The CANTATA-D Trial (CANagliflozin Treatment and Trial Analysis - DPP-4 Inhibitor Comparator Trial)

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 nor the study doctor will know the identity of
assigned study drug), placebo- and active-controlled, parallel-group, 4-arm (4 treatment
groups) multicenter study to determine the efficacy, safety, and tolerability of
canagliflozin (100 mg and 300 mg) compared to placebo (a capsule that looks like all the
other treatments but has no real medicine) and an active-control (sitagliptin 100 mg, an
antihyperglycemic agent) in patients with T2DM who are not achieving an adequate response
from current antihyperglycemic therapy with metformin Immediate Release (IR) to control
their diabetes. Approximately 1,260 patients with T2DM who are receiving treatment with
metformin IR and have inadequate glycemic (blood sugar) will receive once-daily treatment
with canagliflozin (100 mg or 300 mg), sitagliptin 100 mg, or placebo capsules for 26 weeks
(Period I) followed by another 26-weeks where patients treated with canagliflozin (100 mg or
300 mg) or sitagliptin 100 mg will continue treatment for an additional 26 weeks and
patients treated with placebo will be switched to active double-blind treatment with
sitagliptin 100 mg capsules administered once-daily for 26 weeks (Period II). In addition,
all patients will take protocol specified stable doses of metformin IR along with assigned
study drug for the duration of the study. Patients will participate in the study for
approximately 59 to 71 weeks. During the study, if a patient's fasting blood sugar remains
high despite treatment with study drug, metformin IR, and reinforcement with diet and
exercise, the patient will receive treatment with glimepiride (rescue therapy) consistent
with local prescribing information. During treatment, patients will be monitored for safety
by review of adverse events, results from laboratory tests, 12-lead electrocardiograms
(ECGs), vital sign measurements, body weight, physical examinations, and self-monitored
blood glucose (SMGB) measurements. The primary outcome measure in the study is to assess the
effect of canagliflozin relative to placebo on hemoglobin A1c (HbA1c) after 26 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 (100 mg or 300 mg) or sitagliptin 100 mg for 52 weeks OR placebo for 26 weeks
switched to double-blind treatment with sitaliptin 100 mg for 26 weeks.