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

Phase 3
Completed
Conditions
Diabetes Mellitus, Type 2
Interventions
Registration Number
NCT00968812
Lead Sponsor
Janssen Research & Development, LLC
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1452
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Canagliflozin 300 mgCanagliflozin (JNJ-28431754)Each volunteer will receive 300 mg of canagliflozin (JNJ-28431754) once daily with protocol-specified doses of metformin for 104 weeks.
Canagliflozin 100 mgCanagliflozin (JNJ-28431754)Each patient will receive 100 mg of canagliflozin (JNJ-28431754) once daily with protocol-specified doses of metformin for 104 weeks.
GlimepirideGlimepirideEach patient will receive glimepiride, at protocol-specified doses, once daily in combination with protocol-specified doses of metformin for 104 weeks.
GlimepirideMetforminEach patient will receive glimepiride, at protocol-specified doses, once daily in combination with protocol-specified doses of metformin for 104 weeks.
Canagliflozin 300 mgMetforminEach volunteer will receive 300 mg of canagliflozin (JNJ-28431754) once daily with protocol-specified doses of metformin for 104 weeks.
Canagliflozin 100 mgMetforminEach patient will receive 100 mg of canagliflozin (JNJ-28431754) once daily with protocol-specified doses of metformin for 104 weeks.
Primary Outcome Measures
NameTimeMethod
Change in HbA1c From Baseline to Week 52Day 1 (Baseline) and 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.

Secondary Outcome Measures
NameTimeMethod
Percentage of Patients Experiencing at Least 1 Hypoglycemic Event From Baseline to Week 52Day 1 (Baseline) and 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.

Percent Change in Body Weight From Baseline to Week 52Day 1 (Baseline) and 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.

Change in HbA1c From Baseline to Week 104Baseline, 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.

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