Clinical trial NCT01483781: A Study of the Effects of Canagliflozin on Plasma Volume in Patients With Type 2 Diabetes Mellitus
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type 2
Plasma Volume
Keywords: Diabetes Mellitus, Type 2
Plasma Volume
Canagliflozin
Metformin
Hemoglobin A1c
Hypertension
Angiotensin-Converting Enzyme Inhibitors (ACEIs)
Angiotensin Receptor Blockers (ARBs)
Pharmacodynamics
Pharmacokinetics
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2011-12-01
Enrollment: 36
Sex: ALL
Minimum age (years): 25
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in plasma volume (PV)
timeFrame: Baseline to Week 12 of the double-blind treatment period
measure: Number of patients who experience at least 1 occurrence of a treatment-related adverse event
timeFrame: Day 1 to Day 85
measure: Number of hypoglycemic events reported
timeFrame: Baseline up to Day 98
measure: Change in electrocardiogram (ECG) parameters
timeFrame: Baseline up to Day 98
measure: Change in blood pressure measurements
timeFrame: Baseline up to Day 98
measure: Number of patients with physical examination findings reported as adverse events
timeFrame: Baseline up to Week 12
measure: Change from baseline in pulse rate (beats/minute)
timeFrame: Baseline up to Day 98
measure: Change in chemistry laboratory analytes
timeFrame: Baseline up to Day 98
measure: Change from baseline in urinalysis laboratory analytes
timeFrame: Baseline up to Day 98
measure: Change in hematology laboratory analytes
timeFrame: Baseline up to Day 98
Secondary outcomes:
measure: Change in PV
timeFrame: Baseline to Week 1 of the double-blind treatment period
measure: Change in body weight
timeFrame: Baseline to approximately Week 1 and Week 12 of Double-Blind Treatment Phase
measure: Change in 24-hour urine volume
timeFrame: Baseline to approximately Week 1 and Week 12 of Double-Blind Treatment Phase
measure: Change in 24-hour fractional and total excretion of uric acid
timeFrame: Baseline to approximately Week 1 and Week 12 of Double-Blind Treatment Phase
measure: Change in urine pH
timeFrame: Baseline to approximately Week 1 and Week 12 of Double-Blind Treatment Phase
measure: Change in percent Hemoglobin A1c (HbA1c)
timeFrame: Baseline to Week 12
Other outcomes:
Locations:
city: Neuss
country: Germany
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC L.L.C. Clinical Trial
role: STUDY_DIRECTOR
References: