An Efficacy, Safety, and Tolerability Study of Canagliflozin in the Treatment of Patients With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin Monotherapy

Phase 2

Completed

Interventions: Drug: Canagliflozin 150 mg
Drug: Canagliflozin 50 mg
Drug: Placebo
Drug: Metformin

Brief Summary: The purpose of this study is to evaluate the efficacy and safety of 2 different doses of canagliflozin compared with placebo in patients with type 2 diabetes mellitus who are receiving treatment with metformin monotherapy (ie, treatment with a single drug) and have inadequate glycemic (blood sugar) control.

Detailed Description: This is a randomized (study drug assigned by chance), double-blind (neither the patient nor the study doctor will know the identity of assigned study drug), placebo-controlled, parallel-group,3-arm (3 treatment groups) multicenter study to determine the efficacy, safety, and tolerability of canagliflozin compared to placebo (a capsule that is identical in appearance to canagliflozin but does not contain active drug) in patients with type 2 diabetes mellitus (T2DM) who are not achieving an adequate response from current antihyperglycemic therapy with metformin to control their diabetes. Canagliflozin (a Sodium-Glucose Cotransporter 2 inhibitor) is currently under development to lower blood sugar levels in patients with T2DM. Patients will take single-blind placebo capsules orally (by mouth) for 2 weeks before randomization. Patients will be randomly assigned canagliflozin or matching placebo, orally, twice daily, with 1 capsule taken with the morning meal and 1 capsule taken with the evening meal (2 capsules per day) and concurrent with metformin, if applicable, for up to 18 weeks. The dosing time of metformin should remain the same throughout the study.

Recruitment & Eligibility

Inclusion Criteria

All patients must have a diagnosis of T2DM and be currently treated with metformin
Patients in the study must have a HbA1c between >=7 and <=10.5%
Patients must have a fasting plasma glucose (FPG) <270 mg/dL (15 mmol/L)

Exclusion Criteria

History of diabetic ketoacidosis, type 1 diabetes mellitus (T1DM), pancreas or beta cell transplantation, diabetes secondary to pancreatitis or pancreatectomy, or a severe hypoglycemic episode within 6 months before screening

Arm && Interventions

Group	Intervention	Description
Canagliflozin 150 mg bid	Canagliflozin 150 mg	Each patient will receive 150 mg canagliflozin twice daily for 18 weeks
Canagliflozin 50 mg bid	Metformin	Each patient will receive 50 mg canagliflozin twice daily for 18 weeks.
Canagliflozin 50 mg bid	Canagliflozin 50 mg	Each patient will receive 50 mg canagliflozin twice daily for 18 weeks.
Placebo	Placebo	Each patient will receive matching placebo twice daily for 18 weeks
Placebo	Metformin	Each patient will receive matching placebo twice daily for 18 weeks
Canagliflozin 150 mg bid	Metformin	Each patient will receive 150 mg canagliflozin twice daily for 18 weeks

Primary Outcome Measures

Name	Time	Method
Change in HbA1c From Baseline to Week 18	Day 1 (Baseline) and Week 18	The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 18 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.

Secondary Outcome Measures

Name	Time	Method
Percentage of Patients With HbA1c <7% at Week 18	Week 18	The table below shows the percentage of patients with HbA1c \<7% at Week 18 in each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the percentage.
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 18	Day 1 (Baseline) and Week 18	The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 18 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.
Percent Change in Body Weight From Baseline to Week 18	Day 1 (Baseline) and Week 18	The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 18 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean percent change.