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

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 4

Conditions: Albuminuria; Diabetes Mellitus, Type 2

Treatments: Drug: Canagliflozin, 100 mg; Drug: Canagliflozin, 300 mg; Drug: Placebo

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01989754

CR102647

28431754DIA4003 (Other Identifier)

2013-003050-25 (EudraCT Number)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 5,813 patients

Sex: All

Ages: 30+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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5,813 participants in 2 patient groups, including a placebo group

Canagliflozin (JNJ-28431754)

Experimental group

Description:

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.

Treatment:

Drug: Canagliflozin, 300 mg

Drug: Canagliflozin, 100 mg

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo