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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, 3-Arm, Parallel-Group, 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

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Canagliflozin 50 mg
* Drug: Placebo
* Drug: Canagliflozin 150 mg
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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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

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 |
| --- | --- |
| Experimental: Canagliflozin 50 mg bid<br>Each patient will receive 50 mg canagliflozin twice daily for 18 weeks. | Drug: Canagliflozin 50 mg<br>* One canagliflozin 50-mg capsule taken orally twice daily with a meal for 18 weeks<br>Drug: Metformin<br>* The patient's stable daily dose of Metformin background therapy should be continued throughout the study.<br>|
| Experimental: Canagliflozin 150 mg bid<br>Each patient will receive 150 mg canagliflozin twice daily for 18 weeks | Drug: Canagliflozin 150 mg<br>* 1 canagliflozin 150-mg capsule taken orally twice daily with a meal for 18 weeks<br>Drug: Metformin<br>* The patient's stable daily dose of Metformin background therapy should be continued throughout the study.<br>|
| Placebo Comparator: Placebo<br>Each patient will receive matching placebo twice daily for 18 weeks | Drug: Placebo<br>* 1 placebo capsule taken orally twice daily with a meal for 18 weeks<br>Drug: Metformin<br>* The patient's stable daily dose of Metformin background therapy should be continued throughout the study.<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 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. | Day 1 (Baseline) and Week 18 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Fasting Plasma Glucose (FPG) From Baseline to 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. | Day 1 (Baseline) and Week 18 | 
| Percent Change in Body Weight From Baseline to 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. | Day 1 (Baseline) and Week 18 | 
| Percentage of Patients With HbA1c <7% at 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. | Week 18 | 

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