Sotagliflozin for Platelet Activation Control

Overseen By Amanda Prieur

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Michigan

Must not be taking: NSAIDs, Anticoagulants, SSRIs, SNRIs

Disqualifiers: Type I diabetes, Alcohol abuse, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 2 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how well sotagliflozin, a medication, controls platelet activation compared to other drugs that prevent blood cells from clumping together. The researchers seek to determine if sotagliflozin offers benefits in managing conditions linked to blood clots. Participants will receive either sotagliflozin or other common antiplatelet agents like aspirin, clopidogrel, or apixaban. Individuals who are generally healthy, not on certain medications like antidepressants or NSAIDs, and without a history of diabetes or certain infections, might be a good fit for this study.

As an Early Phase 1 trial, this research focuses on understanding how sotagliflozin works in people, offering participants the opportunity to contribute to groundbreaking medical knowledge.

Will I have to stop taking my current medications?

The trial requires that you stop taking NSAIDs (like Ibuprofen or Naproxen) at least 7 days before the study and anticoagulants 10 days before. You also cannot participate if you are currently taking SSRIs, SNRIs, lithium, or omeprazole/esomeprazole.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that sotagliflozin has promising safety results from past studies. In some studies, mice given sotagliflozin experienced less blood cell build-up and clotting, with no reported negative side effects, indicating good safety. Sotagliflozin also lowers the risk of stroke, providing an added benefit.

Other studies have used sotagliflozin with insulin, resulting in fewer heart problems, which suggests it works well with other treatments. Although this trial remains in the early stages, with limited safety data, these findings suggest sotagliflozin might be well-tolerated. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Sotagliflozin is unique because, unlike standard antiplatelet treatments like aspirin, clopidogrel, or apixaban, which primarily prevent blood clots, sotagliflozin targets platelet activation through a different mechanism. Researchers are excited about this treatment because it works by modulating glucose transport, offering a potentially novel way to control platelet function. This could lead to more tailored and effective strategies for managing platelet-related conditions, potentially with fewer side effects than current options.

What evidence suggests that sotagliflozin might be an effective treatment for platelet activation?

Research has shown that sotagliflozin, a type of medication, may help control platelet activation. Studies have found that it can reduce more than 50% of certain platelet activities, such as aggregation and chemical release, which are crucial in blood clot formation. As sotagliflozin dosage increases, platelet clumping noticeably decreases, potentially preventing unwanted blood clots. This suggests sotagliflozin might benefit individuals at risk for clot-related health issues. Additionally, evidence indicates heart and blood vessel benefits for those with type 2 diabetes and kidney disease, enhancing its potential usefulness.

In this trial, participants will receive sotagliflozin or antiplatelet agents such as aspirin, clopidogrel, or apixaban in a randomized order to assess platelet responsiveness. ^{1 5 6 7 8}

Who Is on the Research Team?

Michael Holinstat, PhD

Principal Investigator

University of Michigan

Are You a Good Fit for This Trial?

This trial is for individuals who can undergo platelet function tests to study the effects of different antiplatelet drugs. Specific inclusion and exclusion criteria details are not provided, so participants should consult with the trial organizers for eligibility.

Exclusion Criteria

Subjects with a history of alcohol abuse, pancreatitis or pancreatic surgery, or subjects taking a ketogenic diet

Subjects with a creatinine greater than or equal to 1.5 mg/dl will be excluded

Students under the direct supervision of Dr. Michael Holinstat

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single administration of sotagliflozin, aspirin, clopidogrel, or apixaban in randomized order

2 weeks

1 visit (in-person) every 14 days

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 is testing the antiplatelet effects of Sotagliflozin (SOTA) compared to three FDA-approved drugs: Aspirin, Clopidogrel, and Eliquis. Each drug will be followed by three others in a random order to assess their impact on platelet activation.

How Is the Trial Designed?

Group I: Platelet function in healthy subjects administered sotagliflozin vs. antiplatelet agents Experimental Treatment 4 Interventions

Platelet responsiveness will be assessed in the blood from subjects administered sotagliflozin, aspirin, clopidogrel, or apixaban in randomized order given as a single drug administration.

Who Is Running the Clinical Trial?

University of Michigan

Lead Sponsor

Trials

1,891

Recruited

6,458,000+

Lexicon Pharmaceuticals

Industry 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 significantly improves glycemic control in adults with type 1 diabetes, reducing HbA1c levels and insulin requirements while also enhancing time in the target glucose range, based on a meta-analysis of six trials involving 3,238 participants over 4 to 52 weeks.

While sotagliflozin reduces the incidence of hypoglycemia, it does increase the risk of diabetic ketoacidosis and other side effects, indicating that careful patient management and insulin dose adjustments are necessary to mitigate these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of dual SGLT 1/2 inhibitor sotagliflozin in type 1 diabetes: meta-analysis of randomised controlled trials. Musso, G., Gambino, R., Cassader, M., 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]

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 a 29-day study involving 33 patients with type 1 diabetes, sotagliflozin significantly reduced bolus insulin doses by 32.1% and improved glycemic control, as indicated by lower mean daily glucose levels and a decrease in HbA1c by 0.55%.

Sotagliflozin also increased the percentage of time patients spent in the target glucose range (70-180 mg/dL) to 68.2% and decreased time spent in the hyperglycemic range (>180 mg/dL) to 25%, all while promoting weight loss without increasing the risk of hypoglycemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotagliflozin, a Dual SGLT1 and SGLT2 Inhibitor, as Adjunct Therapy to Insulin in Type 1 Diabetes. Sands, AT., Zambrowicz, BP., Rosenstock, J., et al.[2022]

Sotagliflozin, a dual SGLT 1 and 2 inhibitor, has been shown to significantly reduce HbA1c levels in patients with type 1 diabetes when used alongside optimized insulin therapy, indicating its efficacy as a treatment option.

Despite its benefits, sotagliflozin is associated with a higher risk of diabetic ketoacidosis compared to placebo, which raised safety concerns during the FDA review process, leading to its approval only in the EU for specific patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotagliflozin: First Global Approval. Markham, A., Keam, SJ.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11950634/

Effects of sotagliflozin on kidney and cardiac outcome in a ... Sotagliflozin protects the kidney and heart in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD).

2. jacc.org jacc.org/doi/full/10.1016/S0735-1097(24)04222-0

SOTAGLIFLOZIN, A FIRST-IN-CLASS SGLT1/2 INHIBITOR, ... SOTA effectively inhibited more than 50% integrin activation and alpha granule secretion as assessed by expression of P-selectin.

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/3933/530190/Comparison-of-the-Anti-Platelet-and-Anti

Comparison of the Anti-Platelet and Anti-Thrombotic Effects of ... Increasing concentrations of SOTA result in a dose-dependent decrease in platelet aggregation, integrin αIIbβ3 activation and granule secretion ...

4. ahajournals.org ahajournals.org/doi/10.1161/circ.150.suppl_1.4134384

Abstract 4134384: Sotagliflozin, a Dual Inhibitor of Sodium- ... These results suggest a cardiovascular (CV) benefit of SOTA in patients with T2DM and CKD who are at increased risk of thromboembolic disease.

5. trial.medpath.com trial.medpath.com/clinical-trial/0e7914535d78db36/sotagliflozin-antiplatelet-effects-comparison

Comparison of Antiplatelet Effects of Sotagliflozin to FDA ... This study will identify the potential benefits of regulating platelet activation with sotagliflozin compared to other FDA-approved drugs known to limit ...

6. firstwordpharma.com firstwordpharma.com/story/5840212

Clinical Data on the Impact of Sotagliflozin on Stroke and ... Sotagliflozin reduced the risk of all-cause stroke by 34%, with 1.2 events per 100 patient-years in the sotagliflozin group and 1.8 events per ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12170572/

Safety and efficacy of adjuvant Sotagliflozin therapy in ... Sotagliflozin, when used in combination with insulin therapy, resulted in significant reductions in cardiovascular disease (CVD) risk (−6.38%; ...

8. uspharmacist.com uspharmacist.com/article/poster-reveals-how-sotagliflozin-generates-cardioprotective-effects

Poster Reveals How Sotagliflozin Generates ... In vivo studies showed that mice dosed with SOTA exhibited reduced platelet accumulation and fibrin formation, with no observed impact on ...