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

Phase 4

Completed

• Conditions: Diabetes Mellitus, Type 2; Albuminuria
• Interventions: Drug: Canagliflozin, 100 mg; Drug: Placebo; Drug: Canagliflozin, 300 mg

• Registration Number: NCT01989754
• Lead Sponsor: Janssen Research & Development, LLC

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2013-10-17
• Study First Submitted QC: 2013-11-20
• Study First Posted: 2013-11-21
• Study Start: 2014-01-16
• Primary Completion: 2017-02-23
• Study Completion: 2017-02-23
• Disposition First Submitted: 2018-02-20
• Disposition First Submitted QC: 2018-02-20
• Disposition First Posted: 2018-02-22
• Status Verified: 2018-11
• Results First Submitted: 2018-11-19
• Results First Submitted QC: 2018-11-19
• Last Update Submitted: 2018-11-19
• Results First Posted: 2018-12-11
• Last Update Posted: 2018-12-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 5813

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.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Canagliflozin (JNJ-28431754)	Canagliflozin, 100 mg	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.
Canagliflozin (JNJ-28431754)	Canagliflozin, 300 mg	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.
Placebo	Placebo	Each patient will receive placebo (inactive medication) once daily.

Primary Outcome Measures

Name	Time	Method
Progression of Albuminuria	Up to 3 years	Progression defined as the development of micro-albuminuria (Urine Albumin Creatinine Ratio \[UACR\] 30 to 300 milligram per gram \[mg/g\]) or macroalbuminuria (Albumin/creatinine ratio \[ACR\] of greater than \[\>\] 300 mg/g) in a participant with baseline normoalbuminuria (ACR less than \[\<\] 30 mg/g) or the development of macro-albuminuria in a participant with baseline microalbuminuria with an ACR increase greater than or equal to (\>=) 30 percent from baseline. Participants with macroalbuminuria at baseline (ACR\>300 mg/g) were excluded from the analysis. Event rate was estimated based on the time to the first occurrence of the event.

Secondary Outcome Measures

Name	Time	Method
Cardiovascular (CV) Death	Approximately 3 years	Analyses were using adjudicated events, i.e. CV death events, and adjudication of these outcomes by the Endpoint Adjudication Committee (EAC) were done in a blinded fashion. Event rate was estimated based on the time to the first occurrence of the event.
Composite of Cardiovascular (CV) Death Events or Hospitalization for Heart Failure	Approximately 3 years	Analyses were using adjudicated events, that is (i.e.) CV death events or hospitalization due to heart failure, and adjudication of these outcomes by the Endpoint Adjudication Committee (EAC) were done in a blinded fashion. Event rate was estimated based on the time to the first occurrence of the event.