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

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ClinicalTrials.gov Identifier: NCT01989754
Recruitment Status : Completed
First Posted : November 21, 2013
Last Update Posted : February 22, 2018
Sponsor:
Collaborator:
The George Institute for Global Health, Australia
Information provided by (Responsible Party):
Janssen Research & Development, LLC

October 17, 2013
November 21, 2013
February 22, 2018
January 16, 2014
February 23, 2017   (Final data collection date for primary outcome measure)
Time to First Occurrence of Progression of Albuminuria [ Time Frame: Baseline, Week 26, 52, 78, 104, 156 ]
Progression of albuminuria is defined as the development of microalbuminuria or macroalbuminuria in a participant with baseline normoalbuminuria or the development of macroalbuminuria in a participant with baseline microalbuminuria, accompanied by an urinary albumin/creatinine ratio (ACR) value increase of greater than or equal to 30% from baseline.
Number of participants with progression of albuminuria [ Time Frame: up to Week 156 ]
Progression of albuminuria is defined as the development of microalbuminuria or macroalbuminuria in a participant with baseline normoalbuminuria or the development of macroalbuminuria in a participant with baseline microalbuminuria, accompanied by an urinary albumin/creatinine ratio (ACR) value increase of greater than or equal to 30% from baseline.
Complete list of historical versions of study NCT01989754 on ClinicalTrials.gov Archive Site
  • Composite Endpoint of Death From Cardiovascular (CV) Causes or Hospitalization for Heart Failure [ Time Frame: Baseline, time to event up to end of study (approximately 3 years) ]
  • Death from CV Causes [ Time Frame: Baseline, time to event up to end of study (approximately 3 years) ]
  • Number of participants with regression of albuminuria [ Time Frame: Baseline, Week 26, 52, 78, 104, 156 ]
    Regression of albuminuria is defined as the development of normoalbuminuria in a participant with baseline microalbuminuria or macroalbuminuria, or the development of microalbuminuria in a participant with baseline macroalbuminuria, accompanied by a decrease in the urinary ACR value of greater than or equal to 30% from baseline.
  • Change in estimated glomerular filtration rate (eGFR) from baseline to the last off-treatment measurement [ Time Frame: Baseline, up to Day 30 of post treatment follow-up ]
  • Urinary albumin/creatinine ratio at last on-treatment visit [ Time Frame: Baseline, Week 156 ]
Major adverse cardiovascular (CV) events [ Time Frame: Baseline, time to event up to end of study (approximately 3 years) ]
Cardiovascular safety data from this study will be combined with the data from the other large-scale study of the effects of canagliflozin compared to placebo (CANVAS) in a pre-specified meta-analysis of cardiovascular safety outcomes. Cardiovascular safety data will be evaluated as the time to first occurrence of major adverse cardiovascular events, including CV death, nonfatal myocardial infarction (MI), and nonfatal stroke.
Major adverse cardiovascular (CV) events [ Time Frame: up to Week 156 ]
Cardiovascular safety data will be evaluated as the number of major adverse cardiovascular events, including CV death, nonfatal myocardial infarction (MI), and nonfatal stroke.
 
A Study of the Effects of Canagliflozin (JNJ-28431754) on Renal Endpoints in Adult Participants With Type 2 Diabetes Mellitus
A Randomized, Multicenter, Double-Blind, Parallel, Placebo-Controlled Study of the Effects of Canagliflozin on Renal Endpoints in Adult Subjects With Type 2 Diabetes Mellitus
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.

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.

Interventional
Phase 4
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Diabetes Mellitus, Type 2
  • Albuminuria
  • Drug: Placebo
    One placebo capsule taken orally (by mouth) once daily for 156 weeks
  • Drug: Canagliflozin, 100 mg
    One 100 mg capsule taken orally (by mouth) once daily
  • Drug: Canagliflozin, 300 mg
    One 300 mg capsule taken orally (by mouth) once daily
  • Experimental: 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.
    Interventions:
    • Drug: Canagliflozin, 100 mg
    • Drug: Canagliflozin, 300 mg
  • Placebo Comparator: Placebo
    Each patient will receive placebo (inactive medication) once daily.
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
5813
5700
February 23, 2017
February 23, 2017   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
30 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Argentina,   Australia,   Belgium,   Brazil,   Canada,   China,   Czechia,   France,   Germany,   Hungary,   Korea, Republic of,   Malaysia,   Mexico,   Netherlands,   New Zealand,   Poland,   Puerto Rico,   Russian Federation,   Spain,   Sweden,   Taiwan,   Ukraine,   United Kingdom,   United States
Czech Republic
 
NCT01989754
CR102647
2013-003050-25 ( EudraCT Number )
28431754DIA4003 ( Other Identifier: Janssen Research & Development, LLC )
Yes
Studies a U.S. FDA-regulated Device Product: No
Not Provided
Janssen Research & Development, LLC
Janssen Research & Development, LLC
The George Institute for Global Health, Australia
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
Janssen Research & Development, LLC
February 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP