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CANVAS - CANagliflozin cardioVascular Assessment Study (CANVAS)

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ClinicalTrials.gov Identifier: NCT01032629
Recruitment Status : Completed
First Posted : December 15, 2009
Results First Posted : December 7, 2018
Last Update Posted : December 7, 2018
Sponsor:
Collaborator:
The George Institute for Global Health, Australia
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 2 Cardiovascular Diseases Risk Factors Drug: Placebo Drug: Canagliflozin (JNJ-28431754) 100 mg Drug: Canagliflozin (JNJ-28431754) 300 mg Phase 3

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  (Clinical Trial)
Actual Enrollment : 4330 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : December 9, 2009
Actual Primary Completion Date : February 22, 2017
Actual Study Completion Date : February 22, 2017

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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).

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01032629


  Show 313 Study Locations
Sponsors and Collaborators
Janssen Research & Development, LLC
The George Institute for Global Health, Australia
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  Study Documents (Full-Text)

Documents provided by Janssen Research & Development, LLC:
Study Protocol  [PDF] May 5, 2016
Statistical Analysis Plan  [PDF] March 20, 2017


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01032629     History of Changes
Other Study ID Numbers: CR016627
28431754DIA3008 ( Other Identifier: Janssen Research & Development, LLC )
2009-012140-16 ( EudraCT Number )
First Posted: December 15, 2009    Key Record Dates
Results First Posted: December 7, 2018
Last Update Posted: December 7, 2018
Last Verified: November 2018

Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Janssen Research & Development, LLC:
Diabetes
Type 2 diabetes mellitus
Cardiovascular risk
Cardiovascular outcomes
Canagliflozin (JNJ-28431754)
Placebo

Additional relevant MeSH terms:
Diabetes Mellitus
Cardiovascular Diseases
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Canagliflozin
Hypoglycemic Agents
Physiological Effects of Drugs