Type2 Diabetes Mellitus, Cardiovascular Diseases
Conditions
Brief summary
RESEARCH HYPOTHESIS * In subjects with T2DM and HF, effect of canagliflozin will be superior to placebo for the change from baseline in PCWP after a single dose (6 hours post-dose) and after 4 weeks. * Treatment with canagliflozin will be well tolerated over 4 weeks.
Detailed description
This is a randomized, double-blind, placebo-controlled, parallel-group, single-center study (Figure 1). Thirty subjects will be randomized in a 3:2 randomization ratio to canagliflozin 300 mg once daily (QD) or placebo. The study will include a 3-week pretreatment screening phase and a 4-week double-blind treatment phase.
Interventions
Canagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor. It works by decreasing the amount of sugar the body absorbs, and increasing the amount of sugar that leaves the body in the urine. Administered in 300mg tablets.
DRUGPlacebo
Placebo for Canagliflozin
Sponsors
Janssen Scientific Affairs, LLC
The University of Texas Health Science Center at San Antonio
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Caregiver)
Intervention model description
Randomized, Double-Blind, Placebo-Controlled, Single-Center, Mechanistic Study
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* on stable doses (more than 3 months) of antihyperglycemic agents (except for an SGLT2 inhibitor and insulin) * have an A1c ≥7% and ≤11% * Estimated glomerular filtration rate (eGFR) must be ≥45 ml/min•1.73 m2 * have an NT-proBNP ≥500 pg/mL * be on a stable dose of guideline-directed HF medication (i.e., angiotensin converting enzyme \[ACE\] inhibitor, angiotensin II receptor blocker \[ARB\], or angiotensin receptor neprilysin inhibitor \[ARNI\], β-blocker, diuretics, and/or mineralcorticoid receptor antagonist) for at least 4 weeks * be on stable antihypertensive therapy for at least 2 months
Exclusion criteria
* T1DM * repeated fasting plasma glucose (FPG) or fasting self-monitored blood glucose measurements ≥240 mg/dL or both * during the pretreatment phase, NYHA Class IV HF status, uncontrolled hypertension as defined as systolic blood pressure (SBP) \>160 or diastolic blood pressure (DBP) \>100 mmHg * liver disease (ALT or AST \>3 x ULN) * anemia Hb\<10 * anticipated cardiac surgery or coronary intervention within the next 3 months * severe unremediated valvular heart disease * major CV event (e.g., MI, cerebrovascular accident) within 3 months prior to screening visit * hospitalization for HF within 2 months prior to screening visit * documented atrial fibrillation * history of atraumatic amputation within past 12 months of screening or critical ischemia of the lower extremity within 6 months of screening * an active skin ulcer, osteomyelitis, or gangrene * have an allergy to iodocyanine green and inulin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pulmonary capillary wedge pressure (PCWP) | 6 hours | The primary efficacy endpoint will be change in PCWP from baseline to end of acute administration monitoring period (6 hours). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pulmonary capillary wedge pressure (PCWP) | 4 weeks | The key secondary endpoint will be change in PCWP from baseline to 4 weeks. |
Countries
United States
Outcome results
None listed