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

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 3

Conditions: Diabetes Mellitus, Type 2

Treatments: Drug: Sitagliptin; Drug: Metformin immediate release; Drug: Canagliflozin; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01106677

28431754DIA3006 (Other Identifier)

CR017023

Details and patient eligibility

About

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

Full description

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.

Enrollment: 1,284 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• All patients must have a diagnosis of T2DM and be currently treated with metformin IR
• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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1,284 participants in 4 patient groups

Canagliflozin 100 mg

Experimental group

Description:

Each patient will receive 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.

Treatment:

Drug: Metformin immediate release

Drug: Canagliflozin

Canagliflozin 300 mg

Experimental group

Description:

Each patient will receive 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.

Treatment:

Drug: Metformin immediate release

Drug: Canagliflozin

Sitagliptin 100 mg

Active Comparator group

Description:

Each patient will receive 100 mg of sitagliptin once daily for 52 weeks with protocol-specified doses of metformin immediate release.

Treatment:

Drug: Metformin immediate release

Drug: Sitagliptin

Placebo/Sitagliptin

Other group

Description:

Each patient will receive matching placebo once daily for 26 weeks and will then switch from placebo to 100 mg of sitagliptin once daily until Week 52. Placebo and sitagliptin will be given with protocol-specified doses of metformin immediate release.

Treatment:

Drug: Metformin immediate release

Drug: Placebo

Drug: Sitagliptin