CANVAS - CANagliflozin cardioVascular Assessment Study (CANVAS)

November 5, 2018 updated by: Janssen Research & Development, LLC

A Randomized, Multicenter, Double-Blind, Parallel, Placebo-Controlled Study of the Effects of JNJ-28431754 on Cardiovascular Outcomes in Adult Subjects With Type 2 Diabetes Mellitus

The study will assess canagliflozin (JNJ-28431754) in the treatment of patients with type 2 diabetes mellitus (T2DM) with regard to cardiovascular (CV) risk for major adverse cardiac events (MACE). Other objectives include evaluating the overall safety, tolerability, and effectiveness of canagliflozin.

The data from this study will be combined with the data from CANVAS-R study (Study of the Effects of Canagliflozin on Renal Endpoints in Adult Subjects with T2DM, NCT01989754) in a pre-specified integrated analysis of CV safety outcomes to satisfy US FDA post-marketing requirements for canagliflozin.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The study will evaluate canagliflozin compared to placebo on CV events including CV death, heart attack, and stroke in patients with T2DM, whose diabetes is not well controlled at the beginning of the study and who have a history of CV events or have a high risk for CV events. The study includes 3 substudies which will compare the effectiveness of lowering blood glucose and assess the safety of canagliflozin relative to placebo in patients receiving specific commonly-used diabetes agents. 4,330 participants will be randomly assigned to treatment with 1 of 2 doses of canagliflozin (100 or 300 mg) or placebo, in a 1:1:1 ratio. This study was originally designed to last for up to 9 years. As per FDA post-marketing requirements for canagliflozin, the study's last subject last visit will now occur when enough MACE events (ie, CV death, nonfatal myocardial infarction, nonfatal stroke) are accumulated between the CANVAS (this study) and CANVAS-R studies. The completion target was reached in February 2017.

Study Type

Interventional

Enrollment (Actual)

4330

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina
      • Capital Federal, Argentina
      • Ciudad Autonma Buenos Aires, Argentina
      • Ciudad Autonoma De Buenos Aires, Argentina
      • Cordoba, Argentina
      • Corrientes, Argentina
      • Godoy Cruz, Argentina
      • Mar Del Plata, Argentina
      • Rosario, Argentina
      • Santa Fe, Argentina
  • Australia
      • Auchenflower, Australia
      • Box Hill, Australia
      • Caboolture, Australia
      • Caringbah, Australia
      • Clayton, Australia
      • Daw Park, Australia
      • East Ringwood, Australia
      • Elizabeth Vale, Australia
      • Hornsby, Nsw 2077, Australia
      • Kippa Ring, Australia
      • Launceston, Australia
      • Liverpool, Australia
      • Melbourne, Australia
      • Milton, Australia
      • Parkville, Australia
      • Reservoir, Australia
      • Sherwood, Australia
      • Southport, Australia
      • St Leonards, Australia
      • West Heidelberg, Australia
      • Wollongong, Australia
      • Woolloongabba, Australia
  • Belgium
      • Arlon, Belgium
      • Bonheiden, Belgium
      • Brussel, Belgium
      • Edegem, Belgium
      • Genk, Belgium
      • Leuven, Belgium
  • Canada
    • Alberta
      • Calgary, Alberta, Canada
    • British Columbia
      • Coquitlam, British Columbia, Canada
    • Manitoba
      • Winnipeg, Manitoba, Canada
    • Newfoundland and Labrador
      • St. John'S, Newfoundland and Labrador, Canada
    • Ontario
      • Brampton, Ontario, Canada
      • London, Ontario, Canada
      • Mississauga, Ontario, Canada
      • Nemarket, Ontario, Canada
      • Sarnia, Ontario, Canada
      • Sudbury, Ontario, Canada
      • Toronto, Ontario, Canada
    • Quebec
      • Laval, Quebec, Canada
      • Lévis, Quebec, Canada
      • Montreal, Quebec, Canada
      • Val-Belair, Quebec, Canada
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada
  • Colombia
      • Bogota, Colombia
      • Floridablanca, Colombia
  • Czechia
      • Kralupy Nad Vltavou, Czechia
      • Moravsky Krumlov, Czechia
      • Olomouc 9, Czechia
      • Ostrava, Czechia
      • Pisek, Czechia
      • Prague 5, Czechia
      • Praha, Czechia
      • Praha 11, Czechia
      • Praha 8, Czechia
      • Znojmo N/A, Czechia
  • Estonia
      • Pärnu, Estonia
      • Tallinn, Estonia
      • Tartu, Estonia
      • Viljandi, Estonia
  • France
      • Amiens, France
      • Nimes Cedex 9, France
      • Pessac, France
  • Germany
      • Berlin, Germany
      • Dortmund, Germany
      • Dresden, Germany
      • Hamburg, Germany
      • Künzing, Germany
      • Mainz, Germany
      • Münster, Germany
      • Pirna, Germany
      • Saarlouis, Germany
      • Speyer, Germany
      • Villingen-Schwenningen, Germany
  • Hungary
      • Budapest, Hungary
      • Kecskemet, Hungary
      • Mosonmagyaróvár, Hungary
      • Zalaegerszeg, Hungary
  • India
      • Ahemadabad, India
      • Ahmedabad, India
      • Ambawadi, India
      • Bangalore, India
      • Bangalore, Karnataka, India
      • Belgaum, India
      • Calicut, India
      • Chennai, India
      • Cochin, India
      • Coimbatore, India
      • Ernakulam, India
      • Ghaziabad, India
      • Hyderabad, India
      • Indore, India
      • Jaipur, India
      • Karnal, India
      • Kerala, India
      • Kochi, India
      • Kolkata, India
      • Lucknow, India
      • Mangalore, India
      • Mumbai, India
      • Mysore, India
      • Nagpur, India
      • New Delhi, India
      • Patna, India
      • Pune, India
      • Rajkot, India
      • Trivandrum, Kerala, India
      • Vadodhara, India
      • Vijayawada, India
      • Visakhapatnam, India
  • Israel
      • Beer Sheba, Israel
      • Holon, Israel
      • Jerusalem, Israel
      • Kfar Saba, Israel
  • Luxembourg
      • Luxembourg, Luxembourg
  • Malaysia
      • Georgetown, Malaysia
      • Johor Bahru, Malaysia
      • Kota Bharu, Malaysia
      • Kuala Lumpur N/A, Malaysia
      • Petaling Jaya, Malaysia
      • Pulau Pinang, Malaysia
      • Subang Jaya, Malaysia
  • Mexico
      • Aguascalientes, Mexico
      • Celaya, Mexico
      • Ciudad De Mexico, Mexico
      • Durango, Mexico
      • Guadalajara, Mexico
      • Monterrey, Mexico
  • Netherlands
      • Almelo, Netherlands
      • Almere, Netherlands
      • Amsterdam, Netherlands
      • Arnhem, Netherlands
      • Delft, Netherlands
      • Den Helder, Netherlands
      • Dordrecht, Netherlands
      • Eindhoven, Netherlands
      • Groningen, Netherlands
      • Hoorn Nh, Netherlands
      • Rotterdam, Netherlands
      • Tilburg, Netherlands
      • Utrecht, Netherlands
      • Velp Gld, Netherlands
      • Zoetermeer, Netherlands
      • Zwijndrecht, Netherlands
  • New Zealand
      • Auckland, New Zealand
      • Christchurch, New Zealand
      • Dunedin, New Zealand
      • Tauranga, New Zealand
      • Wellington, New Zealand
  • Norway
      • Alesund, Norway
      • Asker, Norway
      • Bekkestua, Norway
      • Elverum, Norway
      • Hamar, Norway
      • Lierskogen, Norway
      • Moss, Norway
      • Oslo, Norway
      • Skedsmokorset, Norway
  • Poland
      • Bialystok, Poland
      • Ciechocinek, Poland
      • Gniewkowo, Poland
      • Grudziadz, Poland
      • Katowice, Poland
      • Krakow, Poland
      • Lublin, Poland
      • Plock, Poland
      • Poznan, Poland
      • Rzeszow, Poland
      • Slawkow, Poland
      • Torun, Poland
      • Warszawa, Poland
      • Wroclaw, Poland
  • Russian Federation
      • Arkhangelsk, Russian Federation
      • Chelyabinsk, Russian Federation
      • Ekaterinburg, Russian Federation
      • Kemerovo, Russian Federation
      • Kirov, Russian Federation
      • Kursk, Russian Federation
      • Moscow, Russian Federation
      • Moscow N/A, Russian Federation
      • Nizhny Novgorod, Russian Federation
      • Novosibirsk, Russian Federation
      • Omsk, Russian Federation
      • Penza, Russian Federation
      • Rostov-On-Don, Russian Federation
      • Russia, Russian Federation
      • Ryazan, Russian Federation
      • Saint Petersburg, Russian Federation
      • Saint-Petersburg, Russian Federation
      • Saratov, Russian Federation
      • Smolensk, Russian Federation
      • St Petersburg, Russian Federation
      • Tomsk, Russian Federation
      • Tula, Russian Federation
      • Tyumen, Russian Federation
      • Yaroslavl, Russian Federation
      • Yaroslavl Nap, Russian Federation
  • Spain
      • Alicante, Spain
      • Almeria, Spain
      • Barcelona, Spain
      • Figueres, Spain
      • Madrid, Spain
      • Málaga, Spain
      • Oviedo, Spain
      • Reus, Spain
      • Sabadell, Spain
      • San Juan De Alicante, Spain
      • Santiago De Compostela, Spain
      • Sevilla N/A, Spain
      • Valencia, Spain
      • Viladecans, Spain
  • Sweden
      • Borås, Sweden
      • Göteborg, Sweden
      • Helsingborg, Sweden
      • Lund, Sweden
      • Malmö, Sweden
      • Oskarshamn N/A, Sweden
      • Piteå, Sweden
      • Stockholm, Sweden
      • Uddevalla, Sweden
  • Ukraine
      • Dnepropetrovsk, Ukraine
      • Donetsk, Ukraine
      • Kharkov, Ukraine
      • Kiev, Ukraine
      • Kyiv, Ukraine
      • Odessa, Ukraine
      • Ternopol, Ukraine
      • Uzhgorod, Ukraine
      • Vinnitsa, Ukraine
      • Zaporozhye, Ukraine
  • United Kingdom
      • Belfast, United Kingdom
      • Blackburn, United Kingdom
      • Bolton, United Kingdom
      • Chorley, United Kingdom
      • Derby, United Kingdom
      • Glasgow, United Kingdom
      • Hull, United Kingdom
      • Leicester, United Kingdom
      • Liverpool, United Kingdom
      • London, United Kingdom
      • Londonderry, United Kingdom
      • Manchester, United Kingdom
      • Randalstown, United Kingdom
      • Salford, United Kingdom
      • York, United Kingdom
  • United States
    • Alabama
      • Birmingham, Alabama, United States
    • Arizona
      • Mesa, Arizona, United States
      • Tucson, Arizona, United States
    • California
      • La Mesa, California, United States
      • Los Gatos, California, United States
      • Pismo Beach, California, United States
      • Stockton, California, United States
      • Walnut Creek, California, United States
    • Florida
      • Doral, Florida, United States
      • Fort Lauderdale, Florida, United States
      • Jacksonville, Florida, United States
      • Miami, Florida, United States
      • Plantation, Florida, United States
    • Georgia
      • Atlanta, Georgia, United States
      • Duluth, Georgia, United States
    • Idaho
      • Boise, Idaho, United States
      • Eagle, Idaho, United States
      • Meridian, Idaho, United States
    • Illinois
      • Peoria, Illinois, United States
    • Kansas
      • Topeka, Kansas, United States
    • Kentucky
      • Crestview Hills, Kentucky, United States
      • Lexington, Kentucky, United States
    • Maine
      • Auburn, Maine, United States
      • Scarborough, Maine, United States
    • Maryland
      • Oxon Hill, Maryland, United States
    • Michigan
      • Royal Oak, Michigan, United States
    • Missouri
      • Kansas City, Missouri, United States
      • Saint Louis, Missouri, United States
    • Nebraska
      • Omaha, Nebraska, United States
    • New Jersey
      • Camden, New Jersey, United States
    • New York
      • Bronx, New York, United States
      • Flushing, New York, United States
    • North Carolina
      • Chapel Hill, North Carolina, United States
      • Charlotte, North Carolina, United States
    • Ohio
      • Cincinnati, Ohio, United States
      • Cleveland, Ohio, United States
      • Columbus, Ohio, United States
      • Gallipolis, Ohio, United States
      • Mentor, Ohio, United States
      • Toledo, Ohio, United States
    • Pennsylvania
      • Beaver, Pennsylvania, United States
      • Norristown, Pennsylvania, United States
      • Sayre, Pennsylvania, United States
    • South Carolina
      • Greenville, South Carolina, United States
    • Tennessee
      • Kingsport, Tennessee, United States
    • Texas
      • Dallas, Texas, United States
      • Houston, Texas, United States
      • Odessa, Texas, United States
      • San Antonio, Texas, United States
      • Temple, Texas, United States
    • Utah
      • Draper, Utah, United States
      • Salt Lake City, Utah, United States
      • Sandy, Utah, United States
      • West Jordan, Utah, United States
    • Virginia
      • Danville, Virginia, United States
      • Richmond, Virginia, United States
    • Washington
      • Spokane, Washington, United States
      • Tacoma, Washington, United States

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients must have a diagnosis of type 2 diabetes mellitus and greater than or equal to (>=) 30 yrs old with history of cardiovascular (CV) event, or >= 50 yrs old with high risk of CV events
  • Patients must have inadequate diabetes control (as defined by glycosylated hemoglobin greater than or equal to 7.0% to less than or equal to 10.5% at screening) and be either (1) not currently on diabetes drug therapy or (2) on therapy with any approved class of diabetes drugs

Exclusion Criteria:

  • A 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 (ie, very low blood sugar) episode within 6 months before screening

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
PLACEBO_COMPARATOR: Placebo
Each patient will receive placebo (inactive medication) on background standard of care for diabetes once daily for the duration of the study
Drug: Placebo
One placebo capsule taken orally (by mouth) once daily
EXPERIMENTAL: Canagliflozin (JNJ-28431754) 100 mg
Each patient will receive canagliflozin (JNJ-28431754) 100 mg once daily on background standard of care for diabetes once daily for the duration of the study
Drug: Canagliflozin (JNJ-28431754) 100 mg
One 100 mg capsule taken orally (by mouth) once daily
EXPERIMENTAL: Canagliflozin (JNJ-28431754) 300 mg
Each patient will receive canagliflozin (JNJ-28431754) 300 mg once daily on background standard of care for diabetes once daily for the duration of the study
Drug: Canagliflozin (JNJ-28431754) 300 mg
One 300 mg capsule taken orally (by mouth) once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Major Adverse Cardiovascular Events (MACE) Composite of Cardiovascular (CV) Death, Non-Fatal Myocardial Infarction (MI), and Non-Fatal Stroke
Time Frame: Up to approximately 8 years
MACE, defined as a composite of CV death, non-fatal MI, and nonfatal stroke. Adjudication of these events by the Endpoint Adjudication Committee (EAC) was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of MACE are presented.
Up to approximately 8 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Homeostasis Model Assessment 2 Steady-State Beta-Cell Function (HOMA2-%B) at the End-of-Treatment (EOT)
Time Frame: Baseline and end of treatment (approximately 338 weeks)
The homeostatic model assessment (HOMA) quantifies insulin resistance and beta-cell function. HOMA2-%B is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady-state beta cell function (%B) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100 percent.
Baseline and end of treatment (approximately 338 weeks)
Percentage of Participants With Progression of Albuminuria at the End-of-Treatment
Time Frame: End of treatment (approximately 338 weeks)
Progression defined as the development of micro-albuminuria (albumin/creatinine ratio (ACR) greater than or equal to [>=] 30 milligram per gram (mg/g) and less than or equal to <= 300 mg/g) or macroalbuminuria (ACR of >300 mg/g) in a participant with baseline normoalbuminuria or the development of macro-albuminuria in a participant with baseline microalbuminuria. Percentage of participants with progression of albuminuria at the end-of-treatment were assessed.
End of treatment (approximately 338 weeks)
Change From Baseline in Proinsulin/Insulin (PI/I) Ratio at the End-of-Treatment
Time Frame: Baseline and end of treatment (approximately 338 weeks)
A raised proinsulin-to-insulin ratio due to impaired processing of proinsulin is an early marker of beta cell dysfunction. Beta-cell dysfunction was evaluated by calculating the PI/I ratio, which estimates the capacity of beta cells to convert proinsulin to insulin and may represent an acceptable method to indicate the degree of beta-cell secretion.
Baseline and end of treatment (approximately 338 weeks)
Change From Baseline in Urinary Albumin/Creatinine Ratio at End-of-Treatment
Time Frame: Baseline and End of treatment (approximately 338 weeks)
Urinary Albumin/Creatinine Ratio is a potential marker of chronic kidney disease, calculated as a ratio of Urinary Albumin and Urinary Creatinine.
Baseline and End of treatment (approximately 338 weeks)
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at End-of-Treatment
Time Frame: Baseline and end of treatment (approximately 338 weeks)
Change from baseline in Estimated Glomerular Filtration Rate (eGFR) was assessed at end of treatment. GFR is a measure of the rate at which blood is filtered by the kidney. Modification of Diet in Renal Disease (MDRD) is an equation (calculation) used to estimate GFR in participants with impaired renal function based on serum creatinine, age, race, and sex. eGFR milliliters/minute/1.73 meters square (mL/min/1.73 m^2) = 175 * (serum creatinine) ^ 1.154 * (Age) ^-0.203 *(0.742 if female) * (1.21 if Black).
Baseline and end of treatment (approximately 338 weeks)
Change From Baseline in Glycated Hemoglobin (HbA1c) at End-of-Treatment
Time Frame: Baseline and end of treatment (approximately 338 weeks)
Change from baseline in glycated hemoglobin (HbA1c) percentage (%) was assessed at end of treatment. Glycated hemoglobin is a form of hemoglobin that is measured primarily to identify the average glucose concentration in the blood.
Baseline and end of treatment (approximately 338 weeks)
Change From Baseline in Fasting Plasma Glucose (FPG) Levels at End-of-Treatment
Time Frame: Baseline and end of treatment (approximately 338 weeks)
Change from baseline in the fasting plasma glucose levels at end-of-treatment was assessed.
Baseline and end of treatment (approximately 338 weeks)
Percent Change From Baseline in Body Weight at End-of-Treatment
Time Frame: Baseline and end of treatment (approximately 338 weeks)
Percent change from baseline in body weight was assessed at the end of treatment.
Baseline and end of treatment (approximately 338 weeks)
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at End-of-Treatment
Time Frame: Baseline and end of treatment (approximately 338 weeks)
Change from baseline in systolic blood pressure and diastolic blood pressure was assessed.
Baseline and end of treatment (approximately 338 weeks)
Change From Baseline in Triglycerides Levels at End-of-Treatment
Time Frame: Baseline and end of treatment (approximately 338 weeks)
Change from baseline in triglycerides levels was assessed.
Baseline and end of treatment (approximately 338 weeks)
Change From Baseline in Cholesterol, High-Density Lipoprotein Cholesterol (HDL-C) and Low Density Lipoprotein Cholesterol (LDL-C) Levels at End-of-Treatment
Time Frame: Baseline and end of treatment (approximately 338 weeks)
Change from baseline in cholesterol, high-density lipoprotein cholesterol and low density lipoprotein cholesterol levels were assessed.
Baseline and end of treatment (approximately 338 weeks)
Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) to High-Density Lipoprotein-Cholesterol (HDL-C) Ratio at End-of-Treatment
Time Frame: Baseline and end of treatment (approximately 338 weeks)
Change from baseline in LDL-C to HDL-C ratio was assessed.
Baseline and end of treatment (approximately 338 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Janssen Research & Development, LLC

Collaborators

The George Institute for Global Health, Australia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

December 9, 2009

Primary Completion (ACTUAL)

February 22, 2017

Study Completion (ACTUAL)

February 22, 2017

Study Registration Dates

First Submitted

December 10, 2009

First Submitted That Met QC Criteria

December 14, 2009

First Posted (ESTIMATE)

December 15, 2009

Study Record Updates

Last Update Posted (ACTUAL)

December 7, 2018

Last Update Submitted That Met QC Criteria

November 5, 2018

Last Verified

November 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CR016627
  • 28431754DIA3008 (OTHER: Janssen Research & Development, LLC)
  • 2009-012140-16 (EUDRACT_NUMBER)

Drug and device information, study documents

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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