A Study to Evaluate the Efficacy and Safety of the Addition of Canagliflozin in Participants With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin and Sitagliptin

Phase 4

Completed

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

• Registration Number: NCT02025907
• Lead Sponsor: Janssen Research & Development, LLC

Brief Summary

The purpose of this study is to assess the effect of canagliflozin (JNJ-28431754) compared to placebo in the treatment of participants with Type 2 Diabetes Mellitus (T2DM), who have inadequate glycemic control on maximally or near-maximally effective doses of metformin and sitagliptin.

Detailed Description

This is a randomized (the study medication is assigned by chance), double-blind (neither physician nor participant knows the identity of the assigned treatment), placebo-controlled (an inactive substance that is compared with a study drug, to test whether the study drug has a real effect), multicenter study of efficacy, safety, and tolerability of canagliflozin in participants with T2DM, who have inadequate glycemic (blood sugar) control on maximally or near-maximally effective doses of metformin \>=1500 mg/day and sitagliptin 100 mg/day. Approximately 200 participants will be randomly assigned to 1 of 2 treatment groups in 1:1 ratio for 26 weeks. During the study the participants will be also provided with diet and exercise counseling (standardized non-pharmacological therapy).

Study Timeline

• Study First Submitted: 2013-12-30
• Study First Submitted QC: 2013-12-30
• Study First Posted: 2014-01-01
• Study Start: 2014-02
• Primary Completion: 2015-09
• Study Completion: 2015-09
• Results First Submitted: 2016-07-22
• Results First Submitted QC: 2016-07-22
• Results First Posted: 2016-09-02
• Status Verified: 2016-10
• Last Update Submitted: 2016-10-28
• Last Update Posted: 2016-10-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 218

Inclusion Criteria

• Must have a diagnosis of type 2 diabetes mellitus
• Must have a screening HbA1c of >=7.5% to <=10.5%
• Must be on metformin >=1500 mg/day and sitagliptin 100 mg/day (or equivalent fixed dose combination) at a stable dose for at least 12 weeks before screening

Exclusion Criteria

• History of diabetic ketoacidosis or T1DM, hereditary glucose-galactose malabsorption or primary renal glycosuria
• A myocardial infarction, unstable angina, revascularization procedure or cerebrovascular accident within 12 weeks before screening
• eGFR <60 ml/min/1.73m2, or serum creatinine >=1.4 mg/dL for men and >=1.3 mg/dL for women
• Known significant liver disease (eg, acute hepatitis, chronic active hepatitis, cirrhosis)
• Major surgery (ie, requiring general anesthesia) within 12 weeks before screening

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Each participant will receive placebo (inactive medication) once daily for 28 weeks.
Canagliflozin (JNJ-28431754)	Canagliflozin, 300 mg	Each participant will receive canagliflozin (JNJ-28431754) 100 mg once daily during the first 6 weeks, then the dose may be increased to 300 mg once daily.
Canagliflozin (JNJ-28431754)	Canagliflozin, 100 mg	Each participant will receive canagliflozin (JNJ-28431754) 100 mg once daily during the first 6 weeks, then the dose may be increased to 300 mg once daily.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26	Baseline and Week 26

Secondary Outcome Measures

Name	Time	Method
Percent Change From Baseline in Body Weight at Week 26	Baseline and Week 26
Percentage of Participants With HbA1c Less Than (<) 7.0 Percent at Week 26	Week 26
Change From Baseline in Systolic Blood Pressure (SBP) at Week 26	Baseline and Week 26
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26	Baseline and Week 26