A Study to Evaluate the Effectiveness, Safety, and Tolerability of Canagliflozin in Combination With Metformin in the Treatment of Patients With Type 2 Diabetes Mellitus With Inadequate Glycemic Control With Diet and Exercise

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 3

Conditions: Diabetes Mellitus, Type 2

Treatments: Drug: Canagliflozin 100 mg; Drug: Canagliflozin 300 mg; Drug: Metformin XR

Study type: Interventional

Funder types: Industry

Identifiers

NCT01809327

2011-000400-17 (EudraCT Number)

CR100034

28431754DIA3011 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to assess the effectiveness of the co-administration of canagliflozin and metformin extended release (XR) compared with canagliflozin alone, and metformin XR alone in patients with type 2 diabetes mellitus with inadequate control despite treatment with diet and exercise. The safety and tolerability of canagliflozin will also be assessed.

Full description

This study will be a randomized (the study medication is assigned by chance), double-blind (neither physician nor participant knows the identity of the assigned treatment), active-controlled (one of the treatments is an established effective treatment for type 2 diabetes mellitus), parallel-group (each group of participants will be treated at the same time), 5-arm (groups), multicenter study. Approximately 1,200 participants will be randomly assigned to the 5 treatment arms in a 1:1:1:1:1 ratio for 26 weeks.

Enrollment: 1,186 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Must have type 2 diabetes mellitus with inadequate glycemic control on diet and exercise
• Not on antihyperglycemic agent therapy (at least 12 weeks before screening) and have a screening visit fingerstick glycated hemoglobin (HbA1c) of more than or equal to 7 percent and less than or equal to 12.5 percent
• Have a screening visit HbA1c of more than or equal to 7.5 percent and less than or equal to 12 percent as determined by the central laboratory
• Must have a fasting plasma glucose of less than or equal to 300 mg/dL (16.7 mmol/L) prior to randomization
• Must have a fasting fingerstick glucose of greater than 120 mg/dL (6.7 mmol/L) performed at home or at the study center prior to randomization

Exclusion criteria

• History of diabetic ketoacidosis, type 1 diabetes mellitus (T1DM), pancreas or beta-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy
• Fasting C-peptide less than 0.70 ng/mL (0.23 nmol/L) in participants for whom the investigator cannot reasonably exclude T1DM based upon clinical evaluation
• Repeated (2 or more over a 1 week period) fasting self-monitored blood glucose measurements more than 300 mg/dL (16.7 mmol/L) prior to randomization, despite reinforcement of diet and exercise counseling
• History of hereditary glucose-galactose malabsorption or primary renal glucosuria
• Has history of, or currently active, illness considered to be clinically significant by the Investigator or any other illness that the Investigator considers should exclude the patient from the study or that could interfere with the interpretation of the study results

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

1,186 participants in 5 patient groups

Canagliflozin 100 mg

Experimental group

Description:

Participants will receive one 100 mg canagliflozin capsule before the morning meal and one matching placebo capsule with the evening meal plus placebo tablets with the evening meal (to match the metformin XR tablets administered in other treatment arms) for 26 weeks.

Treatment:

Drug: Canagliflozin 100 mg

Canagliflozin 300 mg

Experimental group

Description:

Participants will receive one 300 mg canagliflozin capsule before the morning meal and one matching placebo capsule with the evening meal plus placebo tablets with the evening meal (to match the metformin XR tablets administered in other treatment arms) for 26 weeks.

Treatment:

Drug: Canagliflozin 300 mg

Metformin XR

Experimental group

Description:

Participants will receive metformin XR tablets (in doses titrated over 9 weeks) once daily with the evening meal, plus one placebo capsule before the morning meal and one placebo capsule with the evening meal (to match the canagliflozin capsules administered in other treatment arms) for 26 weeks.

Treatment:

Drug: Metformin XR

Canagliflozin 100 mg + Metformin XR

Experimental group

Description:

Participants will receive one 100 mg canagliflozin capsule with the evening meal and one matching placebo capsule before the morning meal plus metformin XR tablets (in doses titrated over 9 weeks) once daily with the evening meal for 26 weeks.

Treatment:

Drug: Canagliflozin 100 mg

Drug: Metformin XR

Canagliflozin 300 mg + Metformin XR

Experimental group

Description:

Participants will receive one 300 mg canagliflozin capsule with the evening meal and one matching placebo capsule before the morning meal plus metformin XR tablets (in doses titrated over 9 weeks) once daily with the evening meal for 26 weeks.

Treatment:

Drug: Canagliflozin 300 mg

Drug: Metformin XR