Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints (Core and Extension Phases)

Type 2 Diabetes Mellitus Clinical Trial

— ALTITUDE  

Official title:

A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Determine Whether, in Patients With Type 2 Diabetes at High Risk for Cardiovascular and Renal Events, Aliskiren, on Top of Conventional Treatment, Reduces Cardiovascular and Renal Morbidity and Mortality

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00549757
• Other study ID #: CSPP100E2337
• Secondary ID: 2007-000860-25
• Status: Terminated
• Phase: Phase 3
• First received: October 24, 2007
• Last updated: April 1, 2014
• Start date: October 2007
• Est. completion date: February 2013

Study information

• Verified date: April 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaAustria: Federal Office for Safety in Health CareBelgium: Federal Agency for Medicinal Products and Health ProductsBrazil: Ministry of HealthCanada: Health CanadaChina: Food and Drug AdministrationColombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y AlimentosCzech Republic: State Institute for Drug ControlDenmark: Danish Medicines AgencyFinland: Finnish Medicines AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesGreece: National Organization of MedicinesGuatemala: Ministry of Public Health and Social AssistanceHungary: National Institute of PharmacyIndia: Central Drugs Standard Control OrganizationItaly: National Institute of HealthJapan: Pharmaceuticals and Medical Devices AgencyKorea: Food and Drug AdministrationLithuania: State Medicine Control Agency - Ministry of HealthNetherlands: Medicines Evaluation Board (MEB)Norway: Norwegian Medicines AgencyPeru: General Directorate of Pharmaceuticals, Devices, and DrugsPortugal: National Pharmacy and Medicines InstituteSingapore: Center for Drug AdministrationSlovakia: State Institute for Drug ControlSouth Africa: Medicines Control CouncilSpain: Spanish Agency of MedicinesSweden: Medical Products AgencySwitzerland: SwissmedicTaiwan: Department of HealthThailand: Ministry of Public HealthTurkey: General Directorate of Pharmaceuticals and PharmacyUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyVenezuela: Ministry of Health and Social Development
• Study type: Interventional

Clinical Trial Summary

The purpose of this study was to determine whether, in patients with type 2 diabetes and pre-existing disease of the heart and the circulatory system and/or the kidney, aliskiren at a target dose of 300 mg once daily (compared to placebo), on top of conventional treatment, reduces death and disease caused by the heart, the circulatory system and the kidney.

AMENDMENT 4 RATIONALE (MARCH 2012) :

Protocol amendment 4 served to address the data monitoring committee recommendation dated 14 Dec 2011 to discontinue study treatment in all participating patients. It also addressed the subsequent Health Authorities request to implement a 12 month safety follow-up period (actual duration was 9 months in average) post study drug discontinuation.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 8606
• Est. completion date: February 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 35 Years and older

Eligibility

Inclusion Criteria:

• Type 2 diabetes and at least one of the following:

• Macroalbuminuria and an eGFR =30 mL/min/1.73 m2

• Microalbuminuria and a reduced kidney function (eGFR eGFR =30 and <60 mL/min/1.73 m2)

• A history of CV disease (previous MI, previous stroke, heart failure, coronary artery disease, history of percutaneous coronary intervention, angiography proven stenosis =50% in at least one coronary artery and a reduced kidney function (eGFR =30 and <60 mL/min/1.73 m2)

• Concomitant treatment should follow national guidelines and must include either an Angiotensin-converting-enzyme-inhibitor (ACEi) or an Angiotensin-receptor-blocker (ARB) but not both.

Exclusion Criteria:

• Type 1 diabetes mellitus

• Cardiovascular event or procedure = 3 months prior to Visit 1

• Unstable serum creatinine

• Hypertension: Mean sitting systolic blood pressure (msSBP) = 135 and < 170 mmHg or Mean sitting diastolic blood pressure (msDBP) = 85 and < 110 mmHg unless treated with at least 3 anti-hypertensive medications

• Hypertension msSBP = 170 or msDBP = 110 mmHg

• Baseline Serum Potassium > 5.0 mmol/L

• Patients who are treated with two renin-angiotensin-aldosterone-system-blockers

• Patients with NYHA class III or IV heart failure

• Known renal artery stenosis

• Previous randomization into the AVOID trial (CSPP100C2201)

EXCLUSION SPECIFIC TO THE SAFETY FOLLOW-UP PERIOD:

• Aliskiren or aliskiren containing fixed combination products must not be used

Other protocol-defined inclusion/exclusion criteria applied

Study Design

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

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Aliskiren
Aliskiren 150 mg film-coated tablets
• Placebo
Placebo to match aliskiren 150 mg film-coated tablets

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Buenos aires
Argentina	Novartis Investigative Site	Buenos Aires
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	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Cordoba
Argentina	Novartis Investigative Site	Cordoba
Argentina	Novartis Investigative Site	Cordoba
Argentina	Novartis Investigative Site	Cordoba
Argentina	Novartis Investigative Site	Cordoba
Argentina	Novartis Investigative Site	Cordoba
Argentina	Novartis Investigative Site	Cordoba
Argentina	Novartis Investigative Site	Cordoba
Argentina	Novartis Investigative Site	Corrientes
Argentina	Novartis Investigative Site	Florida	Buenos Aires
Argentina	Novartis Investigative Site	Lanus	Buenos Aires
Argentina	Novartis Investigative Site	Ramos Mejia	Buenos Aires
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	Santa Fe
Argentina	Novartis Investigative Site	Santa Fe
Argentina	Novartis Investigative Site	Santa Fe
Argentina	Novartis Investigative Site	Zarate	Buenos Aires
Austria	Novartis Investigative Site	Bregenz
Austria	Novartis Investigative Site	Feldkirch
Austria	Novartis Investigative Site	Graz
Austria	Novartis Investigative Site	Innsbruck
Austria	Novartis Investigative Site	Salzburg
Austria	Novartis Investigative Site	Vienna
Austria	Novartis Investigative Site	Wien
Austria	Novartis Investigative Site	Wien
Austria	Novartis Investigative Site	Wien
Belgium	Novartis Investigative Site	Bonheiden
Belgium	Novartis Investigative Site	Brugge
Belgium	Novartis Investigative Site	Brussel
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Charleroi
Belgium	Novartis Investigative Site	De Pinte
Belgium	Novartis Investigative Site	Edegem
Belgium	Novartis Investigative Site	Genk
Belgium	Novartis Investigative Site	Gent
Belgium	Novartis Investigative Site	Hasselt
Belgium	Novartis Investigative Site	Kortrijk
Belgium	Novartis Investigative Site	La Louvière
Belgium	Novartis Investigative Site	Leuven
Belgium	Novartis Investigative Site	Liege
Belgium	Novartis Investigative Site	Roeselare
Belgium	Novartis Investigative Site	Ronse
Belgium	Novartis Investigative Site	Seraing
Belgium	Novartis Investigative Site	Sint-Gillis-Waas
Belgium	Novartis Investigative Site	Turnhout
Belgium	Novartis Investigative Site	Vilvoorde
Belgium	Novartis Investigative Site	Willebroek
Brazil	Novartis Investigative Site	Belem	PA
Brazil	Novartis Investigative Site	Campinas	SP
Brazil	Novartis Investigative Site	Campinas	SP
Brazil	Novartis Investigative Site	Fortaleza	CE
Brazil	Novartis Investigative Site	Fortaleza	CE
Brazil	Novartis Investigative Site	Juiz de Fora	MG
Brazil	Novartis Investigative Site	Marilia	SP
Brazil	Novartis Investigative Site	Porto Alegre	RS
Brazil	Novartis Investigative Site	Rio de Janeiro	RJ
Brazil	Novartis Investigative Site	Rio de Janeiro	RJ
Brazil	Novartis Investigative Site	Salvador	BA
Brazil	Novartis Investigative Site	Santos	SP
Brazil	Novartis Investigative Site	Sao Jose do Rio Preto	SP
Brazil	Novartis Investigative Site	São Paulo	SP
Brazil	Novartis Investigative Site	São Paulo	SP
Brazil	Novartis Investigative Site	Sorocaba	SP
Brazil	Novartis Investigative Site	Vitoria	ES
Canada	Novartis Investigative Site	Bay Roberts	Newfoundland and Labrador
Canada	Novartis Investigative Site	Brampton	Ontario
Canada	Novartis Investigative Site	Burlington	Ontario
Canada	Novartis Investigative Site	Cambridge	Ontario
Canada	Novartis Investigative Site	Courtice	Ontario
Canada	Novartis Investigative Site	Edmonton	Alberta
Canada	Novartis Investigative Site	Edmonton	Alberta
Canada	Novartis Investigative Site	Etobicoke	Ontario
Canada	Novartis Investigative Site	Greenfield Park	Quebec
Canada	Novartis Investigative Site	London	Ontario
Canada	Novartis Investigative Site	Mirabel	Quebec
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	North Bay	Ontario
Canada	Novartis Investigative Site	Oakville	Ontario
Canada	Novartis Investigative Site	Oshawa	Ontario
Canada	Novartis Investigative Site	Ottawa	Ontario
Canada	Novartis Investigative Site	Ouest-Montreal
Canada	Novartis Investigative Site	Pointe-Claire	Quebec
Canada	Novartis Investigative Site	Québec	Quebec
Canada	Novartis Investigative Site	Sainte-Foy	Quebec
Canada	Novartis Investigative Site	Sainte-Foy	Quebec
Canada	Novartis Investigative Site	Saskatoon	Saskatchewan
Canada	Novartis Investigative Site	Scarborough	Ontario
Canada	Novartis Investigative Site	Sherbrooke	Quebec
Canada	Novartis Investigative Site	St. John's	Newfoundland and Labrador
Canada	Novartis Investigative Site	Ste-Foy	Quebec
Canada	Novartis Investigative Site	Thornhill	Ontario
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Trois-Rivières	Quebec
Canada	Novartis Investigative Site	Vancouver	British Columbia
Canada	Novartis Investigative Site	Winnipeg	Manitoba
Canada	Novartis Investigative Site	Winnipeg	Manitoba
China	Novartis Investigative Site	Beijing	Beijing
China	Novartis Investigative Site	Beijing	Beijing
China	Novartis Investigative Site	Beijing	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Changsha	Hunan
China	Novartis Investigative Site	Changsha City	Hunan
China	Novartis Investigative Site	Chengdu
China	Novartis Investigative Site	Chengdu	Sichuan
China	Novartis Investigative Site	Chongqing
China	Novartis Investigative Site	Chongqing	Chongqing
China	Novartis Investigative Site	Chongqing	Chongqing
China	Novartis Investigative Site	Dalian
China	Novartis Investigative Site	Dalian	Liaoning
China	Novartis Investigative Site	Fuzhou	Fujian
China	Novartis Investigative Site	Guangzhou	Guangdong
China	Novartis Investigative Site	Guangzhou
China	Novartis Investigative Site	Hangzhou	Zhejiang
China	Novartis Investigative Site	Hangzhou	Zhejiang
China	Novartis Investigative Site	Hangzhou	Zhejiang
China	Novartis Investigative Site	Hangzhou	Zhejiang
China	Novartis Investigative Site	Harbin	Heilongjiang
China	Novartis Investigative Site	Harbin	Heilongjiang
China	Novartis Investigative Site	Kunming	Yunnan
China	Novartis Investigative Site	Nanjing	Jiangsu
China	Novartis Investigative Site	Nanjing	Jiangsu
China	Novartis Investigative Site	Nanjing	Jiangsu
China	Novartis Investigative Site	Nanjing	Jiangsu
China	Novartis Investigative Site	Qingdao	Shandong
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shenyang	Liaoning
China	Novartis Investigative Site	Shijiazhuang	Hebei
China	Novartis Investigative Site	Suzhou	Jiangsu
China	Novartis Investigative Site	Tianjin
China	Novartis Investigative Site	Tianjin
China	Novartis Investigative Site	Wuhan	Hubei
China	Novartis Investigative Site	Xi'an	Shanxi
China	Novartis Investigative Site	Xi'an	Shanxi
Colombia	Novartis Investigative Site	Bogotá
Colombia	Novartis Investigative Site	Cali
Colombia	Novartis Investigative Site	Florida Blanca
Colombia	Novartis Investigative Site	Medellín
Czech Republic	Novartis Investigative Site	Brno
Czech Republic	Novartis Investigative Site	Brno-Bohunice
Czech Republic	Novartis Investigative Site	Ceske Budejovice
Czech Republic	Novartis Investigative Site	Ostrava
Czech Republic	Novartis Investigative Site	Pardubice
Czech Republic	Novartis Investigative Site	Pisek
Czech Republic	Novartis Investigative Site	Prague 2
Czech Republic	Novartis Investigative Site	Prague 2
Czech Republic	Novartis Investigative Site	Prague 4 - Krc
Czech Republic	Novartis Investigative Site	Prague 5 - Motol
Denmark	Novartis Investigative Site	Aalborg
Denmark	Novartis Investigative Site	Århus
Denmark	Novartis Investigative Site	Copenhagen NV
Denmark	Novartis Investigative Site	Frederiksberg
Denmark	Novartis Investigative Site	Gentofte
Denmark	Novartis Investigative Site	Hillerød
Denmark	Novartis Investigative Site	Hvidovre
Denmark	Novartis Investigative Site	Roskilde
Denmark	Novartis Investigative Site	Slagelse
Denmark	Novartis Investigative Site	Svendborg
Finland	Novartis Investigative Site	Helsinki
Finland	Novartis Investigative Site	Hyvinkää
Finland	Novartis Investigative Site	Kajaani
Finland	Novartis Investigative Site	Kuopio
Finland	Novartis Investigative Site	Lohja
Finland	Novartis Investigative Site	Oulu
Finland	Novartis Investigative Site	OYS
Finland	Novartis Investigative Site	Pori
Finland	Novartis Investigative Site	Tammisaari
Finland	Novartis Investigative Site	Tampere
Finland	Novartis Investigative Site	Valkeakoski
France	Novartis Investigative Site	Besancon Cedex
France	Novartis Investigative Site	Bondy
France	Novartis Investigative Site	Corbeil Essonnes
France	Novartis Investigative Site	Grenoble
France	Novartis Investigative Site	La Rochelle
France	Novartis Investigative Site	Lagny sur Marne
France	Novartis Investigative Site	Limoges Cedex
France	Novartis Investigative Site	Lyon
France	Novartis Investigative Site	Lyon Cedex 03
France	Novartis Investigative Site	Paris cedex 18
France	Novartis Investigative Site	Paris Cedex 4
France	Novartis Investigative Site	Poitiers Cedex
Germany	Novartis Investigative Site	Aschaffenburg
Germany	Novartis Investigative Site	Aschaffenburg
Germany	Novartis Investigative Site	Asslar
Germany	Novartis Investigative Site	Bad Oeynhausen
Germany	Novartis Investigative Site	Barsinghausen
Germany	Novartis Investigative Site	Bensheim
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Bonn
Germany	Novartis Investigative Site	Bottrop
Germany	Novartis Investigative Site	Bremen
Germany	Novartis Investigative Site	Bretten
Germany	Novartis Investigative Site	Cloppenburg
Germany	Novartis Investigative Site	Dippoldiswalde
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Duesseldorf
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Fuldatal
Germany	Novartis Investigative Site	Göttingen
Germany	Novartis Investigative Site	Hagen
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Heilbronn
Germany	Novartis Investigative Site	Heilbronn
Germany	Novartis Investigative Site	Ingelheim
Germany	Novartis Investigative Site	Jena
Germany	Novartis Investigative Site	Kassel
Germany	Novartis Investigative Site	Krefeld
Germany	Novartis Investigative Site	Magdeburg
Germany	Novartis Investigative Site	Mainz
Germany	Novartis Investigative Site	Messkirch
Germany	Novartis Investigative Site	Muehldorf am Inn
Germany	Novartis Investigative Site	Neuwied
Germany	Novartis Investigative Site	Offenbach
Germany	Novartis Investigative Site	Rehburg-Loccum
Germany	Novartis Investigative Site	Riesa
Germany	Novartis Investigative Site	Schauenburg-Elgershausen
Germany	Novartis Investigative Site	Schwabenheim
Germany	Novartis Investigative Site	St. Ingbert - Oberwuerzbach
Germany	Novartis Investigative Site	Ursensollen
Germany	Novartis Investigative Site	Wetter
Germany	Novartis Investigative Site	Wiehl
Germany	Novartis Investigative Site	Wiesbaden
Germany	Novartis Investigative Site	Wuerzburg
Greece	Novartis Investigative Site	Alexandroupolis
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Athens - GR
Greece	Novartis Investigative Site	Ioannina
Greece	Novartis Investigative Site	Patras
Greece	Novartis Investigative Site	Piraeurs
Greece	Novartis Investigative Site	Thessaloniki
Greece	Novartis Investigative Site	Thessaloniki
Guatemala	Novartis Investigative Site	Guatemala City
Guatemala	Novartis Investigative Site	Guatemala City
Guatemala	Novartis Investigative Site	Guatemala City
Guatemala	Novartis Investigative Site	Guatemala City
Hungary	Novartis Investigative Site	Baja
Hungary	Novartis Investigative Site	Balatonfured
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Debrecen
Hungary	Novartis Investigative Site	Debrecen
Hungary	Novartis Investigative Site	Gyula
Hungary	Novartis Investigative Site	Kaposvar
Hungary	Novartis Investigative Site	Miskolc
Hungary	Novartis Investigative Site	Pecs
Hungary	Novartis Investigative Site	Szeged
Hungary	Novartis Investigative Site	Zalaegerszeg
India	Novartis Investigative Site	Ahmedabad	Gujarat
India	Novartis Investigative Site	Bangalore	Karnataka
India	Novartis Investigative Site	Bangalore
India	Novartis Investigative Site	Banglaore	Karnataka
India	Novartis Investigative Site	Chennai
India	Novartis Investigative Site	Chennai
India	Novartis Investigative Site	Chennai	Tamil Nadu
India	Novartis Investigative Site	Hyderabad
India	Novartis Investigative Site	Hyderabad	Andhra Pradesh, INDIA
India	Novartis Investigative Site	Hyderabad	Andhra Pradesh
India	Novartis Investigative Site	Hyderabad	Andhra Pradesh
India	Novartis Investigative Site	Hyderabad	Andhra Pradesh
India	Novartis Investigative Site	Kochi	Kerala
India	Novartis Investigative Site	Kolkota
India	Novartis Investigative Site	Mangalore	Karnataka
India	Novartis Investigative Site	Mumbai	Maharashtra
India	Novartis Investigative Site	New Delhi
India	Novartis Investigative Site	Pune	Maharashtra
India	Novartis Investigative Site	Pune	Maharashtra
India	Novartis Investigative Site	Vellore	Tamil Nadu
Italy	Novartis Investigative Site	Arenzano	GE
Italy	Novartis Investigative Site	Belluno	BL
Italy	Novartis Investigative Site	Bergamo	BG
Italy	Novartis Investigative Site	Bologna	BO
Italy	Novartis Investigative Site	Campobasso	CB
Italy	Novartis Investigative Site	Caserta	CE
Italy	Novartis Investigative Site	Casorate Primo	PV
Italy	Novartis Investigative Site	Catanzaro	CZ
Italy	Novartis Investigative Site	Cava De' Tirreni	SA
Italy	Novartis Investigative Site	Chieti	CH
Italy	Novartis Investigative Site	Cona	FE
Italy	Novartis Investigative Site	Cosenza	CS
Italy	Novartis Investigative Site	Cuneo	CN
Italy	Novartis Investigative Site	Firenze	FI
Italy	Novartis Investigative Site	Foggia	FG
Italy	Novartis Investigative Site	Genova	GE
Italy	Novartis Investigative Site	Isernia
Italy	Novartis Investigative Site	L'Aquila	AQ
Italy	Novartis Investigative Site	Lecco	LC
Italy	Novartis Investigative Site	Mercato San Severino	SA
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Monza	MB
Italy	Novartis Investigative Site	Napoli
Italy	Novartis Investigative Site	Olbia	SS
Italy	Novartis Investigative Site	Palermo	PA
Italy	Novartis Investigative Site	Parma	PR
Italy	Novartis Investigative Site	Passirana di Rho	MI
Italy	Novartis Investigative Site	Pavia	PV
Italy	Novartis Investigative Site	Perugia	PG
Italy	Novartis Investigative Site	Pisa	PI
Italy	Novartis Investigative Site	Pisa	PI
Italy	Novartis Investigative Site	Pordenone	PN
Italy	Novartis Investigative Site	Pozzilli	IS
Italy	Novartis Investigative Site	Ravenna	RA
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Salerno	SA
Italy	Novartis Investigative Site	San Daniele Del Friuli	UD
Italy	Novartis Investigative Site	Sassari	SS
Italy	Novartis Investigative Site	Siena	SI
Italy	Novartis Investigative Site	Stradella	PV
Italy	Novartis Investigative Site	Torino	TO
Italy	Novartis Investigative Site	Torino	TO
Italy	Novartis Investigative Site	Torino	TO
Italy	Novartis Investigative Site	Udine	UD
Italy	Novartis Investigative Site	Venezia	VE
Italy	Novartis Investigative Site	Verona	VR
Italy	Novartis Investigative Site	Vittorio Veneto	TV
Japan	Novartis Investigative Site	Aira-city	Kagoshima
Japan	Novartis Investigative Site	Asahi	Chiba
Japan	Novartis Investigative Site	Asahikawa	Hokkaido
Japan	Novartis Investigative Site	Bunkyo-ku	Tokyo
Japan	Novartis Investigative Site	Chuo-ku	Tokyo
Japan	Novartis Investigative Site	Isehara-city	Kanagawa
Japan	Novartis Investigative Site	Kasuga	Fukuoka
Japan	Novartis Investigative Site	Kawasaki	Kanagawa
Japan	Novartis Investigative Site	Kitakyushu	Fukuoka
Japan	Novartis Investigative Site	Koriyama-city	Fukushima
Japan	Novartis Investigative Site	Kyoto-city	Kyoto
Japan	Novartis Investigative Site	Kyoto-city	Kyoto
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Ohtsu-city	Shiga
Japan	Novartis Investigative Site	Oita
Japan	Novartis Investigative Site	Oita
Japan	Novartis Investigative Site	Okayama
Japan	Novartis Investigative Site	Okayama-city	Okayama
Japan	Novartis Investigative Site	Sapporo	Hokkaido
Japan	Novartis Investigative Site	Sapporo	Hokkaido
Japan	Novartis Investigative Site	Sapporo-city	Hokkaido
Japan	Novartis Investigative Site	Sendai-city	Miyagi
Japan	Novartis Investigative Site	Shimizu	Shizuoka
Japan	Novartis Investigative Site	Suwa	Nagano
Japan	Novartis Investigative Site	Takamatsu	Kagawa
Japan	Novartis Investigative Site	Takaoka	Toyama
Japan	Novartis Investigative Site	Takatsuki-city	Osaka
Japan	Novartis Investigative Site	Tokorozawa	Saitama
Japan	Novartis Investigative Site	Toride-city	Ibaraki
Japan	Novartis Investigative Site	Toyonaka	Osaka
Japan	Novartis Investigative Site	Yao-city	Osaka
Japan	Novartis Investigative Site	Yatsushiro	Kumamoto
Korea, Republic of	Novartis Investigative Site	Ansan	Gyeonggi-do
Korea, Republic of	Novartis Investigative Site	Anyang	Gyeonggi-do
Korea, Republic of	Novartis Investigative Site	Bundang	Seongnam
Korea, Republic of	Novartis Investigative Site	Busan
Korea, Republic of	Novartis Investigative Site	Daejeon
Korea, Republic of	Novartis Investigative Site	Incheon
Korea, Republic of	Novartis Investigative Site	Pusan
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Taegu
Lithuania	Novartis Investigative Site	Kaunas
Lithuania	Novartis Investigative Site	Klaipeda
Lithuania	Novartis Investigative Site	Vilnius
Lithuania	Novartis Investigative Site	Vilnius
Netherlands	Novartis Investigative Site	Alkmaar
Netherlands	Novartis Investigative Site	Almelo
Netherlands	Novartis Investigative Site	Amersfoort
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Apeldoorn
Netherlands	Novartis Investigative Site	Arnhem
Netherlands	Novartis Investigative Site	Breda
Netherlands	Novartis Investigative Site	Delft
Netherlands	Novartis Investigative Site	Den Helder
Netherlands	Novartis Investigative Site	Deventer
Netherlands	Novartis Investigative Site	Doetinchem
Netherlands	Novartis Investigative Site	Dordrecht
Netherlands	Novartis Investigative Site	Eindhoven
Netherlands	Novartis Investigative Site	Eindhoven
Netherlands	Novartis Investigative Site	Goes
Netherlands	Novartis Investigative Site	Groningen
Netherlands	Novartis Investigative Site	Heerlen
Netherlands	Novartis Investigative Site	Hoogeveen
Netherlands	Novartis Investigative Site	Hoogwoud
Netherlands	Novartis Investigative Site	Losser
Netherlands	Novartis Investigative Site	Meppel
Netherlands	Novartis Investigative Site	Nieuwegein
Netherlands	Novartis Investigative Site	Oude Pekela
Netherlands	Novartis Investigative Site	Rotterdam
Netherlands	Novartis Investigative Site	Rotterdam
Netherlands	Novartis Investigative Site	Rotterdam
Netherlands	Novartis Investigative Site	Tiel
Netherlands	Novartis Investigative Site	Utrecht
Netherlands	Novartis Investigative Site	Venlo
Netherlands	Novartis Investigative Site	Woerden
Netherlands	Novartis Investigative Site	Zwijndrecht
Netherlands	Novartis Investigative Site	Zwolle
Norway	Novartis Investigative Site	Bergen
Norway	Novartis Investigative Site	Fredrikstad
Norway	Novartis Investigative Site	Hønefoss
Norway	Novartis Investigative Site	Horten
Norway	Novartis Investigative Site	Oslo
Norway	Novartis Investigative Site	Skedsmokorset
Norway	Novartis Investigative Site	Skien
Norway	Novartis Investigative Site	Spikkestad
Norway	Novartis Investigative Site	Stavanger
Norway	Novartis Investigative Site	Svelvik
Norway	Novartis Investigative Site	Tønsberg
Norway	Novartis Investigative Site	Tromsø
Norway	Novartis Investigative Site	Trondheim
Peru	Novartis Investigative Site	Bellavista	Lima
Peru	Novartis Investigative Site	Cercado de Lima	Lima
Peru	Novartis Investigative Site	San Borja	Lima
Peru	Novartis Investigative Site	San Isidro	Lima
Peru	Novartis Investigative Site	San Martin de Porres	Lima
Peru	Novartis Investigative Site	Santiago de Surco	Lima
Portugal	Novartis Investigative Site	Almada
Portugal	Novartis Investigative Site	Amadora
Portugal	Novartis Investigative Site	Coimbra
Portugal	Novartis Investigative Site	Linda-a-Velha
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Matosinhos
Portugal	Novartis Investigative Site	Portimão
Portugal	Novartis Investigative Site	Porto
Portugal	Novartis Investigative Site	Santa Maria da Feira
Portugal	Novartis Investigative Site	Santarém
Puerto Rico	Novartis Investigative Site	Ponce
Puerto Rico	Novartis Investigative Site	Ponce
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Slovakia	Novartis Investigative Site	Banksa Bystrica
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Bratislava	Slovak Republic
Slovakia	Novartis Investigative Site	Kosice	Slovak Republic
Slovakia	Novartis Investigative Site	Kosice
Slovakia	Novartis Investigative Site	Lubochna
Slovakia	Novartis Investigative Site	Lucenec
Slovakia	Novartis Investigative Site	Martin
Slovakia	Novartis Investigative Site	Nitra
Slovakia	Novartis Investigative Site	Piestany
Slovakia	Novartis Investigative Site	Prievidza
Slovakia	Novartis Investigative Site	Trstena
Slovakia	Novartis Investigative Site	Zilina	Slovak Republic
South Africa	Novartis Investigative Site	Cape Town
South Africa	Novartis Investigative Site	Durban
South Africa	Novartis Investigative Site	Durban
South Africa	Novartis Investigative Site	Durban
South Africa	Novartis Investigative Site	Durban
South Africa	Novartis Investigative Site	Gauteng
South Africa	Novartis Investigative Site	Johannesburg
South Africa	Novartis Investigative Site	Port Elizabeth
South Africa	Novartis Investigative Site	Pretoria
South Africa	Novartis Investigative Site	Somerset West	Western Cape
Spain	Novartis Investigative Site	Alacuas	Comunidad Valenciana
Spain	Novartis Investigative Site	Alcazar de San Juan	Castilla la Mancha
Spain	Novartis Investigative Site	Alcorcón	Madrid
Spain	Novartis Investigative Site	Alfaro	Rioja
Spain	Novartis Investigative Site	Alicante	Comunidad Valenciana
Spain	Novartis Investigative Site	Alzira	Comunidad Valenciana
Spain	Novartis Investigative Site	Aranda de Duero	Castilla y Leon
Spain	Novartis Investigative Site	Arganda del Rey	Madrid
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Cataluña
Spain	Novartis Investigative Site	Barcelona	Cataluña
Spain	Novartis Investigative Site	Begonte	Galicia
Spain	Novartis Investigative Site	Benidorm	Comunidad Valenciana
Spain	Novartis Investigative Site	Cadiz	Andalucia
Spain	Novartis Investigative Site	Civdad Real	Madrid
Spain	Novartis Investigative Site	Ferrol	Galicia
Spain	Novartis Investigative Site	Girona	Cataluña
Spain	Novartis Investigative Site	Granada	Andalucia
Spain	Novartis Investigative Site	Hospitalet de Llbregat
Spain	Novartis Investigative Site	Hospitalet de Llobregat
Spain	Novartis Investigative Site	Hospitalet de Llobregat	Barcelona
Spain	Novartis Investigative Site	Jerez de La Frontera	Andalucia
Spain	Novartis Investigative Site	La Coruña	Galicia
Spain	Novartis Investigative Site	La Pobla Llarga	Cataluña
Spain	Novartis Investigative Site	Llança	Cataluña
Spain	Novartis Investigative Site	Logroño	Rioja
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Malaga	Andalucia
Spain	Novartis Investigative Site	Malaga	Andalucia
Spain	Novartis Investigative Site	Málaga	Andalucia
Spain	Novartis Investigative Site	Manresa	Cataluña
Spain	Novartis Investigative Site	Mérida	Extremadura
Spain	Novartis Investigative Site	Miranda de Ebro	Castilla y Leon
Spain	Novartis Investigative Site	Mollet del Vallés	Cataluña
Spain	Novartis Investigative Site	Murcia	Madrid
Spain	Novartis Investigative Site	Oviedo	Asturias
Spain	Novartis Investigative Site	Oviedo	Asturias
Spain	Novartis Investigative Site	Oviedo	Asturias
Spain	Novartis Investigative Site	Palma De Mallorca	Islas Baleares
Spain	Novartis Investigative Site	Plentzia	Pais Vasco
Spain	Novartis Investigative Site	Pontevedra	Galicia
Spain	Novartis Investigative Site	Puerto de Sagunto	Comunidad Valenciana
Spain	Novartis Investigative Site	Puerto de Santa Maria	Andalucia
Spain	Novartis Investigative Site	Quart de Poblet	Comunidad Valenciana
Spain	Novartis Investigative Site	Rubi	Cataluña
Spain	Novartis Investigative Site	Sabadell	Barcelona
Spain	Novartis Investigative Site	San Sebastian	Pais Vasco
Spain	Novartis Investigative Site	Sanlúcar de Barrameda	Andalucia
Spain	Novartis Investigative Site	Santa Coloma de Gramanet	Cataluña
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	Valencia	Comunidad Valenciana
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Spain	Novartis Investigative Site	Vic	Cataluña
Spain	Novartis Investigative Site	Vigo	Galicia
Spain	Novartis Investigative Site	Villabona	Pais Vasco
Spain	Novartis Investigative Site	Xixona	Comunidad Valenciana
Spain	Novartis Investigative Site	Zumarraga	Pais Vasco
Sweden	Novartis Investigative Site	Göteborg
Sweden	Novartis Investigative Site	Helsingborg
Sweden	Novartis Investigative Site	Karlstad
Sweden	Novartis Investigative Site	Malmö
Sweden	Novartis Investigative Site	Rättvik
Sweden	Novartis Investigative Site	Stenstorp
Sweden	Novartis Investigative Site	Uppsala
Sweden	Novartis Investigative Site	Varberg
Switzerland	Novartis Investigative Site	Ascona
Switzerland	Novartis Investigative Site	Bern
Switzerland	Novartis Investigative Site	Bolligen
Switzerland	Novartis Investigative Site	Bruderholz
Switzerland	Novartis Investigative Site	Estavayer-le-Lac	CH
Switzerland	Novartis Investigative Site	Fribourg
Switzerland	Novartis Investigative Site	La Chaux-de-Fonds
Switzerland	Novartis Investigative Site	Lausanne
Switzerland	Novartis Investigative Site	Lugano
Switzerland	Novartis Investigative Site	Lugano
Switzerland	Novartis Investigative Site	Renens
Switzerland	Novartis Investigative Site	Schaffhausen
Switzerland	Novartis Investigative Site	St. Gallen
Switzerland	Novartis Investigative Site	Winterthur
Switzerland	Novartis Investigative Site	Zuerich
Taiwan	Novartis Investigative Site	Changhua
Taiwan	Novartis Investigative Site	Kaohsiung
Taiwan	Novartis Investigative Site	Niaosong Township
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Taichung County
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Yungkang	Tainan
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Chiang Mai
Turkey	Novartis Investigative Site	Altunizade
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Gaziantep
Turkey	Novartis Investigative Site	Izmir
Turkey	Novartis Investigative Site	Izmir
Turkey	Novartis Investigative Site	Kocaeli
United Kingdom	Novartis Investigative Site	Bath
United Kingdom	Novartis Investigative Site	Cardiff
United Kingdom	Novartis Investigative Site	Cardiff
United Kingdom	Novartis Investigative Site	Cornwall	England
United Kingdom	Novartis Investigative Site	Crawley	West Sussex
United Kingdom	Novartis Investigative Site	East Horsley	Surrey
United Kingdom	Novartis Investigative Site	Glasgow	Scotland
United Kingdom	Novartis Investigative Site	Glasgow
United Kingdom	Novartis Investigative Site	Glasgow
United Kingdom	Novartis Investigative Site	Gravesend	Kent
United Kingdom	Novartis Investigative Site	High Wycombe	Buckinghamshire
United Kingdom	Novartis Investigative Site	Irvine
United Kingdom	Novartis Investigative Site	Lancashire
United Kingdom	Novartis Investigative Site	Lancashire
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Manchester
United Kingdom	Novartis Investigative Site	Merseyside
United Kingdom	Novartis Investigative Site	Paignton	Devon
United Kingdom	Novartis Investigative Site	Rugby
United Kingdom	Novartis Investigative Site	Truro	Cornwall
United Kingdom	Novartis Investigative Site	Vale of Glanmorgan
United Kingdom	Novartis Investigative Site	Welwyn Garden City,	Hertfordshire
United Kingdom	Novartis Investigative Site	Wrexham
United States	Novartis Investigative Site	Aiken	South Carolina
United States	Novartis Investigative Site	Albany	New York
United States	Novartis Investigative Site	Albuquerque	New Mexico
United States	Novartis Investigative Site	Alexandria	Virginia
United States	Novartis Investigative Site	Allentown	Pennsylvania
United States	Novartis Investigative Site	Amarillo	Texas
United States	Novartis Investigative Site	Ann Arbor	Michigan
United States	Novartis Investigative Site	Appleton	Wisconsin
United States	Novartis Investigative Site	Atlanta	Georgia
United States	Novartis Investigative Site	Augusta	Georgia
United States	Novartis Investigative Site	Augusta	Georgia
United States	Novartis Investigative Site	Austin	Texas
United States	Novartis Investigative Site	Aventura	Florida
United States	Novartis Investigative Site	Baltimore	Maryland
United States	Novartis Investigative Site	Belzoni	Mississippi
United States	Novartis Investigative Site	Bennington	Vermont
United States	Novartis Investigative Site	Birmingham	Alabama
United States	Novartis Investigative Site	Birmingham	Alabama
United States	Novartis Investigative Site	Boca Raton	Florida
United States	Novartis Investigative Site	Bridgeport	Connecticut
United States	Novartis Investigative Site	Burke	Virginia
United States	Novartis Investigative Site	Burlingame	California
United States	Novartis Investigative Site	Burlington	Massachusetts
United States	Novartis Investigative Site	Burlington	Vermont
United States	Novartis Investigative Site	Champaign	Illinois
United States	Novartis Investigative Site	Charleston	South Carolina
United States	Novartis Investigative Site	Charleston	West Virginia
United States	Novartis Investigative Site	Cincinnati	Ohio
United States	Novartis Investigative Site	Cleveland	Ohio
United States	Novartis Investigative Site	Collierville	Tennessee
United States	Novartis Investigative Site	Columbia	South Carolina
United States	Novartis Investigative Site	Cumming	Georgia
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Denver	Colorado
United States	Novartis Investigative Site	Detroit	Michigan
United States	Novartis Investigative Site	Detroit	Michigan
United States	Novartis Investigative Site	Dover	New Hampshire
United States	Novartis Investigative Site	Fayetteville	Arkansas
United States	Novartis Investigative Site	Fremont	Nebraska
United States	Novartis Investigative Site	Ft. Lauderdale	Florida
United States	Novartis Investigative Site	Fullerton	California
United States	Novartis Investigative Site	Greenville	South Carolina
United States	Novartis Investigative Site	Gulfport	Mississippi
United States	Novartis Investigative Site	Haverhill	Massachusetts
United States	Novartis Investigative Site	Hollywood	Florida
United States	Novartis Investigative Site	Honolulu	Hawaii
United States	Novartis Investigative Site	Honolulu	Hawaii
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Huntington Beach	California
United States	Novartis Investigative Site	Huntsville	Alabama
United States	Novartis Investigative Site	Irving	Texas
United States	Novartis Investigative Site	Jackson	Mississippi
United States	Novartis Investigative Site	Jacksonville	Florida
United States	Novartis Investigative Site	Jacksonville	Florida
United States	Novartis Investigative Site	Jacksonville	Florida
United States	Novartis Investigative Site	Jacksonville	Florida
United States	Novartis Investigative Site	Jamaica Plain	Massachusetts
United States	Novartis Investigative Site	Kalamazoo	Michigan
United States	Novartis Investigative Site	Lake Zurich	Illinois
United States	Novartis Investigative Site	Lancaster	Pennsylvania
United States	Novartis Investigative Site	Lansdale	Pennsylvania
United States	Novartis Investigative Site	Lauderdale Lakes	Florida
United States	Novartis Investigative Site	Livonia	Michigan
United States	Novartis Investigative Site	Louisville	Kentucky
United States	Novartis Investigative Site	Lyndhurst	Ohio
United States	Novartis Investigative Site	McAllen	Texas
United States	Novartis Investigative Site	Melrose Park	Pennsylvania
United States	Novartis Investigative Site	Metairie	Louisiana
United States	Novartis Investigative Site	Minneapolis	Minnesota
United States	Novartis Investigative Site	Minneapolis	Minnesota
United States	Novartis Investigative Site	Mobile	Alabama
United States	Novartis Investigative Site	Mobile	Alabama
United States	Novartis Investigative Site	Montgomery	Alabama
United States	Novartis Investigative Site	Muscle Shoals	Alabama
United States	Novartis Investigative Site	Natick	Massachusetts
United States	Novartis Investigative Site	Norman	Oklahoma
United States	Novartis Investigative Site	North Dartmouth	Massachusetts
United States	Novartis Investigative Site	North Richland Hills	Texas
United States	Novartis Investigative Site	Oakland	California
United States	Novartis Investigative Site	Oklahoma City	Oklahoma
United States	Novartis Investigative Site	Omaha	Nebraska
United States	Novartis Investigative Site	Orangeburg	South Carolina
United States	Novartis Investigative Site	Pasadena	California
United States	Novartis Investigative Site	Pensacola	Florida
United States	Novartis Investigative Site	Peoria	Illinois
United States	Novartis Investigative Site	Peoria	Arizona
United States	Novartis Investigative Site	Philadelphia	Pennsylvania
United States	Novartis Investigative Site	Phoenix	Arizona
United States	Novartis Investigative Site	Plano	Texas
United States	Novartis Investigative Site	Plantation	Florida
United States	Novartis Investigative Site	Princeton Junction	New Jersey
United States	Novartis Investigative Site	Renton	Washington
United States	Novartis Investigative Site	Riverside	California
United States	Novartis Investigative Site	Rochester	New York
United States	Novartis Investigative Site	San Antonio	Texas
United States	Novartis Investigative Site	San Antonio	Texas
United States	Novartis Investigative Site	San Antonio	Texas
United States	Novartis Investigative Site	Slidell	Louisiana
United States	Novartis Investigative Site	Spring Valley	California
United States	Novartis Investigative Site	Springfield	Missouri
United States	Novartis Investigative Site	St. Louis	Missouri
United States	Novartis Investigative Site	St. Louis	Missouri
United States	Novartis Investigative Site	St. Louis Park	Minnesota
United States	Novartis Investigative Site	Temple	Texas
United States	Novartis Investigative Site	Topeka	Kansas
United States	Novartis Investigative Site	Torrance	California
United States	Novartis Investigative Site	Tucson	Arizona
United States	Novartis Investigative Site	Tucson	Arizona
United States	Novartis Investigative Site	Tulsa	Oklahoma
United States	Novartis Investigative Site	Walnut Creek	California
United States	Novartis Investigative Site	Waltham	Massachusetts
United States	Novartis Investigative Site	Warwick	Rhode Island
United States	Novartis Investigative Site	West Palm Beach	Florida
United States	Novartis Investigative Site	Worcester	Massachusetts
United States	Novartis Investigative Site	Wyomissing	Pennsylvania
Venezuela	Novartis Investigative Site	Caracas	Distrito Capital
Venezuela	Novartis Investigative Site	Caracas	Distrito Capital
Venezuela	Novartis Investigative Site	Caracas	Distrito Capital
Venezuela	Novartis Investigative Site	Caracas	Distrito Capital
Venezuela	Novartis Investigative Site	Caracas	Distrito Capital
Venezuela	Novartis Investigative Site	Caracas	Estado Miranda
Venezuela	Novartis Investigative Site	Puerto Ordaz	Estado Bolívar
Venezuela	Novartis Investigative Site	Valencia	Estado Carabobo

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Venezuela,  Argentina,  Austria,  Belgium,  Brazil,  Canada,  China,  Colombia,  Czech Republic,  Denmark,  Finland,  France,  Germany,  Greece,  Guatemala,  Hungary,  India,  Italy,  Japan,  Korea, Republic of,  Lithuania,  Netherlands,  Norway,  Peru,  Portugal,  Puerto Rico,  Singapore,  Slovakia,  South Africa,  Spain,  Sweden,  Switzerland,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percentage of Participants With Angioedema/Angioedema-like or Colorectal Events (Core : Active Treatment Phase)	AEs of special interest were reported according to a post-marketing commitment to Health Authorities and included angioedema/angioedema-like events and colorectal events/ procedures	Time from randomization to the first event (Maximum 50 months)	Yes
Other	Change From Baseline in Urinary Albumin to Creatinine Ratio (UACR) to Month 6 and to Last Measurement (Core : Active Treatment Phase)	Baseline is the geometric mean of last 3 measurements before visit 3, Post-baseline value is the geometric mean of last 3 measurements during each visit.; Change from Baseline = Post - Baseline.	Baseline, Month 6 , last measurement (maximum at 50 months)	No
Other	Mean Changes in Estimated Glomerular Filtration Rate (eGFR) From Baseline to Month 3 and Month 6 (Core : Active Treatment Phase)	The eGFR calculation was based on the Abbreviated Modification of Diet in Renal Disease (MDRD) Study Equation. Using this method, the applicable MDRD formula to calculate eGFR was as follows: Estimated GFR (mL/min/1.73 m^2) = 175 x (serum creatinine in mg/dL) -1.154 x (Age in years) -0.203 x (0.742 if female) x (1.210 if Black); Mean changes in eGFR from baseline to month 3 and month 6 were included for analysis. The LS Mean and Standard Error were based on an ANCOVA repeated-measure model with treatment, visit, treatment-by-visit and baseline eGFR as effect terms.	Baseline to Month 3 and Month 6	No
Other	Percentage of Participants With Angioedema/Angioedema-like Events or Colorectal Events (Extension Phase)	AEs of special interest were reported according to a post-marketing commitment to Health Authorities and included angioedema/angioedema-like events and colorectal events/ procedures.	From cut-off date (20Dec2011/End of Treatment (EOT) ) to the first event after cut-off date (9 months in average)	Yes
Primary	Percentage of Participants With Occurrence of Primary Composite Endpoint (Core : Active Treatment Phase)	Occurrence was defined as the first event of the following composite primary endpoint: Cardiovascular (CV) death; Resuscitated sudden death; Non-fatal myocardial infarction (MI); Non-fatal stroke; Unplanned hospitalization for heart failure (HF); Onset of end-stage renal disease (ESRD) or death due to renal failure. Onset of ESRD was defined as initiation of dialysis, renal transplantation, or a serum creatinine concentration above 6.0 mg/dL (530 µmol/L), sustained for at least a month.; Doubling of baseline serum creatinine concentration, sustained for at least one month. To fulfill the endpoint, the serum creatinine concentration had to be above the upper limit of normal for men and women according to the central laboratory. The upper limit of normal for men is 1.20 mg/dL and for women is 0.91 mg/dL.	Time from randomization to the first event (Maximum 50 months)	No
Primary	Percentage of Participants With Cardiovascular (CV) Death (Core: Active Treatment Phase)		Time from randomization to the first event (Maximum 50 months)	No
Primary	Percentage of Participants With Resuscitated Sudden Death (Core: Active Treatment Phase)	Resuscitated sudden death was adjudicated when a subject experiences sudden death or cardiac arrest and is successfully resuscitated by cardioversion, defibrillation or cardiopulmonary resuscitation with a meaningful recovery of consciousness. This definition excludes known transient losses of consciousness such as seizure or vasovagal episodes that do not reflect significant cardiac dysfunction.	Time from randomization to the first event (Maximum 50 Months)	No
Primary	Percentage of Participants With Fatal/Non-fatal Myocardial Infarction (MI) (Core: Active Treatment Phase)		Time from randomization to the first event (Maximum 50 Months)	No
Primary	Percentage of Participants With Fatal/Non-fatal Stroke (Core: Active Treatment Phase)		Time from randomization to the first event (Maximum 50 Months)	No
Primary	Percentage of Participants With Onset of End-stage Renal Disease (ESRD) (Core: Active Treatment Phase)	ESRD is defined as initiation of dialysis, renal transplantation, or a serum creatinine concentration above 6.0 mg/dL (530 µmol per liter) or renal death	Time from randomization to the first event (Maximum 50 Months)	No
Primary	Percentage of Participants With Doubling of Baseline Serum Creatinine Concentration, Sustained for at Least One Month (Core: Active Treatment Phase)	To fulfill the endpoint, the serum creatinine concentration had to be above the upper limit of normal for men and women according to the central laboratory. The upper limit of normal for men is 1.20 mg/dL and for women is 0.91 mg/dL.	Time from randomization to the first event (Maximum 50 Months)	No
Primary	Percentage of Participants With Unplanned Hospitalization for Heart Failure (Core: Active Treatment Phase)		Time from randomization to the first event (Maximum 50 Months)	No
Primary	Percentage of Participants With All Cause Mortality (Core: Active Treatment Phase)		Time from randomization to the first event (Maximum 50 months)	No
Primary	Percentage of Participants With Occurrence of Primary Composite Endpoint (Extension Phase)	Occurrence was defined as the first event of the following composite primary endpoint: Cardiovascular (CV) death; Resuscitated sudden death; Non-fatal myocardial infarction (MI); Non-fatal stroke; Unplanned hospitalization for heart failure (HF); Onset of end-stage renal disease (ESRD) or death due to renal failure. Onset of ESRD was defined as initiation of dialysis, renal transplantation, or a serum creatinine concentration above 6.0 mg/dL (530 µmol/L), sustained for at least a month.; Doubling of baseline serum creatinine concentration, sustained for at least one month. To fulfill the endpoint, the serum creatinine concentration had to be above the upper limit of normal for men and women according to the central laboratory. The upper limit of normal for men is 1.20 mg/dL and for women is 0.91 mg/dL.	From cut-off date (20Dec2011/End of Treatment (EOT) ) to the first event after cut-off date (9 months in average)	No
Primary	Percentage of Participants With Cardiovascular (CV) Death (Extension Phase)		from cut-off date (20Dec2011/End of Treatment (EOT) ) to the first event after cut-off date (9 months in average)	No
Primary	Percentage of Participants With Resuscitated Sudden Death (Extension Phase)		From cut-off date (20Dec2011/End of Treatment (EOT) ) to the first event after cut-off date (9 months in average)	No
Primary	Percentage of Participants Fatal/Non-fatal Myocardial Infarction (MI) (Extension Phase)		From cut-off date (20Dec2011/End of Treatment (EOT) ) to the first event after cut-off date (9 month in average)	No
Primary	Percentage of Participants With Fatal/Non-fatal Stroke (Extension Phase)		From cut-off date (20Dec2011/End of Treatment (EOT) ) to the first event after cut-off date (9 months in average)	No
Primary	Percentage of Participants With Onset of End-stage Renal Disease (ESRD) (Extension Phase)	ESRD is defined as initiation of dialysis, renal transplantation, or a serum creatinine concentration above 6.0 mg/dL (530 µmol per liter) or renal death	From cut-off date (20Dec2011/End of Treatment (EOT) ) to the first event after cut-off date (9 months in average)	No
Primary	Percentage of Participants Doubling of Baseline Serum Creatinine Concentration, Sustained for at Least One Month (Extension Phase)	To fulfill the endpoint, the serum creatinine concentration had to be above the upper limit of normal for men and women according to the central laboratory. The upper limit of normal for men is 1.20 mg/dL and for women is 0.91 mg/dL.	From cut-off date (20Dec2011/End of Treatment (EOT) ) to the first event after cut-off date (9 months in average)	No
Primary	Percentage of Participants With Unplanned Hospitalization for Heart Failure (Extension Phase)		From cut-off date (20Dec2011/End of Treatment (EOT) ) to the first event after cut-off date (9 months in average)	No
Primary	Percentage of Participants With All Cause Mortality (Extension Phase)		from cut-off date (20Dec2011/End of Treatment (EOT) ) to the first event after cut-off date (9 months in average)	No
Secondary	Percentage of Participants With Occurrence of Secondary Cardiovascular Composite Endpoint (Core: Active Treatment Phase)	Occurrence was defined as the first event of the following secondary cardiovascular composite endpoint: Cardiovascular (CV) death; Resuscitated sudden death; Non-fatal myocardial infarction (MI); Non-fatal stroke; Unplanned hospitalization for heart failure (HF)	Time from randomization to the first event (Maximum 50 months)	No
Secondary	Percentage of Participants With Occurrence of Secondary Renal Composite Endpoint (Core: Active Treatment Phase)	Occurrence was defined as the first event of the following secondary renal composite endpoint: Onset of end-stage renal disease (ESRD) or death due to renal failure. Onset of ESRD was defined as initiation of dialysis, renal transplantation, or a serum creatinine concentration above 6.0 mg/dL (530 µmol/L), sustained for at least a month.; Doubling of baseline serum creatinine concentration, sustained for at least one month. To fulfill the endpoint, the serum creatinine concentration had to be above the upper limit of normal for men and women according to the central laboratory.The upper limit of normal for men is 1.20 mg/dL and for women is 0.91 mg/dL.	Time from randomization to the first event (Maximum 50 months)	No
Secondary	Percentage of Participants With Occurrence of Secondary Cardiovascular Composite Endpoint (Extension Phase)	Occurrence was defined as the first event of the following secondary cardiovascular composite endpoint: Cardiovascular (CV) death; Resuscitated sudden death; Non-fatal myocardial infarction (MI); Non-fatal stroke; Unplanned hospitalization for heart failure (HF)	From cut-off date (20Dec2011/End of Treatment (EOT) ) to the first event after cut-off date (9 months in average)	No
Secondary	Percentage of Participants With Occurrence of Secondary Renal Composite Endpoint (Extension Phase)	Occurrence was defined as the first event of the following secondary renal composite endpoint: Onset of end-stage renal disease (ESRD) or death due to renal failure. Onset of ESRD was defined as initiation of dialysis, renal transplantation, or a serum creatinine concentration above 6.0 mg/dL (530 µmol/L), sustained for at least a month.; Doubling of baseline serum creatinine concentration, sustained for at least one month. To fulfill the endpoint, the serum creatinine concentration had to be above the upper limit of normal for men and women according to the central laboratory. The upper limit of normal for men is 1.20 mg/dL and for women is 0.91 mg/dL.	From cut-off date (20Dec2011/End of Treatment (EOT) ) to the first event after cut-off date (9 months in average)	No