The CANTATA-D2 Trial (CANagliflozin Treatment And Trial Analysis - DPP-4 Inhibitor Second Comparator Trial)

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 canagliflozin compared with sitagliptin in patients with type 2 diabetes mellitus who are receiving treatment with metformin and sulphonylurea and have inadequate glycemic (blood sugar) control.

Detailed Description
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Canagliflozin is a drug that is being tested to see if it may be useful in treating patients diagnosed with type 2 diabetes mellitus (T2DM). This is a randomized (study drug assigned by chance), double-blind (neither the patient or the study doctor will know the name of the assigned treatment), multicenter study to determine the efficacy, safety, and tolerability of canagliflozin 300 mg compared to sitagliptin 100 mg (an antihyperglycemic drug) in patients with T2DM who are not achieving an adequate response from current antihyperglycemic therapy with metformin and sulphonylurea to control their diabetes. Approximately 720 patients with T2DM who are receiving combination therapy with metformin and sulphonylurea will receive the addition of once-daily treatment with canagliflozin 300 mg or sitagliptin 100 mg capsules for 52 weeks. Patients will participate in the study for approximately 59 to 72 weeks. During treatment, patients will be monitored for safety by review of adverse events, results from laboratory tests, 12-lead electrocardiograms (ECGs), vital signs measurements, body weight, physical examinations, and self monitored blood glucose (SMBG) measurements. The primary outcome measure in the study is the effect of canagliflozin compared to sitagliptin on hemoglobin A1c (HbA1c) after 52 weeks of treatment. Study drug will be taken orally (by mouth) once daily before the first meal each day unless otherwise specified. Patients will take single-blind placebo for 2 weeks before randomization. After randomization, patients in the study will take double-blind canagliflozin 300 mg or matching sitagliptin 100 mg for 52 weeks.

Official Title
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A Randomized, Double-Blind, Active-Controlled, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of Canagliflozin Versus Sitagliptin in the Treatment of Subjects With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin and Sulphonylurea Therapy

Conditions
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Diabetes Mellitus, Type 2

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


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 and sulphonylurea Patients in the study must have a HbA1c between >=7 and <=10.5% and a fasting plasma glucose (FPG) <300 mg/dL (16.7 mmol/L) Exclusion Criteria: History of diabetic ketoacidosis, type 1 diabetes mellitus (T1DM), pancreas or beta cell transplantation, or 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

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Canagliflozin 300 mg<br>Each patient will receive 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea | Drug: Canagliflozin 300 mg<br>* One 300 mg capsule once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea<br>Drug: Metformin<br>* Patients will continue to take background therapy with Metformin for T2DM at maximally or near-maximally effective protocol-specified doses for the duration of the study.<br>Drug: Sulphonylurea<br>* Patients will continue to take background therapy with Sulphonylurea for T2DM at maximally or near-maximally effective protocol-specified doses for the duration of the study.<br>|
| Active Comparator: Sitagliptin 100 mg<br>Each patient will receive 100 mg of sitagliptin once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea | Drug: Sitagliptin 100 mg<br>* One 100 mg capsule once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea<br>Drug: Metformin<br>* Patients will continue to take background therapy with Metformin for T2DM at maximally or near-maximally effective protocol-specified doses for the duration of the study.<br>Drug: Sulphonylurea<br>* Patients will continue to take background therapy with Sulphonylurea for T2DM at maximally or near-maximally effective protocol-specified doses for the duration of 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 52 | The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 52 for each treatment group. The statistical analysis shows the treatment difference (ie, between canagliflozin and sitagliptin) in the LS mean change. | Day 1 (Baseline) and Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With HbA1c <7% at Week 52 | The table below shows the percentage of patients with HbA1c <7% at Week 52 in each treatment group. The statistical analysis shows the treatment difference (ie, between canagliflozin and sitagliptin) in the percentage. | Week 52 | 
| Change in Fasting Plasma Glucose (FPG) From Baseline to Week 52 | The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 52 for each treatment group. The statistical analysis shows the treatment difference (ie, between canagliflozin and sitagliptin) in the LS mean change. | 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 analysis shows the treatment difference (ie, between canagliflozin and sitagliptin) in the LS mean percent change. | Day 1 (Baseline) and Week 52 | 
| Change in Systolic Blood Pressure (SBP) From Baseline to Week 52 | The table below shows the least-squares (LS) mean change in SBP from Baseline to Week 52 for each treatment group. The statistical analysis shows the treatment difference (ie, between canagliflozin and sitagliptin) in the LS mean change. | Day 1 (Baseline) and Week 52 | 
| Percent Change in Triglycerides From Baseline to Week 52 | The table below shows the mean percent change in triglycerides from Baseline to Week 52 for each treatment group. The statistical analysis shows the treatment difference (ie, between canagliflozin and sitagliptin) in the LS mean change. | Day 1 (Baseline) and Week 52 | 
| Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 52 | The table below shows the mean percent change in HDL-C from Baseline to Week 52 for each treatment group. The statistical analysis shows the treatment difference (ie, between canagliflozin and sitagliptin) in the LS mean change. | Day 1 (Baseline) and Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Canagliflozin, Sitagliptin (Januvia), Metformin, Sulphonylurea, Hemoglobin A1c, Type 2 diabetes mellitus