Safety and Efficacy of AT-001 in Patients With Diabetic Cardiomyopathy

Applied Therapeutics

Status and phase: Active, not recruiting; Phase 3

Conditions: Diabetic Cardiomyopathies

Treatments: Drug: AT-001; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04083339

AT-001-2001

Details and patient eligibility

About

This is a multicenter, randomized, placebo-controlled, 2-part study to evaluate the safety and efficacy of AT-001 in adult patients (N=675) with Diabetic Cardiomyopathy at high risk of progression to overt heart failure.

Full description

The study consists of two consecutive parts: Part A and Part B. Part A will evaluate the safety and efficacy of two doses of AT-001 vs placebo. The primary objective of Part A is to demonstrate that AT-001 improves or prevents the decline of functional capacity in patients with Diabetic Cardiomyopathy. Part B is an extension of at least 12 months that will evaluate the safety and efficacy of chronic administration of AT-001 vs placebo in the same patients who had previously been evaluated in Part A. Assessments in Part B will include safety endpoints and exploratory clinical efficacy endpoints, i.e. death and hospitalization due to a cardiac event.

Enrollment: 675 estimated patients

Sex: All

Ages: 40+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Type 2 Diabetes Mellitus
• Diabetic cardiomyopathy
• Peak VO2 < 75% of predicted normal value based on age and gender

Exclusion criteria

• Prior diagnosis or signs/symptoms of overt/symptomatic heart failure / stage C heart failure
• Prior echocardiogrphic measurement of ejection fraction (EF) < 40%
• Prior acute coronary syndrome (ACS), coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), coronary artery disease (CAD) or stroke
• Severe or moderate cardiac valve disease requiring intervention
• Clinically significant arrhythmia
• Prior diagnosis of congenital, infective, toxic, infiltrative, post-partum, or hypertrophic cardiomyopathy
• Blood pressure > 140 mmHg (systolic) or > 90 mmHg (diastolic) at screening
• HbA1c >8.5% at screening
• Severe disease that would impact the performance of a cardio-pulmonary exercise test

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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675 participants in 3 patient groups, including a placebo group

AT-001 High dose

Experimental group

Description:

The total daily doses will be of 3g. The dose selection and the frequency of dosing was based on the results of the phase 1/2 study demonstrating that 3g/day of AT-001 is capable of producing the maximum inhibition of the production of sorbitol (a pharmacodynamic biomarker of biological activity).

Treatment:

Drug: AT-001

AT-001 Low Dose

Experimental group

Description:

The total daily doses will be of 2g. The dose selection and the frequency of dosing was based on the results of the phase 1/2 study demonstrating that 2g/day of AT-001 is capable of producing a sufficient inhibition of the production of sorbitol (a pharmacodynamic biomarker of biological activity).

Treatment:

Drug: AT-001

Placebo Comparator

Placebo Comparator group

Description:

Placebo capsules will be used as comparator

Treatment:

Drug: Placebo