Sodium Glucose Co-transporter (SGLT) Inhibitors in Nonobstructive Hypertrophic Cardiomyopathy

NCT06433050 | Recruiting Early Phase 1 DMC

• 2 other identifiers: 855065R61HL164376
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if sotagliflozin, a dual SGLT1 and SGLT2 inhibitor, works to treat symptomatic, nonobstructive hypertrophic cardiomyopathy (noHCM) in adult patients. It will also learn about the safety of sotagliflozin in this patient population. The main questions it aims to answer are:

1. 1.Will sotagliflozin be well tolerated in patients with nonobstructive HCM?
2. 2.Will sotaglifozin improve exercise capacity, diastolic dysfunction and/or physical functioning in patients with nonobstructive HCM?
3. 3.Will sotagliflozin improve circulating markers of cardiac metabolism in patients with nonobstructive HCM?

Conditions

Hypertrophic Cardiomyopathy Without Obstruction

Outcome Measures

Primary Outcomes (5)

• Number of participants with treatment-related adverse events

  Adverse event reporting

  Through study completion, 28 weeks

• Intracavitary obstruction

  Intracavitary left ventricular pressure gradient in mmHg

  Through study completion, 28 weeks

• Cardiac rhythm

  New occurrence of cardiac arrhythmia measured by ambulatory monitoring

  Through study completion, 28 weeks

• Maximal exercise capacity

  Peak oxygen consumption in mL/min

  Through study completion, 28 weeks

• Submaximal exercise capacity

  Stroke volume augmentation at exercise steady state in mL/min

  Through study completion, 28 weeks

Secondary Outcomes (9)

• Systolic function

  Through study completion, 28 weeks

• Contractility

  Through study completion, 28 weeks

• Diastolic function

  Through study completion, 28 weeks

• Left ventricular hypertrophy

  Through study completion, 28 weeks

• Symptom scores

  Through study completion, 28 weeks

Study Arms (2)

Placebo first phase, Sotagliflozin second phase

PLACEBO COMPARATOR

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

Drug: Sotagliflozin

Sotagliflozin first phase, Placebo second phase

ACTIVE COMPARATOR

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

Drug: Sotagliflozin

Interventions

Sotagliflozin DRUG

Sotagliflozin or placebo will be administered to each participant in a cross over study design. Each participant will receive active drug and placebo with randomization of the order in which they receive them.

Also known as: Inpefa

Placebo first phase, Sotagliflozin second phase; Sotagliflozin first phase, Placebo second phase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age at least 18 years, both sexes
• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Ability to take oral medication and be willing to adhere to the study intervention.
• For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 2 weeks after the end of administration of study drug.
• Diagnosis of HCM with NYHA Class II-III functional class or New York Heart Association (NYHA) Class I with peak VO2 \< 90% on cardiopulmonary exercise stress testing performed at Visit 1.
• Left ventricular outflow tract gradient \< 50 mmHg at rest, with valsalva, and with exercise.
• \. Left ventricular ejection fraction \> 50% by echocardiogram or cardiac MRI based on the most recent assessment in the past year prior to screening and confirmed during Visit 1 echocardiogram.
• \. Stable medical therapy for at least 1 month prior to study enrollment.

You may not qualify if:

• Receiving therapy with an SGLT2 inhibitor within 8 weeks prior to enrollment or previous intolerance of an SGLT2 inhibitor
• Type 1 diabetes mellitus
• Age \<18 years old
• Pregnant or lactating women: Women of childbearing potential will undergo a urine pregnancy test during the screening visit.
• Uncontrolled atrial fibrillation, as defined by a resting heart rate \> 100 beats per minute at the time of the baseline assessment
• Paroxysmal atrial fibrillation (Afib) or flutter with plans to attempt to restore sinus rhythm (with drug therapy, ablation, or DC cardioversion) during the study period.
• Unable to attain a respiratory exchange ratio of at least 1.05 on cardiopulmonary exercise test (CPET) on the day of screening.
• Septal reduction therapy within the previous 3 months.
• Implantable cardio-defibrillator (ICD) implantation planned during the study period.
• Implantation of a cardiac resynchronization therapy (CRT) device within 12 weeks prior to enrollment or intent to implant a CRT device during the study period
• Hemoglobin \< 10 g/dL
• Estimated glomerular filtration rate (eGFR) \< 25 mL/min/1.73m\^2, or unstable or rapidly progressing renal disease at the time of randomization
• Subject inability/unwillingness to exercise
• Greater than moderate left sided valvular disease (mitral regurgitation, aortic stenosis, aortic regurgitation), moderate or greater mitral stenosis, or severe right-sided valvular disease based on baseline echo at the time of enrollment
• Current angina due to clinically significant epicardial coronary disease, as per investigator judgment

Sponsors & Collaborators

• University of Pennsylvania: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

MeSH Terms

Interventions

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol

Study Officials

• Sharlene Day, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sharlene Day, MD

CONTACT

734-548-0394; sharlene.day@pennmedicine.upenn.edu

Kim Clinton

CONTACT

215-431-4545; kimberly.clinton@pennmedicine.upenn.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blinded
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Cardiovascular Medicine

Study Record Dates

• First Submitted: May 13, 2024
• First Posted: May 29, 2024
• Study Start: December 17, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: February 11, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)