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

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the effects of canagliflozin on plasma volume and renal parameters in patients with Type 2 Diabetes Mellitus who are currently taking metformin and being treated for high blood pressure.

Detailed Description
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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.

Official Title
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A Double-Blind, Placebo-Controlled, Randomized, Parallel-Groups Study to Investigate the Effects of JNJ-28431754 (Canagliflozin) on Plasma Volume and Renal Function in Subjects With Type 2 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 2, Plasma Volume

Intervention / Treatment
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* Drug: Canagliflozin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients must have a diagnosis of T2DM with inadequate glycemic control (ie, HbA1c of >=7.0% and <=9.0% at Screening) on metformin monotherapy and be receiving therapy with an antihypertensive agent (an ACEI or ARB) for at least 4 weeks prior to Screening Exclusion Criteria: -History of diabetic ketoacidosis, type 1 diabetes mellitus (T1DM), pancreas or beta cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy; or a severe hypoglycemic episode within 6 months before screening

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 70 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<br> | Drug: Canagliflozin<br>* Type = exact number, unit = mg, number = 300, form = capsule, route = oral use. One encapsulated tablet once daily for up to approximately 85 days (approximately 12 weeks)<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Form = capsules, route = oral use. One capsule once daily for up to approximately 85 days (approximately 12 weeks)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in plasma volume (PV) | Baseline is defined as up to 3 days predose (Week -1) | Baseline to Week 12 of the double-blind treatment period | 
| Number of patients who experience at least 1 occurrence of a treatment-related adverse event | Treatment-related adverse events are adverse events with onset during the treatment phase. | Day 1 to Day 85 | 
| Number of hypoglycemic events reported | Baseline is defined as up to 3 days predose (Week -1) | Baseline up to Day 98 | 
| Change in electrocardiogram (ECG) parameters | Baseline is defined as up to 3 days predose (Week -1) | Baseline up to Day 98 | 
| Change in blood pressure measurements | Baseline is defined as up to 3 days predose (Week -1) | Baseline up to Day 98 | 
| Number of patients with physical examination findings reported as adverse events | Baseline is defined as up to 3 days predose (Week -1) | Baseline up to Week 12 | 
| Change from baseline in pulse rate (beats/minute) | Baseline is defined as up to 3 days predose (Week -1) | Baseline up to Day 98 | 
| Change in chemistry laboratory analytes | Baseline is defined as up to 3 days predose (Week -1) | Baseline up to Day 98 | 
| Change from baseline in urinalysis laboratory analytes | Baseline is defined as up to 3 days predose (Week -1) | Baseline up to Day 98 | 
| Change in hematology laboratory analytes | Baseline is defined as up to 3 days predose (Week -1) | Baseline up to Day 98 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in PV | Baseline is defined as up to 3 days predose (Week -1) | Baseline to Week 1 of the double-blind treatment period | 
| Change in body weight | Baseline is defined as up to 3 days predose (Week -1) | Baseline to approximately Week 1 and Week 12 of Double-Blind Treatment Phase | 
| Change in 24-hour urine volume | Baseline is defined as up to 3 days predose (Week -1) | Baseline to approximately Week 1 and Week 12 of Double-Blind Treatment Phase | 
| Change in 24-hour fractional and total excretion of uric acid | Baseline is defined as up to 3 days predose (Week -1) | Baseline to approximately Week 1 and Week 12 of Double-Blind Treatment Phase | 
| Change in urine pH | Baseline is defined as up to 3 days predose (Week -1) | Baseline to approximately Week 1 and Week 12 of Double-Blind Treatment Phase | 
| Change in percent Hemoglobin A1c (HbA1c) | Baseline is defined as up to 3 days predose (Week -1) | Baseline to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus, Type 2, Plasma Volume, Canagliflozin, Metformin, Hemoglobin A1c, Hypertension, Angiotensin-Converting Enzyme Inhibitors (ACEIs), Angiotensin Receptor Blockers (ARBs), Pharmacodynamics, Pharmacokinetics