Sotagliflozin for Hypertrophic Cardiomyopathy

(SONATA-HCM Trial)

Recruiting at 31 trial locations

Overseen By Tracy Newbold

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

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)

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

The main purpose of the study is to determine the changes in symptoms and functional limitations in participants with symptomatic hypertrophic cardiomyopathy (HCM) treated with sotagliflozin as compared to placebo.

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.

What data supports the idea that Sotagliflozin for Hypertrophic Cardiomyopathy is an effective drug?

The available research shows that Sotagliflozin has been effective in treating heart failure in patients with type 2 diabetes, as demonstrated in the SOLOIST-WHF trial. While the research does not specifically mention Hypertrophic Cardiomyopathy, the drug has shown benefits in heart failure management, which may suggest potential effectiveness for related heart conditions. However, there is no direct data provided on its use for Hypertrophic Cardiomyopathy specifically. ^{1 2 3 4 5}

What safety data exists for sotagliflozin?

Sotagliflozin has been evaluated for safety in various clinical trials. In the inTANDEM 1-3 trials for type 1 diabetes, it was generally well tolerated, though it carries a risk of diabetic ketoacidosis. In heart failure studies, such as the SOLOIST-WHF trial, it demonstrated efficacy and safety in patients with type 2 diabetes and heart failure. The SOTA-P-CARDIA trial is investigating its safety and efficacy in non-diabetic heart failure patients. Overall, sotagliflozin has shown a favorable safety profile in these contexts. ^{1 2 4 5 6}

Is the drug Sotagliflozin a promising treatment for Hypertrophic Cardiomyopathy?

Sotagliflozin shows promise as it has been effective in improving heart health in patients with heart failure and diabetes. It reduces hospital visits and heart-related deaths, which suggests it could be beneficial for heart conditions like Hypertrophic Cardiomyopathy. ^{1 4 5 6 7}

Eligibility Criteria

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.

KCCQ CSS < 85

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

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.

Trial Timeline

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

Treatment Details

Interventions

• Sotagliflozin (SGLT2 Inhibitor)

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).

Participant Groups

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.

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

Findings from Research

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]

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 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]

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]

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]

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]

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]

References

1. England 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. [2023]

2. United States 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. [2022]

3. England pubmed.ncbi.nlm.nih.gov

The effects of canagliflozin on heart failure and cardiovascular death by baseline participant characteristics: Analysis of the CREDENCE trial. [2021]

4. New Zealand pubmed.ncbi.nlm.nih.gov

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

5. United States pubmed.ncbi.nlm.nih.gov

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

6. United States pubmed.ncbi.nlm.nih.gov

Rationale and Design of the SOTA-P-CARDIA Trial (ATRU-V): Sotagliflozin in HFpEF Patients Without Diabetes. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Effect of Sotagliflozin on Total Hospitalizations in Patients With Type 2 Diabetes and Worsening Heart Failure : A Randomized Trial. [2021]