successful control in msSBP is defined as <140 mmHg.	8 weeks	No