CANagliflozin Treatment And Trial Analysis-Sulfonylurea (CANTATA-SU) SGLT2 Add-on to Metformin Versus Glimepiride

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate the efficacy, safety, and tolerability of canagliflozin (JNJ-28431754) compared with glimepiride in patients with type 2 diabetes mellitus with inadequate control despite treatment with metformin.

Detailed Description
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Type 2 diabetes mellitus (T2DM) is well recognized as a major public health problem that presents patients with a significant risk of complications including heart disease, retinopathy, nephropathy, and neuropathy. Various classes of orally administered antihyperglycemic agents have been developed for the treatment of diabetes and although individual agents may be highly effective for some patients, it is still difficult to maintain optimal glycemic control in most patients, thereby resulting in high rates of morbidity and mortality in the diabetic population. This is a randomized, double-blind, active comparator-controlled, 3-arm, parallel-group, multicenter study to demonstrate the efficacy, safety, and tolerability of canagliflozin compared with a sulfonylurea (glimepiride) in patients with T2DM, 18 to 80 years of age, inclusive, who are not optimally controlled on metformin monotherapy. The primary study hypothesis is that the study drug will be non-inferior to glimepiride as assessed by the change in hemoglobin A1c (HbA1c) from baseline. The patients will receive capsules taken by mouth of canagliflozin (either 100 or 300 mg), or glimepiride with a starting dosage of 1 mg, which will be increased to a maximum dose of 6 or 8 mg once daily for a total duration of 104 weeks.

Official Title
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A Randomized, Double-Blind, 3-Arm Parallel-Group, 2-Year (104-Week), Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of JNJ-28431754 Compared With Glimepiride in the Treatment of Subjects With Type 2 Diabetes Mellitus Not Optimally Controlled on Metformin Monotherapy

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Glimepiride
* Drug: Canagliflozin (JNJ-28431754)
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have a diagnosis of type 2 diabetes Body mass index (BMI) >=22 to <=45 kg/m2, at screening Patients must be taking a stable dosage of metformin as monotherapy at screening Patients must have a HbA1c between >=7% and <=9.5% at Week 2 Patients must have a fasting plasma glucose (FPG) <=270 mg/dL (15 mmol/L) at Week -2 Exclusion Criteria: Patients having prior exposure or known contraindication or suspected hypersensitivity to JNJ-28431754, glimepiride, or metformin History of diabetic ketoacidosis or type 1 diabetes mellitus History of pancreas or beta-cell transplantation History of active proliferative diabetic retinopathy History of hereditary glucose-galactose malabsorption or primary renal glucosuria Renal disease requiring treatment with immunosuppressive therapy within the past 12 months before screening or a history of dialysis or renal transplant Taken thiazolidinedione therapy in the past 16 weeks before screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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 |
| --- | --- |
| Active Comparator: Glimepiride<br>Each patient will receive glimepiride, at protocol-specified doses, once daily in combination with protocol-specified doses of metformin for 104 weeks. | Drug: Glimepiride<br>* Glimepiride will be given orally (by mouth), as over-encapsulated tablets, starting at a dose of 1mg once daily and increasing to a maximum of 6 mg or 8 mg once daily for 104 weeks.<br>* Other names: sulfonylurea;Drug: Metformin<br>* Metformin will be given orally at the protocol-specified dose for 104 weeks.<br>|
| Experimental: Canagliflozin 100 mg<br>Each patient will receive 100 mg of canagliflozin (JNJ-28431754) once daily with protocol-specified doses of metformin for 104 weeks. | Drug: Canagliflozin (JNJ-28431754)<br>* Canagliflozin (JNJ-28431754) will be given orally as over-encapsulated tablets, at a dose of 100 mg or 300 mg once daily for 104 weeks.<br>Drug: Metformin<br>* Metformin will be given orally at the protocol-specified dose for 104 weeks.<br>|
| Experimental: Canagliflozin 300 mg<br>Each volunteer will receive 300 mg of canagliflozin (JNJ-28431754) once daily with protocol-specified doses of metformin for 104 weeks. | Drug: Canagliflozin (JNJ-28431754)<br>* Canagliflozin (JNJ-28431754) will be given orally as over-encapsulated tablets, at a dose of 100 mg or 300 mg once daily for 104 weeks.<br>Drug: Metformin<br>* Metformin will be given orally at the protocol-specified dose for 104 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c From Baseline to Week 52 | The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 52 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus glimepiride) in the LS mean change. | Day 1 (Baseline) and Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Experiencing at Least 1 Hypoglycemic Event From Baseline to Week 52 | The table below shows the percentage of patients who experienced at least 1 documented hypoglycemic event from Baseline to Week 52 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus glimepiride) in percentages. | Day 1 (Baseline) and Week 52 | 
| Percent Change in Body Weight From Baseline to Week 52 | The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 52 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus glimepiride) in the LS mean percent change. | Day 1 (Baseline) and Week 52 | 
| Change in HbA1c From Baseline to Week 104 | The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 104 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus glimepiride) in the LS mean change. | Baseline, Week 104 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Metformin, Glimepiride, Hemoglobin A1c, Type 2 diabetes mellitus, Canagliflozin