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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Hypertension, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Canagliflozin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Canagliflozin 100 mg<br>Each patient will receive 100 mg of canagliflozin once daily for 6 weeks. | Drug: Canagliflozin<br>* One 100 mg or 300 mg over-encapsulated tablet orally (by mouth) in addition to the patient's anti-hyperglycemic agents (AHA) regimen used in accordance with local prescribing information.<br>|
| Experimental: Canagliflozin 300 mg<br>Each patient will receive 300 mg of canagliflozin once daily for 6 weeks. | Drug: Canagliflozin<br>* One 100 mg or 300 mg over-encapsulated tablet orally (by mouth) in addition to the patient's anti-hyperglycemic agents (AHA) regimen used in accordance with local prescribing information.<br>|
| Placebo Comparator: Placebo<br>Each patient will receive matching placebo once daily for 6 weeks. | Drug: Placebo<br>* One matching placebo capsule orally in addition to the patient's anti-hyperglycemic agents (AHA) regimen used in accordance with local prescribing information.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Mean 24-Hour Systolic Blood Pressure (SBP) to Week 6 | The blood pressure (BP) was evaluated by Ambulatory Blood Pressure Monitoring (ABPM) for all participants based on the 24-hour BP recordings. | Baseline and Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean 24-Hour Systolic Blood Pressure (SBP) to Day 2 | The blood pressure (BP) was evaluated by Ambulatory Blood Pressure Monitoring (ABPM) for all participants based on the 24-hour BP recordings. | Baseline and Day 2 | 
| Change From Baseline in the Mean 24-Hour Diastolic Blood Pressure (DBP) to Day 2 and to Week 6 | The blood pressure (BP) was evaluated by Ambulatory Blood Pressure Monitoring (ABPM) for all participants based on the 24-hour BP recordings. | Baseline, Day 2 and Week 6 | 
| Change From Baseline in Mean Daytime Systolic Blood Pressure (SBP) to Day 2 and to Week 6 | The diurnal rise (daytime) in blood pressure (BP) was evaluated by Ambulatory Blood Pressure Monitoring (ABPM) for all participants based on the 24-hour BP recordings. | Baseline, Day 2 and Week 6 | 
| Change From Baseline in Mean Daytime Diastolic Blood Pressure (DBP) to Day 2 and to Week 6 | The diurnal rise (daytime) in blood pressure (BP) was evaluated by Ambulatory Blood Pressure Monitoring (ABPM) for all participants based on the 24-hour BP recordings. | Baseline, Day 2 and Week 6 | 
| Change From Baseline in Mean Nighttime Systolic Blood Pressure (SBP) to Day 2 and to Week 6 | The nocturnal fall (nighttime) in blood pressure (BP) was evaluated by Ambulatory Blood Pressure Monitoring (ABPM) for all participants based on the 24-hour BP recordings. | Baseline, Day 2 and Week 6 | 
| Change From Baseline in Mean Nighttime Diastolic Blood Pressure (DBP) to Day 2 and to Week 6 | The nocturnal fall (nighttime) in blood pressure (BP) was evaluated by Ambulatory Blood Pressure Monitoring (ABPM) for all participants based on the 24-hour BP recordings. | Baseline, Day 2 and Week 6 | 
| Change From Baseline in Fasting Plasma Glucose (FPG) to Week 6 | The fasting plasma glucose was evaluated. | Baseline and Week 6 | 
| Change From Baseline in Body Weight to Week 6 | Body weight was evaluated. | Baseline and Week 6 | 
| Change From Baseline in Seated Office Blood Pressure (BP) to Day 2, to Week 3, and to Week 6 | The seated office blood pressure (BP) was evaluated for all participants based on the 24-hour BP recordings. SBP=Systolic Blood Pressure and DBP=Diastolic Blood Pressure. | Baseline, Day 2, Week 3 and 6 | 
| Change From Baseline in Standing Office Blood Pressure (BP) to Day 2, to Week 3, and to Week 6 | The standing office blood pressure (BP) was evaluated for all participants based on the 24-hour BP recordings. SBP=Systolic Blood Pressure and DBP=Diastolic Blood Pressure. | Baseline, Day 2, Week 3 and 6 | 
| Change From Baseline in Seated Heart Rate (HR) to Day 2, to Week 3, and to Week 6 | The seated heart rate was evaluated. | Baseline, Day 2, Week 3 and 6 | 
| Change From Baseline in Standing Heart Rate (HR) to Day 2, to Week 3, and to Week 6 | The standing heart rate was evaluated. | Baseline, Day 2, Week 3 and 6 | 
| Change From Baseline in the Difference in Seated Office Blood Pressure (BP) and Standing Office BP to Day 2, to Week 3, and to Week 6 | The difference in seated office blood pressure and standing office blood pressure was evaluated. | Baseline, Day 2, Week 3 and 6 | 
| Change From Baseline in the Difference in Seated Heart Rate (HR) and Standing HR to Day 2, to Week 3, and to Week 6 | The difference in seated heart rate and standing heart rate was evaluated. | Baseline, Day 2, Week 3 and 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension, Diabetes Mellitus, Type 2, Canagliflozin, JNJ 28431754, Sodium-Glucose Transporter 2, Blood Glucose, Type 2 Diabetes Mellitus