Sotagliflozin for Hypertrophic Cardiomyopathy

(SOTA-CROSS HCM Trial)

Overseen By Sharlene Day, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Pennsylvania

Must not be taking: SGLT2 inhibitors

Disqualifiers: Type 1 diabetes, Uncontrolled Afib, Severe lung disease, others

Compensation: Varies

Number of Visits: 8

26 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether sotagliflozin, a medication affecting sugar absorption, can treat symptoms of nonobstructive hypertrophic cardiomyopathy (noHCM), a condition where the heart muscle thickens abnormally. Researchers aim to determine if it improves exercise capacity and heart function compared to a placebo. Participants will take either the drug or a placebo daily for a period, then switch. This trial suits individuals with diagnosed noHCM who experience symptoms like reduced exercise capacity. As an Early Phase 1 trial, this research focuses on understanding how sotagliflozin works in people, offering participants a chance to be among the first to receive this treatment.

Will I have to stop taking my current medications?

The trial requires that participants have stable medical therapy for at least 1 month before joining, but it does not specify if you need to stop any current medications. It's best to discuss your specific medications with the trial team.

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

Research has shown that sotagliflozin has been studied in people with heart failure and diabetes. In those studies, most participants tolerated the drug well, experiencing few serious side effects. It also improved symptoms and quality of life for patients with heart issues. Although this trial targets a different condition, these past results suggest it might be safe.

Sotagliflozin has also been used safely for other conditions. The FDA has approved it for treating diabetes, indicating it has passed many safety tests. While this differs from the current study, it suggests the drug might be safe for people with hypertrophic cardiomyopathy as well.

This trial is in an early phase, focusing mainly on safety. While previous research is encouraging, this trial will provide more specific information about how people with this condition handle the drug. ^{1 2 3 4 5}

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

Sotagliflozin is unique because it targets sodium-glucose co-transporter (SGLT) pathways, which are not typically addressed by current treatments for hypertrophic cardiomyopathy. Most standard treatments for this condition focus on managing symptoms with beta-blockers, calcium channel blockers, or surgical interventions. Sotagliflozin, originally used for diabetes, offers a fresh approach by potentially improving heart function through its impact on glucose and sodium levels. Researchers are excited about its ability to address the underlying metabolic processes of the heart, which could lead to improved outcomes and quality of life for patients with hypertrophic cardiomyopathy.

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

Research has shown that sotagliflozin, a medication targeting specific proteins in the body, may help treat heart conditions. Studies have found that it can improve heart health by reducing major heart-related events. For patients with heart failure and weakened heart pumping ability, sotagliflozin treatment led to noticeable health improvements. It has also effectively reduced deaths from heart issues in people with diabetes. In this trial, participants will receive sotagliflozin in one phase and a placebo in another. These findings suggest that sotagliflozin could improve exercise ability and heart function in people with a condition where the heart muscle becomes too thick. ^{1 2 3 4 5}

Who Is on the Research Team?

Sharlene Day, MD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

Adults with nonobstructive hypertrophic cardiomyopathy (HCM) who can take oral medication, agree to use effective contraception if applicable, and have a stable medical therapy. They must have good heart function as shown by tests and be experiencing certain symptoms or reduced exercise capacity.

Inclusion Criteria

I have signed and dated the consent form.

I can take pills and will follow the study's treatment plan.

I have been using effective birth control for at least a month and agree to continue during and 2 weeks after the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase 1

Participants receive either sotagliflozin or placebo daily for 12 weeks

12 weeks

Visits every 4-12 weeks for checkups, surveys, and tests

Treatment Phase 2

Participants cross-over to receive the alternate treatment (sotagliflozin or placebo) for an additional 12 weeks

12 weeks

Visits every 4-12 weeks for checkups, surveys, and tests

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 trial is testing sotagliflozin against a placebo in patients with HCM. Participants will take the drug or placebo for 12 weeks, then switch to the other for another 12 weeks. The study checks if sotagliflozin improves tolerance, exercise ability, heart function, and cardiac markers.

How Is the Trial Designed?

Group I: Sotagliflozin first phase, Placebo second phase Active Control 1 Intervention

Sotagliflozin 400 mg once daily will be administered in the first phase, matching placebo once daily will be administered in the second phase

Group II: Placebo first phase, Sotagliflozin second phase Placebo Group 1 Intervention

Matching placebo once daily will be administered in the first phase, Sotagliflozin 400 mg once daily will be administered in the second phase

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

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]

Sotagliflozin significantly increases the risk of genital mycotic infections in both type 1 and type 2 diabetes patients, with a relative risk of 3.49 for type 1 and 2.83 for type 2, indicating a notable safety concern associated with its use.

The drug also raises the risk of acidosis-related events in type 1 diabetes patients, with a relative risk of 7.49 for diabetic ketoacidosis, while showing no increased risk for these events in type 2 diabetes patients, suggesting different safety profiles based on diabetes type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of sotagliflozin in the therapy of diabetes mellitus type 1 and type 2: A meta-analysis of randomized trials. Zhou, F., Du, N., Zhou, L., et al.[2022]

Sotagliflozin, a new medication for diabetes, was found to be safe for renal function, showing no significant adverse effects on kidney health in a review of 14 studies involving 17,574 participants, including those with existing renal impairment.

The drug did not significantly change urinary albumin excretion or the risk of composite renal events, indicating that while it is safe, more research is needed to fully understand its effectiveness in preventing diabetic kidney disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of the dual sodium-glucose co-transporter-1 and -2 inhibitor sotagliflozin on renal outcomes in type 1 diabetes and type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials. Bantounou, MA., Sardellis, P., Thuemmler, R., et al.[2023]

In a small study of 36 patients with type 2 diabetes and heart failure, canagliflozin showed improvements in lean peak oxygen consumption and ventilatory anaerobic threshold compared to sitagliptin, indicating potential benefits for cardiorespiratory fitness.

Although canagliflozin did not significantly improve the primary endpoints of peak oxygen consumption or VE/VCO2 slope, it did lead to a notable reduction in heart failure-related quality of life, suggesting it may still offer important benefits for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of canagliflozin compared to sitagliptin on cardiorespiratory fitness in type 2 diabetes mellitus and heart failure with reduced ejection fraction: The CANA-HF study. Carbone, S., Billingsley, HE., Canada, JM., et al.[2021]

Sodium-glucose co-transporter-2 inhibitors (SGLT2is) like dapagliflozin, empagliflozin, and sotagliflozin may help reduce hospitalizations and cardiovascular mortality in patients with heart failure with mildly reduced ejection fraction (HFmrEF), based on evidence from larger heart failure trials that included this subgroup.

Despite the promising potential of SGLT2is for HFmrEF, more dedicated trials are necessary to confirm their efficacy and understand the mechanisms behind their cardioprotective effects, as current evidence is limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Promise of sodium-glucose co-transporter-2 inhibitors in heart failure with mildly reduced ejection fraction. Shen, X., Shen, X.[2022]

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]

Sotagliflozin, a dual SGLT2 inhibitor, has been shown to significantly reduce the risk of cardiovascular death and hospitalizations for heart failure in patients with type 2 diabetes, as demonstrated in the SOLOIST-WHF trial.

In the SCORED trial, sotagliflozin not only lowered glycated hemoglobin levels in patients with severe renal impairment but also reduced the risk of stroke by 34%, highlighting its potential benefits across various stages of kidney disease and cardiovascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insights Into the Results of Sotagliflozin Cardiovascular Outcome Trials: Is Dual Inhibition the Cherry on the Cake of Cardiorenal Protection? Koufakis, T., Mustafa, OG., Tsimihodimos, V., et al.[2022]

Sotagliflozin demonstrated significant cardiovascular benefits in type 2 diabetes patients with heart failure, showing a reduction in heart failure events and major adverse cardiovascular events compared to other treatments like dapagliflozin and empagliflozin, based on a meta-analysis of 11 studies involving 30,952 patients.

The safety profile of sotagliflozin was acceptable, with no increased risk of diabetic ketoacidosis or urinary tract infections, although it did present a mild risk of diarrhea compared to placebo, making it a viable option for managing T2DM in patients with heart failure or cardiovascular risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular benefits and safety of sotagliflozin in type 2 diabetes mellitus patients with heart failure or cardiovascular risk factors: a bayesian network meta-analysis. Li, J., Zhu, C., Liang, J., 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]

Dapagliflozin, an SGLT2 inhibitor, has been shown to significantly reduce the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure with reduced ejection fraction (HFrEF), regardless of whether they have type 2 diabetes.

In the DAPA-HF trial, dapagliflozin was well tolerated and demonstrated a lower risk of worsening heart failure or cardiovascular death compared to placebo, making it a valuable treatment option for adults with symptomatic HFrEF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin: A Review in Symptomatic Heart Failure with Reduced Ejection Fraction. Blair, HA.[2022]

Citations

1. 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 ...

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. investors.lexpharma.com investors.lexpharma.com/news-releases/news-release-details/sotagliflozin-provides-consistent-relative-risk-reduction-heart

Release Details - Investor Relations | Lexicon Pharmaceuticals Sotagliflozin similarly reduced total MACE compared with placebo (5.7 vs 7.1 events/100 p-y; HR: 0.80), with consistent findings among adults < ...

4. jacc.org jacc.org/doi/10.1016/j.jacc.2024.06.036

Effects of Sotagliflozin on Health Status in Patients With ... Treatment with sotagliflozin vs placebo showed a 3.5-point (95% CI: 0.3–6.8 points) improvement in KCCQ-12 score in those with LVEF <50% and a ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2030183

Sotagliflozin in Patients with Diabetes and Recent ... Sotagliflozin therapy, initiated before or shortly after discharge, resulted in a significantly lower total number of deaths from cardiovascular causes and ...