A 24-Week study to investigate the effects of saxagliptin,saxagliptin combined with dapagliflozin, sitagliptin and placebo in patients with type 2 diabetes mellitus and heart failure.

• Register: EUCTR
• Last refreshed on: 29 August 2016
• Main ID: EUCTR2015-004825-14-ES
• Date of registration: 18/03/2016
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: A 24-Week study to investigate the effects of saxagliptin,saxagliptin combined with dapagliflozin, sitagliptin and placebo in patients with type 2 diabetes mellitus and heart failure.
• Scientific title: A 24-Week, Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled Study to Investigate the Effects of Saxagliptin, Saxagliptin Combined with Dapagliflozin, and Sitagliptin in Patients with Type 2 Diabetes Mellitus and Heart Failure - MEASURE-HF
• Date of first enrolment: 04/05/2016
• Target sample size: 440
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-004825-14
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Canada, Chile, Hungary, Korea, Republic of, Russian Federation, Spain, Taiwan, Thailand, United States

Contacts

• Name: Unidad de Investigación Clínica
• Affiliation: AstraZeneca Farmacéutica Spain, S.A.

• Name: Unidad de Investigación Clínica
• Affiliation: AstraZeneca Farmacéutica Spain, S.A.

Key inclusion & exclusion 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 = 9.0% value; for patients treated with sulfonylurea agents, central lab HbA1c > o = 7.5% and < o = 9.0% value; during prescreening or screening
4. HF demonstrated by all 3 of the following criteria:
-History of HF and LVEF < o = 45% within the last 6 months (echocardiogram, MRI, left ventriculography, or other accepted methodology). Patients without a recent assessment of LV function will undergo a local echocardiogram at the time of screening to determine ejection fraction
-Elevated NT-proBNP (>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:
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 <45 mL/min/1.73 m2 on pre-screening or screening
12. New York Heart Association (NYHA) Class IV HF
13. Myocardial infarction, stroke, transient ischemic attack, or coronary revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG]) within the past 6 months of screening
14. Inoperable aortic or mitral valvular heart disease. Recent (within 6 months) or planned valvular heart procedure
15. Heart failure secondary to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, and hypertrophic obstructive cardiomyopathy
16. Previous cardiac transplantation or transplantation indicated or expected within 6 months of randomization
17. Contraindications to saxagliptin therapy as outlined in the saxagliptin Investigator?s Brochure, to dapagliflozin therapy as outlined in the dapagliflozin Investigator?s Brochure, or to sitagliptin therapy as outlined in the sitagliptin prescribing information
18. Current treatment with strong cytochrome P450 (CYP) 3A4/5 inhibitors
19. Involvement in the planning and/or conduct of the study (applies to both AZ staff and/or staff at the study site)
20. Previous enrollment or randomization in the present study
21. Participation in another clinical study with an investigational product during the last 30 days
22. Patients either employed by or immediate relatives of the Sponsor
23. Known human immunodeficiency virus (HIV) infection
24. Severe hepatic disease, including chronic active hepatitis. Positive serologic evidence of current infectious liver disease, including patients who are known to be positive for hepatitis B viral antibody IgM, hepatitis B surface antigen, or hepatitis C virus antibody; or aspartate transaminase (AST) or alanine transaminase (ALT)>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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

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

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Intervention(s)

Trade Name: Forxiga
Product Name: Dapagliflozin
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: DAPAGLIFLOZIN PROPANEDIOL
CAS Number: 960404-48-2
Other descriptive name: DAPAGLIFLOZIN PROPANEDIOL MONOHYDRATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Onglyza
Product Name: Saxagliptin
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: SAXAGLIPTIN
CAS Number: 361442-04-8
Other descriptive name: SAXAGLIPTIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Onglyza
Product Name: Saxagliptin
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: SAXAGLIPTIN
CAS Number: 361442-04-8
Other descriptive name: SAXAGLIPTIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Januvia
Product Name: Sitagliptin
Pharmaceutical Form: Capsule
INN or Proposed INN: Sitagliptin phosphate
CAS Number: 654671-77-9
Other descriptive name: Sitagliptin phosphate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Trade Name: Januvia
Product Name: Sitagliptin
Pharmaceutical Form: Capsule
INN or Proposed INN: Sitagliptin phosphate
CAS Number: 654671-77-9
Other descriptive name: Sitagliptin phosphate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

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

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.

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 Outcome(s)

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

Secondary ID(s)

D1680C00016

Source(s) of Monetary Support

AstraZeneca AB