Diabetes Mellitus, Type 2, Plasma Volume
Conditions
Keywords
Diabetes Mellitus, Type 2, Plasma Volume, Canagliflozin, Metformin, Hemoglobin A1c, Hypertension, Angiotensin-Converting Enzyme Inhibitors (ACEIs), Angiotensin Receptor Blockers (ARBs), Pharmacodynamics, Pharmacokinetics
Brief summary
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
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.
Interventions
DRUGCanagliflozin
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)
DRUGPlacebo
Form = capsules, route = oral use. One capsule once daily for up to approximately 85 days (approximately 12 weeks)
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
25 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in hematology laboratory analytes | Baseline up to Day 98 | Baseline is defined as up to 3 days predose (Week -1) |
| Change in electrocardiogram (ECG) parameters | Baseline up to Day 98 | Baseline is defined as up to 3 days predose (Week -1) |
| Change in blood pressure measurements | Baseline up to Day 98 | Baseline is defined as up to 3 days predose (Week -1) |
| Number of patients with physical examination findings reported as adverse events | Baseline up to Week 12 | Baseline is defined as up to 3 days predose (Week -1) |
| Change from baseline in pulse rate (beats/minute) | Baseline up to Day 98 | Baseline is defined as up to 3 days predose (Week -1) |
| Change in chemistry laboratory analytes | Baseline up to Day 98 | Baseline is defined as up to 3 days predose (Week -1) |
| Change from baseline in urinalysis laboratory analytes | Baseline up to Day 98 | Baseline is defined as up to 3 days predose (Week -1) |
| Change in plasma volume (PV) | Baseline to Week 12 of the double-blind treatment period | 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 | Day 1 to Day 85 | Treatment-related adverse events are adverse events with onset during the treatment phase. |
| Number of hypoglycemic events reported | Baseline up to Day 98 | Baseline is defined as up to 3 days predose (Week -1) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in PV | Baseline to Week 1 of the double-blind treatment period | Baseline is defined as up to 3 days predose (Week -1) |
| Change in body weight | Baseline to approximately Week 1 and Week 12 of Double-Blind Treatment Phase | Baseline is defined as up to 3 days predose (Week -1) |
| Change in 24-hour urine volume | Baseline to approximately Week 1 and Week 12 of Double-Blind Treatment Phase | Baseline is defined as up to 3 days predose (Week -1) |
| Change in urine pH | Baseline to approximately Week 1 and Week 12 of Double-Blind Treatment Phase | Baseline is defined as up to 3 days predose (Week -1) |
| Change in percent Hemoglobin A1c (HbA1c) | Baseline to Week 12 | Baseline is defined as up to 3 days predose (Week -1) |
| Change in 24-hour fractional and total excretion of uric acid | Baseline to approximately Week 1 and Week 12 of Double-Blind Treatment Phase | Baseline is defined as up to 3 days predose (Week -1) |
Countries
Germany
Outcome results
None listed