A Study of the Effects of Canagliflozin (JNJ-28431754) on Renal Endpoints in Adult Participants With Type 2 Diabetes Mellitus

NCT ID: NCT01989754

Last Updated: 2018-12-11

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

5813 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-01-16

Study Completion Date

2017-02-23

Brief Summary

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The purpose of this study is to assess the effect of canagliflozin compared to placebo on progression of albuminuria in participants with Type 2 Diabetes Mellitus receiving standard care but with inadequate glycemic control and at elevated risk of cardiovascular events.

Detailed Description

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The study will be conducted in adult participants with Type 2 Diabetes Mellitus (T2DM), receiving standard of care for hyperglycemia and cardiovascular (CV) risk factors, who have either a history of a prior CV event or 2 or more risk factors for a CV event. Participants will be randomly assigned in a 1:1 ratio to canagliflozin or matching placebo to be taken once daily. Canagliflozin will be provided at a dose of 100 mg/day through Week 13 and then increased at the discretion of the investigator to a dose of 300 mg/day, if the participant requires additional glycemic control and is tolerating the 100 mg dose.

The study consists of a 2-week screening period and a double-blind treatment period lasting between 78 and 156 weeks; study completion is targeted for when the last subject randomized has approximately 78 weeks of follow-up or when 688 major adverse cardiovascular events are accumulated between CANVAS and CANVAS-R. A total of 5,700 participants are targeted to be recruited into the study. Participants can be either drug naïve to antihyperglycemic agents, using monotherapy, or using combination of antihyperglycemic therapy for the control of blood glucose levels.

The completion target was reached in February 2017.

Conditions

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Diabetes Mellitus, Type 2 Albuminuria

Keywords

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Albuminuria Canagliflozin Cardiovascular outcomes Type 2 Diabetes Mellitus T2DM JNJ-28431754 Antihyperglycemic Agent

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Canagliflozin (JNJ-28431754)

Each patient will receive canagliflozin (JNJ-28431754) 100 mg once daily during the first 13 weeks, then the dose may be increased to 300 mg once daily.

Group Type EXPERIMENTAL

Canagliflozin, 100 mg

Intervention Type DRUG

One 100 mg capsule taken orally (by mouth) once daily

Canagliflozin, 300 mg

Intervention Type DRUG

One 300 mg capsule taken orally (by mouth) once daily

Placebo

Each patient will receive placebo (inactive medication) once daily.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

One placebo capsule taken orally (by mouth) once daily for 156 weeks

Interventions

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Placebo

One placebo capsule taken orally (by mouth) once daily for 156 weeks

Intervention Type DRUG

Canagliflozin, 100 mg

One 100 mg capsule taken orally (by mouth) once daily

Intervention Type DRUG

Canagliflozin, 300 mg

One 300 mg capsule taken orally (by mouth) once daily

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Must have a diagnosis of type 2 diabetes mellitus
* Must have inadequate diabetes control (as defined by glycosylated hemoglobin level \>=7.0% to \<=10.5% at screening)
* Greater than or equal to (\>=) 30 yrs old with history of cardiovascular (CV) event, or \>= 50 yrs old with high risk of CV events
* Must be either not on antihyperglycemic agents (AHA) therapy, or on AHA monotherapy, or combination AHA therapy with any approved agent for the control of blood glucose levels.

Exclusion Criteria

* History of diabetic ketoacidosis, type 1 diabetes mellitus, pancreas or beta-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy
* History of one or more severe hypoglycemic episode within 6 months before screening
* History of hereditary glucose-galactose malabsorption or primary renal glucosuria
* Ongoing, inadequately controlled thyroid disorder
* Renal disease that required treatment with immunosuppressive therapy or a history of chronic dialysis or renal transplant
* Myocardial infarction, unstable angina, revascularization procedure, or cerebrovascular accident within 3 months before screening.
Minimum Eligible Age

30 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The George Institute for Global Health, Australia

OTHER

Sponsor Role collaborator

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

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Little Rock, Arkansas, United States

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Carmichael, California, United States

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Concord, California, United States

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Pismo Beach, California, United States

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Roseville, California, United States

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Thousand Oaks, California, United States

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Denver, Colorado, United States

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Hollywood, Florida, United States

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Jacksonville, Florida, United States

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Miami, Florida, United States

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New Port Richey, Florida, United States

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Opa-locka, Florida, United States

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Orlando, Florida, United States

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Palm Harbor, Florida, United States

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Tampa, Florida, United States

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Meridian, Idaho, United States

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Chicago, Illinois, United States

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Valparaiso, Indiana, United States

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Topeka, Kansas, United States

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Louisville, Kentucky, United States

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Mandeville, Louisiana, United States

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Metairie, Louisiana, United States

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Elkridge, Maryland, United States

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Flint, Michigan, United States

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Picayune, Mississippi, United States

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Kansas City, Missouri, United States

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St Louis, Missouri, United States

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Washington, Missouri, United States

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Omaha, Nebraska, United States

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Las Vegas, Nevada, United States

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Cornelius, North Carolina, United States

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Hickory, North Carolina, United States

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Mooresville, North Carolina, United States

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Canal Fulton, Ohio, United States

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Franklin, Ohio, United States

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Mason, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Beaver, Pennsylvania, United States

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Levittown, Pennsylvania, United States

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Norristown, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Tipton, Pennsylvania, United States

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Greer, South Carolina, United States

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Jefferson City, Tennessee, United States

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Austin, Texas, United States

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Pearland, Texas, United States

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Bountiful, Utah, United States

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Draper, Utah, United States

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Salt Lake City, Utah, United States

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West Jordan, Utah, United States

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South Burlington, Vermont, United States

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Falls Church, Virginia, United States

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Norfolk, Virginia, United States

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Virginia Beach, Virginia, United States

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Spokane, Washington, United States

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Milwaukee, Wisconsin, United States

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Wauwatosa, Wisconsin, United States

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Buenos Aires, , Argentina

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Ciudad de Buenos Aires, , Argentina

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Córdoba, , Argentina

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Mar del Plata, , Argentina

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Morón, , Argentina

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Rosario, , Argentina

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Zarate, Buenos Aires, , Argentina

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Box Hill, , Australia

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Cairns, , Australia

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Daw Park, , Australia

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Freemantle, , Australia

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Liverpool, , Australia

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Melbourne, , Australia

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Newcastle, , Australia

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Sherwood, , Australia

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Sydney, , Australia

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Tasmania, , Australia

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Woden, , Australia

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Woolloongabba, , Australia

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Bonheiden, , Belgium

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Bruges, , Belgium

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Edegem, , Belgium

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Ghent, , Belgium

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La Louvière, , Belgium

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Leuven, , Belgium

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Liège, , Belgium

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Liÿge, , Belgium

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Merksem, , Belgium

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Ransart, , Belgium

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Roeselare, , Belgium

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Tessenderlo, , Belgium

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Belém, , Brazil

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Belo Horizonte, , Brazil

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Campinas, , Brazil

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Caxias do Sul, , Brazil

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Curitiba, , Brazil

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Fortaleza, , Brazil

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Mogi das Cruzes, , Brazil

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Passo Fundo, , Brazil

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Porto Alegre, , Brazil

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Rio de Janeiro, , Brazil

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São José do Rio Preto, , Brazil

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São Paulo, , Brazil

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Coquitlam, British Columbia, Canada

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Winnipeg, Manitoba, Canada

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Halifax, Nova Scotia, Canada

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Guelph, Ontario, Canada

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Mississauga, Ontario, Canada

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Oshawa, Ontario, Canada

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Sarnia, Ontario, Canada

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Thornhill, Ontario, Canada

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Toronto, Ontario, Canada

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Laval, Quebec, Canada

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Lévis, Quebec, Canada

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Québec, Quebec, Canada

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Saint Marc Des Carriéres, Quebec, Canada

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Sherbrooke, Quebec, Canada

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Westmont, Quebec, Canada

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Saskatoon, Saskatchewan, Canada

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Baotou, , China

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Beijing, , China

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Hangzhou, , China

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Jinan, , China

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Shenyang, , China

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Wuxi, , China

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Beroun, , Czechia

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Ostrava, , Czechia

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Pilsen, , Czechia

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Prague, , Czechia

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Znojmo, , Czechia

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Amiens, , France

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Bois-Guillaume, , France

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Bordeaux, , France

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Dijon, , France

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Grenoble, , France

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La Rochelle, , France

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Le Creusot, , France

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Narbonne, , France

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Paris, , France

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Poitiers, , France

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Aschaffenburg, , Germany

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Aßlar, , Germany

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Bad Oeynhausen, , Germany

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Dortmund, , Germany

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Dresden, , Germany

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Freiburg im Breisgau, , Germany

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Hanover, , Germany

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Kassel, , Germany

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Mainz, , Germany

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Neuwied, , Germany

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Saarbrücken, , Germany

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Villingen-Schwenningen, , Germany

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Balatonfüred, , Hungary

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Budapest, , Hungary

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Dunaújváros, , Hungary

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Eger, , Hungary

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Kecskemét, , Hungary

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Nagykanizsa, , Hungary

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Pécs, , Hungary

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Székesfehérvár, , Hungary

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Szikszó, , Hungary

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Szombathely, , Hungary

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Zalaegerszeg, , Hungary

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*Osenza*, , Italy

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Arenzano, , Italy

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Bologna, , Italy

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Catanzaro, , Italy

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Chieri (Torino), , Italy

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Florence, , Italy

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Messina, , Italy

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Milan, , Italy

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Napoli, , Italy

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Ravenna, , Italy

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Roma, , Italy

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Sesto San Giovanni (Milano), , Italy

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Verona, , Italy

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Batu Caves, , Malaysia

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George Town, , Malaysia

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Ipoh, , Malaysia

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Kelantan, , Malaysia

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Kota Bharu, , Malaysia

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Kuala Lumpur, , Malaysia

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Kuching, , Malaysia

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Aguascalientes, , Mexico

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Celaya, , Mexico

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Cuernavaca, , Mexico

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Culiacán, , Mexico

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Guadalajara, , Mexico

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México, , Mexico

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Pachuca, , Mexico

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Querétaro, , Mexico

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San Luis Potosí City, , Mexico

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Tampico, , Mexico

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Almelo, , Netherlands

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Almere Stad, , Netherlands

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Amersfoort, , Netherlands

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Amsterdam, , Netherlands

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Dordrecht, , Netherlands

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Eindhoven, , Netherlands

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Groningen, , Netherlands

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Hardenberg, , Netherlands

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Hoogeveen, , Netherlands

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Hoogezand, , Netherlands

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Kloosterhaar, , Netherlands

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Leiden, , Netherlands

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Meppel, , Netherlands

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Poortvliet, , Netherlands

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Rotterdam, , Netherlands

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Utrecht, , Netherlands

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Velp, , Netherlands

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Waalwijk, , Netherlands

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Wamel, , Netherlands

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Zoetermeer, , Netherlands

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Zwijndrecht, , Netherlands

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Auckland, , New Zealand

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Christchurch, , New Zealand

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Newtown, , New Zealand

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Palmerston North, , New Zealand

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Rotorua, , New Zealand

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Tauranga, , New Zealand

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Wellington, , New Zealand

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Bialystok, , Poland

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Bydgoszcz, , Poland

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Chrzanów, , Poland

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Gdansk, , Poland

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Grodzisk Mazowiecki, , Poland

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Katowice, , Poland

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Krakow, , Poland

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Lublin, , Poland

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Oświęcim, , Poland

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Torun, , Poland

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Tychy, , Poland

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Warsaw, , Poland

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Wroclaw, , Poland

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Ponce Pr, , Puerto Rico

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Trujillo Alto, , Puerto Rico

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Arkhangelsk, , Russia

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Barnaul, , Russia

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Chelyabinsk, , Russia

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Kemerovo, , Russia

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Nizhny Novgorod, , Russia

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Penza, , Russia

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Rostov-on-Don, , Russia

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Saint Petersburg, , Russia

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Samara, , Russia

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Saratov, , Russia

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Smolensk, , Russia

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Syktyvkar, , Russia

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Tyumen, , Russia

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Vsevolzhsk, , Russia

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Yaroslavl, , Russia

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Ansan, , South Korea

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Bucheon-si, , South Korea

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Busan, , South Korea

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Changwon, , South Korea

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Cheongju-si, , South Korea

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Daegu, , South Korea

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Gyeonggi-do, , South Korea

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Iksan, , South Korea

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Incheon, , South Korea

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Jeonju, , South Korea

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Seongnam-si, , South Korea

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Seoul, , South Korea

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Suwon, , South Korea

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Ulsan, , South Korea

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Wŏnju, , South Korea

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A Coruña, , Spain

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Alcalá de Henares, , Spain

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Alicante, , Spain

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Almería, , Spain

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Alzira, , Spain

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Barcelona, , Spain

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Ciudad Real, , Spain

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Córdoba, , Spain

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Ferrol, , Spain

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Figueres, , Spain

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Galdakao, , Spain

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Madrid, , Spain

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Málaga, , Spain

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Móstoles, , Spain

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Palma de Mallorca, , Spain

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Sabadell, , Spain

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San Sebastián de los Reyes, , Spain

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Sant Joan d'Alacant, , Spain

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Santa Cruz de Tenerife, , Spain

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Santiago de Compostela, , Spain

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Segovia, , Spain

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Seville, , Spain

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Valencia, , Spain

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Viladecans, , Spain

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Borås, , Sweden

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Gothenburg, , Sweden

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Helsingborg, , Sweden

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Karlstad, , Sweden

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Linköping, , Sweden

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Lund, , Sweden

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Malmo, , Sweden

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Stockholm, , Sweden

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Uddevalla, , Sweden

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Uppsala, , Sweden

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Vällingby, , Sweden

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Västra Frölunda, , Sweden

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Kaohsiung County, , Taiwan

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Taichung, , Taiwan

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Tainan City, , Taiwan

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Taipei, , Taiwan

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Tiachung, , Taiwan

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Xindian, , Taiwan

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Cherkasy, , Ukraine

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Chernivtsy, , Ukraine

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Dnipropetrovsk, , Ukraine

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Ivan-Frankivsk, , Ukraine

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Ivano-Frankivsk, , Ukraine

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Kharkiv, , Ukraine

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Kiev, , Ukraine

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Kyiv, , Ukraine

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Lviv, , Ukraine

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Odesa, , Ukraine

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Poltava, , Ukraine

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Sumy, , Ukraine

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Ternopil, , Ukraine

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Uzhhorod, , Ukraine

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Vinnitsa, , Ukraine

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Vinnytsia, , Ukraine

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Zaporizhzhia, , Ukraine

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Zaporizhzhya, , Ukraine

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Addlestone, , United Kingdom

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Belfast, , United Kingdom

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Birmingham, , United Kingdom

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Blackburn, , United Kingdom

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Bristol, , United Kingdom

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Bury St Edmunds, , United Kingdom

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Chesterfield, , United Kingdom

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Derby, , United Kingdom

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Doncaster, , United Kingdom

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Ipswich, , United Kingdom

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Leicester, , United Kingdom

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Liverpool, , United Kingdom

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Manchester, , United Kingdom

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Salford, , United Kingdom

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Taunton, , United Kingdom

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Torquay, , United Kingdom

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Truro, , United Kingdom

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Wellingborough, , United Kingdom

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Welwyn Garden City, , United Kingdom

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Countries

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United States Argentina Australia Belgium Brazil Canada China Czechia France Germany Hungary Italy Malaysia Mexico Netherlands New Zealand Poland Puerto Rico Russia South Korea Spain Sweden Taiwan Ukraine United Kingdom

References

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Doi Y, Hamano T, Yamaguchi O, Isaka Y. Canagliflozin may increase thromboembolic events in males with erythrocytosis but not in females. Blood Adv. 2025 Jul 8;9(13):3202-3212. doi: 10.1182/bloodadvances.2025016320.

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Borisov AN, Kutz A, Christ ER, Heim MH, Ebrahimi F. Canagliflozin and Metabolic Associated Fatty Liver Disease in Patients With Diabetes Mellitus: New Insights From CANVAS. J Clin Endocrinol Metab. 2023 Oct 18;108(11):2940-2949. doi: 10.1210/clinem/dgad249.

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Ferrannini G, Pollock C, Natali A, Yavin Y, Mahaffey KW, Ferrannini E. Extremes of both weight gain and weight loss are associated with increased incidence of heart failure and cardiovascular death: evidence from the CANVAS Program and CREDENCE. Cardiovasc Diabetol. 2023 Apr 29;22(1):100. doi: 10.1186/s12933-023-01832-5.

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Nunes JC, Yu J, Arnott C, Jardine MJ, Perkovic V, Mahaffey KW. Canagliflozin, mental health adverse events and diabetes: Exploratory analysis of the CREDENCE trial and CANVAS Program. Diabetes Obes Metab. 2022 Dec;24(12):2459-2464. doi: 10.1111/dom.14832. Epub 2022 Aug 19. No abstract available.

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Reference Type DERIVED
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Neuen BL, Ohkuma T, Neal B, Matthews DR, de Zeeuw D, Mahaffey KW, Fulcher G, Blais J, Li Q, Jardine MJ, Perkovic V, Wheeler DC. Relative and Absolute Risk Reductions in Cardiovascular and Kidney Outcomes With Canagliflozin Across KDIGO Risk Categories: Findings From the CANVAS Program. Am J Kidney Dis. 2021 Jan;77(1):23-34.e1. doi: 10.1053/j.ajkd.2020.06.018. Epub 2020 Sep 21.

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Oshima M, Neal B, Toyama T, Ohkuma T, Li Q, de Zeeuw D, Heerspink HJL, Mahaffey KW, Fulcher G, Canovatchel W, Matthews DR, Perkovic V. Different eGFR Decline Thresholds and Renal Effects of Canagliflozin: Data from the CANVAS Program. J Am Soc Nephrol. 2020 Oct;31(10):2446-2456. doi: 10.1681/ASN.2019121312. Epub 2020 Jul 21.

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Matthews DR, Wysham C, Davies M, Slee A, Alba M, Lee M, Perkovic V, Mahaffey KW, Neal B. Effects of canagliflozin on initiation of insulin and other antihyperglycaemic agents in the CANVAS Program. Diabetes Obes Metab. 2020 Nov;22(11):2199-2203. doi: 10.1111/dom.14143. Epub 2020 Aug 24.

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PMID: 32691499 (View on PubMed)

Li J, Woodward M, Perkovic V, Figtree GA, Heerspink HJL, Mahaffey KW, de Zeeuw D, Vercruysse F, Shaw W, Matthews DR, Neal B. Mediators of the Effects of Canagliflozin on Heart Failure in Patients With Type 2 Diabetes. JACC Heart Fail. 2020 Jan;8(1):57-66. doi: 10.1016/j.jchf.2019.08.004. Epub 2019 Oct 29.

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Zhou Z, Jardine M, Perkovic V, Matthews DR, Mahaffey KW, de Zeeuw D, Fulcher G, Desai M, Oh R, Simpson R, Watts NB, Neal B. Canagliflozin and fracture risk in individuals with type 2 diabetes: results from the CANVAS Program. Diabetologia. 2019 Oct;62(10):1854-1867. doi: 10.1007/s00125-019-4955-5. Epub 2019 Aug 10.

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Figtree GA, Radholm K, Barrett TD, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Matthews DR, Shaw W, Neal B. Effects of Canagliflozin on Heart Failure Outcomes Associated With Preserved and Reduced Ejection Fraction in Type 2 Diabetes Mellitus. Circulation. 2019 May 28;139(22):2591-2593. doi: 10.1161/CIRCULATIONAHA.119.040057. Epub 2019 Mar 17. No abstract available.

Reference Type DERIVED
PMID: 30882240 (View on PubMed)

Zhou Z, Lindley RI, Radholm K, Jenkins B, Watson J, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Shaw W, Oh R, Desai M, Matthews DR, Neal B. Canagliflozin and Stroke in Type 2 Diabetes Mellitus. Stroke. 2019 Feb;50(2):396-404. doi: 10.1161/STROKEAHA.118.023009.

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Neuen BL, Ohkuma T, Neal B, Matthews DR, de Zeeuw D, Mahaffey KW, Fulcher G, Desai M, Li Q, Deng H, Rosenthal N, Jardine MJ, Bakris G, Perkovic V. Cardiovascular and Renal Outcomes With Canagliflozin According to Baseline Kidney Function. Circulation. 2018 Oct 9;138(15):1537-1550. doi: 10.1161/CIRCULATIONAHA.118.035901.

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Perkovic V, de Zeeuw D, Mahaffey KW, Fulcher G, Erondu N, Shaw W, Barrett TD, Weidner-Wells M, Deng H, Matthews DR, Neal B. Canagliflozin and renal outcomes in type 2 diabetes: results from the CANVAS Program randomised clinical trials. Lancet Diabetes Endocrinol. 2018 Sep;6(9):691-704. doi: 10.1016/S2213-8587(18)30141-4. Epub 2018 Jun 21.

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Wittbrodt ET, Eudicone JM, Bell KF, Enhoffer DM, Latham K, Green JB. Eligibility varies among the 4 sodium-glucose cotransporter-2 inhibitor cardiovascular outcomes trials: implications for the general type 2 diabetes US population. Am J Manag Care. 2018 Apr;24(8 Suppl):S138-S145.

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Radholm K, Figtree G, Perkovic V, Solomon SD, Mahaffey KW, de Zeeuw D, Fulcher G, Barrett TD, Shaw W, Desai M, Matthews DR, Neal B. Canagliflozin and Heart Failure in Type 2 Diabetes Mellitus: Results From the CANVAS Program. Circulation. 2018 Jul 31;138(5):458-468. doi: 10.1161/CIRCULATIONAHA.118.034222.

Reference Type DERIVED
PMID: 29526832 (View on PubMed)

Mahaffey KW, Neal B, Perkovic V, de Zeeuw D, Fulcher G, Erondu N, Shaw W, Fabbrini E, Sun T, Li Q, Desai M, Matthews DR; CANVAS Program Collaborative Group. Canagliflozin for Primary and Secondary Prevention of Cardiovascular Events: Results From the CANVAS Program (Canagliflozin Cardiovascular Assessment Study). Circulation. 2018 Jan 23;137(4):323-334. doi: 10.1161/CIRCULATIONAHA.117.032038. Epub 2017 Nov 13.

Reference Type DERIVED
PMID: 29133604 (View on PubMed)

Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, Shaw W, Law G, Desai M, Matthews DR; CANVAS Program Collaborative Group. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017 Aug 17;377(7):644-657. doi: 10.1056/NEJMoa1611925. Epub 2017 Jun 12.

Reference Type DERIVED
PMID: 28605608 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2013-003050-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

28431754DIA4003

Identifier Type: OTHER

Identifier Source: secondary_id

CR102647

Identifier Type: -

Identifier Source: org_study_id