Patients with type 2 diabetes mellitus and heart failure MedDRA version: 18.1 Level: PT Classification code 10011078 Term: Coronary artery disease System Organ Class: 10007541 - Cardiac disorders
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of informed consent prior to any study specific procedure (Pre-screening ICF and Informed Consent collected at screening) 2. Male or female, aged > o = 18 years at the time of consent 3. Documented, controlled T2DM, as defined by: -Treatment with stable doses of antidiabetic medications that have not increased or decreased for > o = 8 weeks before screening -No planned increases or reductions in antidiabetic medications during the study -With central lab HbA1c > o =7.0% and o = 7.5% and 900 pg/mL) during screening -Stable doses of HF medications (according to local standards of care), that have not increased or decreased (including diuretics, angiotensin converting enzyme [ACE] inhibitors or angiotensin receptor blocking [ARB] agents, beta blockers, and aldosterone antagonists) for > o = 8 weeks prior to screening 5. Stable HF, with no evidence of volume overload (no rales, jugular venous distention, peripheral edema) at screening 6. Normal sinus rhythm 7. Body mass index 25 to 40 kg/m2, inclusive 8. Women of childbearing potential (WOCBP): -Must be using appropriate birth control to avoid pregnancy throughout the study and for up to 4 weeks after the last dose of investigational product -Must have a negative serum or urine pregnancy test within 72 hours prior to the start of investigational product -Must not be breastfeeding Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 375 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 65
Exclusion criteria
Exclusion criteria: 1. MRI contraindications: all implanted defibrillators; implanted pacemakers and other devices/implants that in the judgment of the investigator preclude an MRI evaluation 2. Atrial fibrillation 3. Receiving incretin therapy (DPP4 inhibitors, GLP-1 mimetics), or having received incretin therapy within the previous 3 months of screening 4. Receiving therapy with an SGLT2 inhibitor or having received SGLT2 inhibitor therapy within the previous 3 months of screening 5. Receiving therapy with a TZD or having received TZD therapy within the previous 3 months of screening 6. Type 1 diabetes mellitus 7. History of unstable or rapidly progressing renal disease 8. History of unexplained microscopic or gross hematuria 9. Previously documented bladder cancer 10. Volume depletion as judged by the investigator 11. A central lab eGFR value 3X the upper limit of normal; or total bilirubin (TB) >2 mg/dL 25. History of diabetic ketoacidosis (DKA) requiring medical intervention (eg, emergency room visit and/or hospitalization) within 1 month prior to the Screening visit 26. History of malignancy within the last 5 years, excluding successful treatment of basal or squamous cell skin cancer 27. Patients who, in the judgement of the investigator, may be at risk for dehydration 28. Pregnant, positive pregnancy test, planning to become pregnant during clinical trial or breast feeding 29. History of any clinically significant disease or disorder which, in the opinion of the investigator, may put the patient at risk because of participation in the study, may influence the results, or may limit the patient's ability to participate in or complete the study 30. Unable or unwilling to provide written informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To exclude an increase in left ventricular end diastolic volume (LVEDV) index of greater than 10% (non-inferiority margin of 6.5 mL/m2) in patients with T2DM and HFtreated with saxagliptin for 24 weeks,compared to placebo.;Secondary Objective: - Evaluate the effects of saxagliptin compared to placebo on left ventricular end systolic volume (LVESV) index, left ventricular ejection fraction (LVEF), and left ventricular mass (LVM) after 24 weeks in patients with T2DM and HF - Evaluate the effects of saxagliptin compared to placebo on N-terminal prohormone of brain natriuretic peptide (NT-proBNP) after 24 weeks of treatment;Primary end point(s): Change from baseline in LVEDV index measured by Magnetic Resonance Imaging (MRI);Timepoint(s) of evaluation of this end point: 24 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Change from baseline in LVESV index, LVEF, and LVM measured by MRI - Change from baseline in NT-proBNP;Timepoint(s) of evaluation of this end point: 24 weeks | — |
Countries
Canada, Chile, Hungary, Korea, Republic of, Russian Federation, Spain, Taiwan, Thailand, United States
Contacts
Public ContactUnidad de Investigación Clínica
AstraZeneca Farmacéutica Spain, S.A.
Outcome results
None listed