Evaluation of Blood Pressure Reduction, Safety, and Tolerability of Canagliflozin in Patients With Hypertension and Type 2 Diabetes Mellitus on Stable Doses of Anti-hyperglycemic and Anti-hypertensive Agents

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Evaluate the Blood Pressure Reduction With Ambulatory Blood Pressure Monitoring (ABPM), Safety, and Tolerability of Canagliflozin in the Treatment of Subjects With Hypertension and Type 2 Diabetes Mellitus

The purpose of this study is to evaluate the effect of canagliflozin (JNJ-28431754) on blood pressure reduction, compared to placebo, in patients with hypertension and type 2 diabetes mellitus and who are on stable doses of anti-hyperglycemic and anti-hypertensive agents. Overall safety and tolerability of canagliflozin will be assessed.

This is a randomized (study drug assigned by chance), double blind (neither the patient nor the study doctor will know the name of the assigned treatment), parallel-group, 3-arm (patients will be assigned to 1 of 3 treatment groups) multicenter study to determine the effect of canagliflozin (100 mg and 300 mg) on blood pressure (BP) reduction compared to placebo (a pill that looks like all the other treatments but has no real medicine) in patients with hypertension and type 2 diabetes mellitus (T2DM). The study will consist of 3 phases: a screening phase, a double-blind treatment phase and a follow-up period. Approximately 153 participants will be randomly assigned to 1 of 3 treatment groups (in a 1:1:1 ratio) in the double-blind treatment phase to receive canagliflozin 100 mg, canagliflozin 300 mg or placebo for 6 weeks. The total duration of participation in this study will be approximately 13 weeks.

Inclusion Criteria:

• patients with a diagnosis of type 2 diabetes mellitus
• patients with hypertension (seated office SBP of >=130 mmHg and <160 mmHg and seated office DBP of >= 70 mmHg at screening and at Week -2
• patients on stable doses of 1 to 3 anti-hypertensive agents for at least 5 weeks before screening
• patients on stable doses of 1 to 3 oral anti-hyperglycemic agents which must include metformin, for at least 8 weeks before screening

Exclusion Criteria:

• a history of diabetic ketoacidosis
• type 1 diabetes mellitus (T1DM)
• pancreas or beta-cell transplantation
• fasting C-peptide <0.70 ng/mL (0.23 nmol/L)
• body mass index <30 kg/m2
• has ongoing, inadequately controlled thyroid disorder
• has a history of cardio-renal disease that required treatment with immunosuppressive therapy.