What side effects are associated with this type of intervention?

Common treatments for cardiomyopathy include Aldose Reductase Inhibitors (ARIs), beta-blockers, ACE inhibitors, and SGLT2 inhibitors. ARIs, like AT-001, are being studied for their efficacy and safety, with potential side effects including gastrointestinal distress and elevated liver enzymes. Beta-blockers can cause fatigue, cold extremities, and bradycardia. ACE inhibitors may lead to cough, hyperkalemia, and renal impairment. SGLT2 inhibitors, such as empagliflozin, are generally well-tolerated but can cause urinary tract infections, genital infections, and dehydration.

What prior FDA approvals exist?

The FDA has approved several treatments for cardiomyopathy, focusing on managing symptoms and slowing disease progression. While specific information on aldose reductase inhibitors like AT-001 is not provided, other treatments include MR antagonists like eplerenone, which has shown efficacy in reducing inflammatory foci in hypertensive rat hearts. Additionally, SGLT2 inhibitors, such as empagliflozin, have demonstrated benefits in reducing cardiovascular events in patients with chronic kidney disease, which can overlap with cardiomyopathy management. These treatments aim to provide cardiac protection and improve patient outcomes.

What other types of research exist?

Promising novel alternatives to AT-001 for cardiomyopathy patients include SGLT2 inhibitors like dapagliflozin and empagliflozin, which have shown benefits in heart failure patients with and without diabetes. Additionally, GLP-1 receptor agonists such as semaglutide and liraglutide have demonstrated cardiovascular benefits in diabetic patients. Another potential alternative is omecamtiv mecarbil, a cardiac myosin activator that has shown efficacy in systolic heart failure.

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Unknown

AT-001 for Diabetic Cardiomyopathy

Q: What is the mechanism of action of this treatment?

Common treatments for cardiomyopathy include beta-blockers, ACE inhibitors, aldosterone antagonists, and aldose reductase inhibitors like AT-001. Beta-blockers reduce heart rate and blood pressure, decreasing the heart's workload. ACE inhibitors and aldosterone antagonists help relax blood vessels and reduce fluid buildup, improving heart function. Aldose reductase inhibitors, such as AT-001, target the enzyme aldose reductase, which is involved in glucose metabolism and can contribute to cardiac damage in diabetic cardiomyopathy. These treatments are crucial for managing symptoms, preventing disease progression, and improving the quality of life for cardiomyopathy patients.

Phase 3

Waitlist Available

Research Sponsored by Applied Therapeutics, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Type 2 Diabetes Mellitus

Peak VO2 < 75% of predicted normal value based on age and gender

Must not have

Severe or moderate cardiac valve disease requiring intervention

Clinically significant arrhythmia

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 15 months after randomization]

Awards & highlights

Pivotal Trial

Summary

This trial is testing a new drug called AT-001 to see if it can help adults with a heart condition related to diabetes. The goal is to improve their heart function or prevent it from getting worse, especially for those at high risk of severe heart failure.

Who is the study for?

This trial is for adults with Diabetic Cardiomyopathy who are at high risk of developing heart failure. Participants must have Type 2 Diabetes and reduced exercise capacity (Peak VO2 < 75% of normal). They can't join if they've had severe heart issues, uncontrolled blood pressure, or a history of significant cardiac events.

What is being tested?

The study tests the safety and effectiveness of AT-001 against a placebo in managing Diabetic Cardiomyopathy to prevent worsening into overt heart failure. It's conducted across multiple centers where participants are randomly assigned to either the drug or placebo group.

What are the potential side effects?

While specific side effects for AT-001 aren't listed here, common ones may include potential risks related to heart function, reactions at injection sites, gastrointestinal symptoms, and possible allergic reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have Type 2 Diabetes.

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My exercise capacity is less than 75% of what's expected for my age and gender.

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I have heart problems related to diabetes.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I need treatment for a serious heart valve problem.

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I have a serious irregular heartbeat.

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I have been diagnosed with a specific heart muscle condition before.

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I have had heart issues like a heart attack, bypass surgery, stent placement, or stroke.

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I have a severe condition that affects my ability to do a cardio-pulmonary exercise test.

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I have been diagnosed with or show signs of advanced heart failure.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 15 months after randomization]

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~15 months after randomization]

This trial's timeline: 3 weeks for screening, Varies for treatment, and 15 months after randomization] for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Peak VO2 during cardio-pulmonary exercise test (CPET);

Secondary study objectives

Changes in NT-proBNP

Changes in the modified Kansas City Cardiomyopathy Questionnaire (KCCQ) score

Progression to overt heart failure (Stage C Heart Failure)

Other study objectives

Changes in echocardiographic parameters

Worsening of diabetic cardiomyopathy

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

3Treatment groups

Experimental Treatment

Placebo Group

Group I: AT-001 Low DoseExperimental Treatment1 Intervention

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).

Group II: AT-001 High doseExperimental Treatment1 Intervention

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).

Group III: Placebo ComparatorPlacebo Group1 Intervention

Placebo capsules will be used as comparator

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

AT-001

2016

Completed Phase 2

~200

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for cardiomyopathy include beta-blockers, ACE inhibitors, aldosterone antagonists, and aldose reductase inhibitors like AT-001. Beta-blockers reduce heart rate and blood pressure, decreasing the heart's workload. ACE inhibitors and aldosterone antagonists help relax blood vessels and reduce fluid buildup, improving heart function. Aldose reductase inhibitors, such as AT-001, target the enzyme aldose reductase, which is involved in glucose metabolism and can contribute to cardiac damage in diabetic cardiomyopathy. These treatments are crucial for managing symptoms, preventing disease progression, and improving the quality of life for cardiomyopathy patients.