Effect of Ertugliflozin on Cardiac Function in Diabetes

Study Overview
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Brief Summary
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The aim of this study is to investigate the beneficial role of ertugliflozin, a new SGLT2 inhibitor, in cardiac function via measuring GLS as well as other hemodynamic factors using echocardiogram in patients with T2D and HF, who are not controlled with oral antidiabetic medications including DPP4 inhibitors.

Detailed Description
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This study is a phase 3, randomized, double-blind, active-competitor, parallel-group study that is anticipated to enroll 120 patients. Patients taking metformin and/or DPP4 inhibitors as per local label for ≥12 weeks without a dose adjustment before enrollment will be eligible for screening. All patients will have a screening period comprised of an up to 2-week screening phase prior to randomization. In order to qualify for randomization, patients must demonstrate compliance based upon pill count (80%) and discretion of the investigators during the Run-in phase. Glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) will be masked to patients after randomization. To prevent partial unblinding, urinary glucose excretion (UGE) results will be masked to patients. Urine glucose, albumin, calcium, and creatinine will be measured separately on-site visits.

Official Title
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A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group, to Evaluate the Effect of Ertugliflozin on Cardiac Function in Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control and Stage B Heart Failure

Conditions
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Type2 Diabetes, Heart Failure

Intervention / Treatment
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* Drug: Ertugliflozin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with T2D taking oral antidiabetic medications (metformin and/or DPP4 inhibitors) except SGLT2 inhibitors for at least 12 weeks without a dose adjustment before enrollment. eGFR ≥ 45 mL/min/1.73 m2. Stage B HF identified on the basis of either structural or functional markers. Exclusion Criteria: Type 1 diabetes mellitus At the time of screening age <20 years HbA1c <7% or HbA1c >9.5% at Screening FPG >15 mmol/L (270 mg/dL) measured by the laboratory at Screening (Visit 1), and confirmed (>15 mmol/L [>270 mg/dL]) by a repeat test before randomization Treated with insulin and/or GLP-1R agonist within 12 weeks preceding the Screening Visit. Women of childbearing potential with no effective contraceptive method History of gastric surgery including history of gastric banding within 3 years before the Screening Visit History of diabetic ketoacidosis or nonketotic hyperosmolar coma prior to the Screening Visit Mean blood pressure after 3 separate measurements >180 mmHg in systolic blood pressure (SBP) or >95 mmHg in diastolic blood pressure (DBP) Patients with current or prior symptoms of HF. Patients with severe anemia, severe respiratory, hepatic, neurological, psychiatric disorders or active malignant tumor or other major systemic disease or patients with short life expectancy making implementation of the protocol or interpretation of the study results difficult Aspartate aminotransferase and/or alanine aminotransferase: >3 times the upper limit of the normal laboratory range (ULN) Total bilirubin: >1.5 times ULN (except in case of Gilbert's syndrome) Use of systemic glucocorticoids (excluding topical or ophthalmic, application or inhaled forms) for more than 10 consecutive days within 90 days prior to the Screening Visit Patient who has taken other investigational drugs or prohibited therapy for this study within 3 months

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ertugliflozin<br>Ertugliflozin 5 mg in addition to their preexisting metformin and/or DPP4 inhibitor | Drug: Ertugliflozin<br>* Ertugliflozin as add-on to Metformin and/or DPP4 inhibitors in patients with inadequately controlled type 2 diabetes<br>* Other names: Steglatro;|
| Placebo Comparator: Control group<br>Placebo in addition to their preexisting metformin and/or DPP4 inhibitor | Drug: Placebo<br>* Placebo as add-on to Metformin and/or DPP4 inhibitors in patients with inadequately controlled type 2 diabetes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global Longitudinal Strain (GLS) | Change of GLS after 24 weeks' treatment | Baseline, week 12, week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| E/e' ratio | Change of E/e' after 24 weeks' treatment | Baseline, week 12, week 24 | 
| Ejection fraction (EF) | Change of EF after 24 weeks' treatment | Baseline, week 12, week 24 | 
| Left ventricle mass | Change of LV mass after 24 weeks' treatment | Baseline, week 12, week 24 | 
| Glycated hemoglobin | Change of HbA1c mass after 24 weeks' treatment | Baseline, week 12, week 24 | 
| Body weight | Change of body weight mass after 24 weeks' treatment | Baseline, week 12, week 24 | 
| Body Fat Mass | Change of body fat mass after 24 weeks' treatment | Baseline, week 12, week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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type 2 diabetes, heart failure, ertugliflozin, Global longitudinal strain (GLS)