Diabetic Cardiomyopathy (DbCM) / Stage B Heart Failure (SBHF) MedDRA version: 20.0 Level: PT Classification code 10012647 Term: Diabetic cardiomyopathy System Organ Class: 10007541 - Cardiac disorders
Conditions
Interventions
Product Name: AT-001
Product Code: AT-001
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Not Available
CAS Number: Not Assigned
Current Sponsor code: AT-001
Other descriptive name: AT-001
Co
Sponsors
Applied Therapeutics Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Type 2 Diabetes Mellitus (T2DM) 2. One of the following age-related criteria: Age = 60 years OR • Age = 40 years to = 45% AND • At least 1 of the following 5 abnormalities: o Absolute value of Global longitudinal strain (GLS) -16%) o Left ventricular hypertrophy (LVH) defined as left ventricular mass index (LVMI) = 95 g/m2 in women and = 115 g/m2 in men o Left atrial enlargement (LAE) defined as left atrial volume index (LAVi) = 34 mL/m2 o Diastolic Dysfunction defined as E/E’ = 13 o Right ventricular systolic pressure (RVSP) > 35 mmHg 4. CPET demonstration of both, as confirmed by the CPET core lab: • Impaired functional capacity, i.e., Peak VO2 =65 years) yes F.1.3.1 Number of subjects for this age range 405
Exclusion criteria
Exclusion criteria: 1.Prior diagnosis of overt/symptomatic heart failure / stage C heart failure, including any prior or current symptom or sign that led to a diagnosis of overt/symptomatic heart failure / stage C heart failure. 2. Any prior echocardiographic measurement indicating ejection fraction (EF) 140 mmHg (systolic) or > 90 mmHg (diastolic) at screening 13. History of hospitalization for hypertensive emergency 14. BMI > 40 kg/m2 15. Antihyperglycemic treatment has not been stable in the 12 weeks prior to screening in the opinion of the Investigator 16. Treatment with inhibitors of the renin-angiotensin-aldosterone system (RAAS) has not been stable in the 12 weeks prior to screening in the opinion of the Investigator 17. Use of thiazolidinediones at screening and/or after randomization 18. Planned start of a SGLT2-inhibitor during the study 19. Any current or prior use of a loop diuretic 20. Pregnant or breastfeeding women 21. Females of childbearing potential not willing to use a highly effective form of birth control from screening until the Study Closeout Visit, or Post-Treatment Follow-up Visit, whichever occurs later 22. Severe disease or short life expectancy (<12 months) making implementation of the protocol or interpretation of the study results difficult (This includes clinically significant hematopoietic, renal, hepatic (including hepatitis B and C), endocrine, pulmonary, neurological, psychiatric, immunological (including HIV-AIDS), dermatological, or gastrointestinal diseases or active malignant tumor [except for non-melanoma skin cancer] or conditions capable of altering the absorption, metabolism, or elimination of drugs, or conditions that would impact the performance of a CPET [e.g., chronic lung or neuro-muscular disease].) 23. Morbid obesity or any other condition that prevents the obtainment of a good quality echocardiogram at baseline 24. History of substance abuse (including alcohol) 25. History of clinically significant drug allergy or drug hypersensitivity reactions 26. Severe lower extremity complications (such as skin ulcers, osteomyelitis and gangrene) and/or history of non-traumatic amputations 27. Prior diagnosis of proliferative diabetic retinopathy 28. Investigators, site personnel directly affiliated with this study, and their immediate families (Immediate family is defined as a spouse, parent, child, or sibling, whethe
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate that AT-001 compared with placebo decreases the worsening of performance on a cardiopulmonary exercise test (CPET) in patients with Diabetic Cardiomyopathy (DbCM) / Stage B Heart Failure (SBHF) ;Secondary Objective: To evaluate • the efficacy of AT-001 compared with placebo in preventing progression from SBHF to Stage C Heart Failure • the effect of AT-001 compared with placebo in patients with DbCM/SBHF on the levels of NT-proBNP • the effect of AT-001 compared with placebo in patients with DbCM/SBHF on the score of the mKCCQ • the effect of AT-001 compared with placebo in patients with DbCM/SBHF on the percentage of patients with any changes and clinically significant changes (>6%) in peak oxygen uptake • the effect of AT-001 compared with placebo in patients with DbCM/SBHF on the significant worsening of DbCM from baseline • the effect of AT-001 compared with placebo in patients with DbCM/SBHF on the changes in global longitudinal strain, left ventricular hypertrophy, left atrial enlargement, diastolic dysfunction, and right ventricular systolic pressure by echocardiography • the safety of chronic administration of AT-001 to patients with DbCM/SBHF;Primary end point(s): Changes in CPET performance (peak oxygen uptake [peak VO2]) from baseline to Month 15 (>=15 months and = 18 months after randomization) and possibly to Month 27 (>= 27 months and = 30 months after randomization);Timepoint(s) of evaluation of this end point: Baseline to Month 15 (>=15 months and = 18 months after randomization) and possibly to Month 27 (>= 27 months and = 30 months after randomization) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Changes in NT-proBNP from baseline to Month 15 • Progression to SCHF, defined by the occurrence of at least 1 of the following events by Month 27: o CV death o Hospitalization for HF o Urgent HF visit o New diagnosis of HF (requiring initiation of a loop diuretic) • Changes in NT-proBNP • Changes in the mKCCQ score from baseline to Month 27 • Percentage of patients with a clinically significant decrease in peak VO2 (i.e., > 6%) from baseline to Month 27 ;Timepoint(s) of evaluation of this end point: Baseline to Month 27 | — |
Countries
Australia, Canada, Czech Republic, France, Germany, Hong Kong, Poland, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trials Information
Medpace
Outcome results
None listed