A Efficacy, Safety, and Tolerability Study of Canagliflozin in Patients With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin Alone or in Combination With a Sulphonylurea

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety, tolerability, and efficacy of the addition of canagliflozin relative to the addition of placebo in patients with inadequate glycemic control on metformin alone or in combination with a sulphonylurea.

Detailed Description
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This is a double-blind (neither study staff or the patient will know the identity of the treatment assigned) study of canagliflozin where Chinese and other Asian adult patients with Type 2 Diabetes Mellitus (T2DM) who have inadequate glycemic control on metformin alone or in combination with a sulphonylurea (SU) will be randomized (assigned to 1 of 3 treatments by chance) to receive the addition of treatment with canagliflozin 100 mg once daily, canagliflozin 300 mg once daily, or matching placebo capsules (placebo is a treatment identical in appearance to canagliflozin but does not contain active drug). All patients will take orally (by mouth) 1 single-blind placebo capsule once daily before the first meal of the day for up to 2 weeks (last dose of single-blind placebo to be taken the day before the baseline (Day 1) visit. On Day 1, patients will take orally, once daily 1 capsule of canagliflozin 100 mg, canagliflozin 300 mg, or placebo before the first meal of the day for up to 18 weeks.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, 18-Week 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 Alone or in Combination With a Sulphonylurea

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Placebo
* Drug: Canagliflozin 100mg
* Drug: Canagliflozin 300mg
* Drug: Metformin
* Drug: Sulphonylurea


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with T2DM with inadequate glycemic control on metformin monotherapy or on metformin in combination with an SU at protocol-specified doses and having HbA1c >=7.0% and <=10.5% at Week -2 are eligible for enrollment in the study. Exclusion Criteria: History of diabetic ketoacidosis, type 1 diabetes mellitus (T1DM), pancreas or beta cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy Has repeated (ie, 2 or more over a 1-week period) fasting plasma glucose (FPG) and/or fasting self-monitored blood glucose (SMBG) measurements >=270 mg/dL (15 mmol/L) during the pre-treatment phase, despite reinforcement of diet and exercise counseling History of a severe hypoglycemic episode within 6 months before screening History of or current illness considered to be clinically significant by the investigator

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Canagliflozin 100mg<br>Each participant will receive 100 mg of canagliflozin once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea. | Drug: Canagliflozin 100mg<br>* Type=1, unit=mg, number=100, form=capsule, route=oral use. One capsule once daily for up to 18 weeks after completing a single-blind placebo run-in period (1 placebo capsule once daily for up to 2 weeks).<br>Drug: Metformin<br>* The participant's stable dose of background therapy of metformin should be continued throughout the study.<br>Drug: Sulphonylurea<br>* The participant's stable dose of background therapy of metformin plus sulphonylurea should be continued throughout the study.<br>|
| Experimental: Canagliflozin 300mg<br>Each participant will receive 300 mg of canagliflozin once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea. | Drug: Canagliflozin 300mg<br>* Type=1, unit=mg, number=300, form=capsule, route=oral use. One capsule once daily for up to 18 weeks after completing a single-blind placebo run-in period (1 placebo capsule once daily for up to 2 weeks).<br>Drug: Metformin<br>* The participant's stable dose of background therapy of metformin should be continued throughout the study.<br>Drug: Sulphonylurea<br>* The participant's stable dose of background therapy of metformin plus sulphonylurea should be continued throughout the study.<br>|
| Placebo Comparator: Placebo<br>Each participant will receive matching placebo once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea. | Drug: Placebo<br>* Form=capsule, route=oral administration. One capsule once daily for up to 18 weeks after completing a single-blind placebo run-in period (1 placebo capsule once daily for up to 2 weeks).<br>Drug: Metformin<br>* The participant's stable dose of background therapy of metformin should be continued throughout the study.<br>Drug: Sulphonylurea<br>* The participant's stable dose of background therapy of metformin plus sulphonylurea 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 Glycosylated Hemoglobin (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 Glycosylated Hemoglobin (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. | Day 1 (Baseline) and Week 18 | 
| Percentage of Patients With Glycosylated Hemoglobin (HbA1c) <6.5% at Week 18 | The table below shows the percentage of patients with HbA1c <6.5% at Week 18 in each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the percentage. | Day 1 (Baseline) and Week 18 | 

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