A Study of the Effects of Canagliflozin on Plasma Volume in Patients With Type 2 Diabetes Mellitus

• Change in plasma volume (PV) [ Time Frame: Baseline to Week 12 of the double-blind treatment period ] [ Designated as safety issue: No ]
  Baseline is defined as up to 3 days predose (Week -1)
  
  
• Number of patients who experience at least 1 occurrence of a treatment-related adverse event [ Time Frame: Day 1 to Day 85 ] [ Designated as safety issue: No ]
  Treatment-related adverse events are adverse events with onset during the treatment phase.
  
  
• Number of hypoglycemic events reported [ Time Frame: Baseline up to Day 98 ] [ Designated as safety issue: No ]
  Baseline is defined as up to 3 days predose (Week -1)
  
  
• Change in electrocardiogram (ECG) parameters [ Time Frame: Baseline up to Day 98 ] [ Designated as safety issue: No ]
  Baseline is defined as up to 3 days predose (Week -1)
  
  
• Change in blood pressure measurements [ Time Frame: Baseline up to Day 98 ] [ Designated as safety issue: No ]
  Baseline is defined as up to 3 days predose (Week -1)
  
  
• Number of patients with physical examination findings reported as adverse events [ Time Frame: Baseline up to Week 12 ] [ Designated as safety issue: No ]
  Baseline is defined as up to 3 days predose (Week -1)
  
  
• Change from baseline in pulse rate (beats/minute) [ Time Frame: Baseline up to Day 98 ] [ Designated as safety issue: No ]
  Baseline is defined as up to 3 days predose (Week -1)
  
  
• Change in chemistry laboratory analytes [ Time Frame: Baseline up to Day 98 ] [ Designated as safety issue: No ]
  Baseline is defined as up to 3 days predose (Week -1)
  
  
• Change from baseline in urinalysis laboratory analytes [ Time Frame: Baseline up to Day 98 ] [ Designated as safety issue: No ]
  Baseline is defined as up to 3 days predose (Week -1)
  
  
• Change in hematology laboratory analytes [ Time Frame: Baseline up to Day 98 ] [ Designated as safety issue: No ]
  Baseline is defined as up to 3 days predose (Week -1)
  
  

• Change in PV [ Time Frame: Baseline to Week 1 of the double-blind treatment period ] [ Designated as safety issue: No ]
  Baseline is defined as up to 3 days predose (Week -1)
  
  
• Change in body weight [ Time Frame: Baseline to approximately Week 1 and Week 12 of Double-Blind Treatment Phase ] [ Designated as safety issue: No ]
  Baseline is defined as up to 3 days predose (Week -1)
  
  
• Change in 24-hour urine volume [ Time Frame: Baseline to approximately Week 1 and Week 12 of Double-Blind Treatment Phase ] [ Designated as safety issue: No ]
  Baseline is defined as up to 3 days predose (Week -1)
  
  
• Change in 24-hour fractional and total excretion of uric acid [ Time Frame: Baseline to approximately Week 1 and Week 12 of Double-Blind Treatment Phase ] [ Designated as safety issue: No ]
  Baseline is defined as up to 3 days predose (Week -1)
  
  
• Change in urine pH [ Time Frame: Baseline to approximately Week 1 and Week 12 of Double-Blind Treatment Phase ] [ Designated as safety issue: No ]
  Baseline is defined as up to 3 days predose (Week -1)
  
  
• Change in percent Hemoglobin A1c (HbA1c) [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
  Baseline is defined as up to 3 days predose (Week -1)
  
  

This is a double-blind (neither the patient or study staff will know the identity of the treatment assigned) in patients with Type 2 Diabetes Mellitus (T2DM) who have inadequate glycemic (blood sugar) control on metformin monotherapy (metformin taken alone for control of T2DM) and who are currently being treated for hypertension (high blood pressure) with agents called angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs). In the study, patients will be randomized (assigned by chance) to receive treatment with canagliflozin or a placebo (a treatment identical in appearance to canagliflozin but does not contain active drug) for 12 weeks. During the 12-week treatment period, patients will also take metformin at a dose of at least 1500 mg/day in addition to their prescribed ACEI or ARB for hypertension. Patients will participate in the study for up to approximately 22 weeks.