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
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Canagliflozin 100 mg; Canagliflozin 300 mg; Metformin XR
Intervention description: One 100 mg capsule taken orally (by mouth) once daily either before the morning meal (for the Canagliflozin 100 mg arm) or with the evening meal (for the Canagliflozin 100 mg + Metformin XR arm).; One 300 mg capsule taken orally (by mouth) once daily either before the morning meal (for the Canagliflozin 300 mg arm) or with the evening meal (for the Canagliflozin 300 mg + Metformin XR arm).; One 500 mg tablet (Day 1 up to week 1); two 500 mg tablets (Week 1 up to Week 3); three 500 mg tablets (Week 3 to Week 6); four 500 mg tablets (Week 6 to Week 9). Tablets will be administered with the evening meal.
Intervention MeSH terms: Metformin; Canagliflozin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1186.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Diabetes Mellitus, Type 2; Diabetes Mellitus; Canagliflozin (JNJ-28431754); Metformin

Summary:

      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.
    

Eligibility criteria:

        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