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

Study Overview
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Brief Summary
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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
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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).

Official Title
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A Randomized, Double-blind, Placebo Controlled, 2-arm, Parallel-group, 26-week, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of Canagliflozin in the Treatment of Subjects With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin and Sitagliptin Therapy

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Canagliflozin, 100 mg
* Drug: Canagliflozin, 300 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Canagliflozin (JNJ-28431754)<br>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. | Drug: Canagliflozin, 100 mg<br>* One 100 mg capsule taken orally (by mouth) once daily.<br>Drug: Canagliflozin, 300 mg<br>* One 300 mg capsule taken orally (by mouth) once daily.<br>|
| Placebo Comparator: Placebo<br>Each participant will receive placebo (inactive medication) once daily for 28 weeks. | Drug: Placebo<br>* One placebo capsule taken orally (by mouth) once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26 |  | Baseline and Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 |  | Baseline and Week 26 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sitagliptin, Diabetes Mellitus, Type 2, Canagliflozin, Hemoglobin A1c, Metformin, T2DM, JNJ-28431754