Sotagliflozin for Hypertrophic Cardiomyopathy

(SONATA-HCM Trial)

Recruiting at 108 trial locations

Overseen By Tracy Newbold

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Lexicon Pharmaceuticals

Must be taking: Cardiac myosin inhibitors

Must not be taking: SGLT2 inhibitors, Thiazolidinediones, Digoxin

Disqualifiers: Atrial fibrillation, Stroke, Myocardial infarction, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 26 weeks

500 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the medication sotagliflozin can reduce symptoms and improve daily living for people with symptomatic hypertrophic cardiomyopathy (HCM), a condition where the heart muscle thickens abnormally. Participants will receive either sotagliflozin or a placebo (a pill with no active drug) to compare effects. Suitable candidates have been diagnosed with HCM and experience noticeable symptoms affecting daily activities. As a Phase 3 trial, this study is the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications. However, you must have stable doses of certain medications like β-blockers, calcium channel blockers, ACE inhibitors, angiotensin receptor blockers, and diuretics for at least 1 month before screening. You cannot use thiazolidinediones or digoxin, and you must not have used an SGLT2 inhibitor in the past 8 weeks.

Is there any evidence suggesting that sotagliflozin is likely to be safe for humans?

Research has shown that sotagliflozin has been studied for its effects on heart conditions. Patients have generally tolerated the treatment well. Other studies have tested sotagliflozin for heart issues and diabetes, indicating it is usually safe.

Reported side effects are usually mild and can include digestive problems like diarrhea and some changes in kidney function. Serious side effects are rare. This treatment works by affecting certain proteins that help control blood sugar and may also benefit the heart.

Since sotagliflozin has reached this stage of testing, earlier studies provide confidence in its safety. However, like any treatment, it's important to consider both the benefits and risks. Always discuss any concerns with a doctor before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for hypertrophic cardiomyopathy?

Researchers are excited about sotagliflozin for hypertrophic cardiomyopathy because it represents a novel approach compared to existing treatments like beta-blockers and calcium channel blockers. Unlike these traditional therapies, which mainly focus on symptom management, sotagliflozin is a dual SGLT1 and SGLT2 inhibitor. This unique mechanism targets glucose and sodium reabsorption in the kidneys, potentially offering benefits beyond heart function improvement, such as better metabolic control. This could mean a more comprehensive treatment option for patients with hypertrophic cardiomyopathy.

What evidence suggests that sotagliflozin might be an effective treatment for hypertrophic cardiomyopathy?

Research shows that sotagliflozin might help people with hypertrophic cardiomyopathy (HCM). In this trial, participants will receive either sotagliflozin or a placebo. Studies suggest sotagliflozin can improve heart function by addressing changes in heart structure and problems with heart relaxation. Sotagliflozin blocks two proteins, SGLT1 and SGLT2, which are important for heart and kidney health. Early findings indicate that this dual action could benefit heart conditions like HCM. Additionally, other heart-related studies have shown that sotagliflozin can lower the risk of heart failure and major heart problems. These promising results suggest that sotagliflozin could help manage symptoms and improve the quality of life for those with HCM. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with symptomatic hypertrophic cardiomyopathy (HCM), which is a condition where the heart muscle becomes abnormally thick. Participants should have symptoms and limitations due to HCM but specific inclusion and exclusion criteria details are not provided.

Inclusion Criteria

My heart condition causes a significant blockage in blood flow.

I have been diagnosed with HCM without any other heart or systemic disease.

KCCQ CSS < 85

Exclusion Criteria

I have had fainting spells in the last 6 months without a known reason.

I have a type of irregular heartbeat not treated with blood thinners for the last 4 weeks.

I am currently taking thiazolidinediones or digoxin.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Up to 3 weeks

Treatment

Participants receive either sotagliflozin or placebo for up to 26 weeks

26 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Sotagliflozin

Trial Overview The study aims to see if sotagliflozin, a medication, can improve symptoms and physical limitations in people with HCM compared to a placebo (a substance with no active drug).

How Is the Trial Designed?

Group I: Sotagliflozin Experimental Treatment 1 Intervention

Following an up to 3-week screening period, sotagliflozin 400 milligrams (mg) tablets will be administered as two 200 mg tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 26 weeks.

Group II: Placebo Placebo Group 1 Intervention

Following an up to 3-week screening period, sotagliflozin-matching placebo 400 mg tablets will be administered as two 200 mg tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 26 weeks.

Sotagliflozin is already approved in European Union, United States for the following indications:

Approved in European Union as Zynquista for:

• Type 1 diabetes mellitus

Approved in United States as Inpefa for:

• Heart failure
• Type 2 diabetes mellitus
• Chronic kidney disease

Who Is Running the Clinical Trial?

Lexicon Pharmaceuticals

Lead Sponsor

Trials

67

Recruited

24,400+

Dr. Mike Exton

Lexicon Pharmaceuticals

Chief Executive Officer

PhD in Neuroscience from the University of Newcastle and PhD in Immunology from the University of Essen, Germany

Dr. Craig Granowitz

Lexicon Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

Sotagliflozin, a dual SGLT1 and SGLT2 inhibitor, significantly improved glycemic control, reduced body weight, and lowered insulin requirements in adults with type 1 diabetes over 24 weeks, with benefits maintained for up to 52 weeks.

The drug is generally well tolerated and does not increase the risk of hypoglycemia, although it does carry a risk of diabetic ketoacidosis, making it a valuable adjunct to insulin therapy for overweight or obese patients with type 1 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotagliflozin: A Review in Type 1 Diabetes. Deeks, ED.[2020]

In a study of 5453 patients with type 2 diabetes and recent heart failure, only about 27.2% met the strict eligibility criteria for sotagliflozin, while around 62.8% were eligible under more pragmatic criteria, indicating a significant gap in trial eligibility versus real-world applicability.

Eligible patients for sotagliflozin had more severe heart failure and higher rates of cardiovascular events, suggesting that while the drug may be effective, its benefits could be particularly important for those with more advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eligibility for sotagliflozin in a real-world heart failure population based on the SOLOIST-WHF trial enrolment criteria: data from the Swedish heart failure registry. Becher, PM., Savarese, G., Benson, L., et al.[2023]

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have been shown to significantly reduce hospitalization and cardiovascular mortality in patients with heart failure with preserved ejection fraction (HFpEF), highlighting their efficacy in this common and serious condition.

The ongoing SOTA-P-CARDIA trial aims to determine if the benefits of the dual SGLT1/2 inhibitor sotagliflozin, previously observed in diabetic heart failure patients, can also be extended to non-diabetic patients with HFpEF, with a focus on changes in left ventricular mass and other important health metrics over a 6-month period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and Design of the SOTA-P-CARDIA Trial (ATRU-V): Sotagliflozin in HFpEF Patients Without Diabetes. Pérez, MS., Rodríguez-Capitán, J., Requena-Ibáñez, JA., et al.[2023]

SGLT2 inhibitors (SGLT2i) showed a trend towards reducing the risk of cardiovascular death or heart failure hospitalization compared to sacubitril/valsartan and vericiguat, indicating their potential effectiveness in heart failure treatment.

SGLT2i demonstrated the greatest reduction in heart failure hospitalization rates compared to standard care and vericiguat, suggesting they may be the most effective therapy among the treatments analyzed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relative Efficacy of Sacubitril-Valsartan, Vericiguat, and SGLT2 Inhibitors in Heart Failure with Reduced Ejection Fraction: a Systematic Review and Network Meta-Analysis. Aimo, A., Pateras, K., Stamatelopoulos, K., et al.[2022]

In the SOLOIST-WHF trial involving 1222 patients with type 2 diabetes and recent heart failure hospitalization, sotagliflozin significantly increased the days alive and out of the hospital (DAOH) by 3% compared to placebo, indicating its potential to improve patient outcomes.

Sotagliflozin reduced the rate of days dead by 29% (RR 0.71) rather than significantly decreasing hospitalizations, suggesting that its primary benefit lies in enhancing survival rather than just reducing hospital visits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Sotagliflozin on Total Hospitalizations in Patients With Type 2 Diabetes and Worsening Heart Failure : A Randomized Trial. Szarek, M., Bhatt, DL., Steg, PG., et al.[2021]

Sotagliflozin, the first dual inhibitor of SGLT1 and SGLT2, has shown significant efficacy in reducing cardiovascular and heart failure events in patients with type 2 diabetes, as demonstrated in the SOLOIST-WHF trial with a hazard ratio of 0.67.

While sotagliflozin expands treatment options for heart failure, existing SGLT2 inhibitors like dapagliflozin and empagliflozin have more robust evidence supporting their use, particularly in heart failure and chronic kidney disease, indicating that further research is needed to clarify sotagliflozin's role in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotagliflozin: Efficacy, Safety, and Potential Therapeutic Applications in Heart Failure. Long, A., Salvo, M.[2023]

In the CREDENCE trial, canagliflozin significantly reduced the risk of hospitalization for heart failure or cardiovascular death by 31%, demonstrating its efficacy in patients with type 2 diabetes and chronic kidney disease.

The benefits of canagliflozin were more pronounced in high-risk groups, such as those with existing cardiovascular disease or advanced kidney disease, indicating that it is particularly effective for patients who are at greater risk of heart failure or cardiovascular events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of canagliflozin on heart failure and cardiovascular death by baseline participant characteristics: Analysis of the CREDENCE trial. Arnott, C., Li, JW., Cannon, CP., et al.[2021]

Citations

1. investors.lexpharma.com investors.lexpharma.com/news-releases/news-release-details/data-demonstrating-unique-benefits-sotagliflozin-diverse-patient

Release Details - Investor Relations | Lexicon Pharmaceuticals Data Demonstrating Unique Benefits of Sotagliflozin in Diverse Patient Populations will be Presented at the Hypertrophic Cardiomyopathy Society ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06481891

NCT06481891 | A Study to Evaluate the Efficacy and ... The main purpose of the study is to determine the changes in symptoms and functional limitations in participants with symptomatic hypertrophic ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1071916424003087

A Randomized, Double-Blind, Placebo-Controlled, Parallel ... The SONATA-HCM is a Phase 3, randomized, double-blind, placebo-controlled multicenter trial that will evaluate efficacy of sotagliflozin, a dual SGLT1 and SGLT2 ...

4. finance.yahoo.com finance.yahoo.com/news/data-demonstrating-unique-benefits-sotagliflozin-133000254.html

Data Demonstrating Unique Benefits of Sotagliflozin in ... Dual SGLT1 and 2 Inhibition with Sotagliflozin Ameliorates Adverse Cardiac Remodeling and Diastolic Dysfunction in Mice with HCM Due to ...

5. biospace.com biospace.com/press-releases/sotagliflozin-provides-consistent-relative-risk-reduction-in-heart-failure-and-major-cardiovascular-events-across-all-age-ranges-including-greater-than-75-in-data-presented-at-the-european-society-of-cardiology-esc-2025-congress

Sotagliflozin Provides Consistent Relative Risk Reduction ... Oral presentation highlighted improvements in heart failure endpoints and major adverse cardiovascular events (MACE) among older adults ...

6. adventhealth.com adventhealth.com/institute/adventhealth-research-institute/heart-lung-and-vascular-research/clinical-trials/4390-lx42111-314-hcm-a-randomized-double-blind-placebo-controlled-parallel-group-multicenter-study

LX4211.1-314-HCM - A Randomized, Double-blind, ... The purposes of this study are: to determine if the study drug is effective in treating symptoms related to HCM; to determine how well the study drug is ...

7. clinicaltrials.cedars-sinai.edu clinicaltrials.cedars-sinai.edu/view/LX4211-1-314-HCM

Sotagliflozin in Symptomatic Obstructive And Non-Obstructive ... The purpose of this study is to determine whether an experimental drug called sotagliflozin is effective in treating symptoms related to hypertrophic.