Sotagliflozin: Sotagliflozin will be administered as a tablet(s), orally once daily.
Placebo: Placebo will be administered as a tablet(s) (identical to the sotagliflozin tablet in appearance), orally once daily.
Study summary
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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* KCCQ CSS \< 85.
* NYHA functional class II or III
* A diagnosis of HCM consistent with the current American College of Cardiology Foundation/American Heart Association and European Society of Cardiology guideline definition: unexplained left ventricular (LV) hypertrophy with nondilated ventricular chambers in the absence of other cardiac (eg, hypertension, aortic stenosis) or systemic disease with maximal LV wall thickness ≥ 15 millimeters (mm), or ≥ 13 mm with positive family history of HCM.
* For obstructive hypertrophic cardiomyopathy (oHCM), left ventricular outflow tract (LVOT) peak gradient ≥ 30 millimetre of mercury (mm Hg) during screening as assessed by echocardiography at rest or during a valsalva maneuver.
* For nonobstructive hypertrophic cardiomyopathy (nHCM), LVOT peak gradient \< 30 mm Hg during screening as assessed by echocardiography at rest and \< 30 mm Hg during a valsalva maneuver.
* Screening left ventricular ejection fraction (LVEF) ≥ 50%, except for those on a cardiac myosin inhibitor (screening LVEF ≥ 55%).
* For participants on a cardiac myosin inhibitor, the dose must be stable at least 3 months prior to screening. Participants on cardiac myosin inhibitor should not be scheduled for up-titration during the trial.
* Stable doses of background therapy (ie, β-blockers, calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, diuretics) for at least 1 month prior to screening.
Exclusion Criteria:
* Received therapy with a sodium glucose co-transporter 2 (SGLT2) inhibitor within the past 8 weeks prior to screening.
* Previous intolerance to an SGLT2 inhibitor.
* Any previous treatment with sotagliflozin.
* Current use of thiazolidinediones or digoxin.
* Current/planned participation in another interventional clinical trial or prior participation in any interventional trial with an investigational agent within 45 days of screening.
* Known infiltrative or storage disorder causing cardiac hypertrophy that mimics HCM such as Fabry disease, amyloidosis, or Noonan syndrome with LV hypertrophy.
* History of unexplained syncope within 6 months prior to screening.
* History of sustained ventricular tachyarrhythmia (\> 30 seconds) or appropriate implantable cardioverter defibrillator (ICD) discharge within 6 months prior to screening.
* Has paroxysmal, persistent, or permanent atrial fibrillation not on anticoagulation for at least 4 weeks prior to screening and/or not adequately rate controlled within 3 months of screening.
* Septal reduction therapy planned during the study period. For participants who had septal reduction therapy, the procedure should have been completed more than 3 months prior to screening.
* Cardiac surgery (eg, coronary artery bypass graft, valvular repair/replacement), percutaneous coronary intervention, or implantation of cardiac device (pacemaker or implantable cardioverter defibrillator) within 3 months prior to screening or planned during the study period.
* Presence of a cardiac resynchronization therapy device.
* Acute coronary syndrome within 2 months prior to screening.
* History of stroke or myocardial infarction within 6 months prior to screening.
* Hospitalization for heart failure or arrhythmia within 4 weeks prior to screening.
* Has known moderate or severe (as per investigator's judgment) aortic valve stenosis at screening.
* Current angina or clinically significant ischemia due to unstable epicardial coronary disease, as per investigator judgment.
Primary outcome measure(s)
Change from Baseline to Week 26 in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ CSS) — Baseline to Week 26 KCCQ is a 23-item, self-administered questionnaire that measure the participant's perception of their health status, including their heart failure (HF) symptoms, impact on physical and social function and how their HF impacts the quality of life. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores are generated for each domain and scaled from 0 to 100, with 0 denoting the worst and 100 the best possible status. Higher scores reflect better health status.
Trial sites (108)
Facility
City
Region
Status
Lexicon Investigational Site (4041)
Phoenix
Arizona
Lexicon Investigational Site (4037)
Scottsdale
Arizona
Lexicon Investigational Site (4012)
Los Angeles
California
Lexicon Investigational Site (4035)
Pomona
California
Lexicon Investigational Site (4044)
San Francisco
California
Lexicon Investigational Site (4046)
Jacksonville
Florida
Lexicon Investigational Site (4034)
Orlando
Florida
Lexicon Investigational Site (4018)
Atlanta
Georgia
Lexicon Investigational Site (4033)
Evanston
Illinois
Lexicon Investigational Site (4036)
Merrillville
Indiana
Lexicon Investigational Site (4021)
Baltimore
Maryland
Lexicon Investigational Site (4016)
Boston
Massachusetts
Lexicon Investigational Site (4042)
Boston
Massachusetts
Lexicon Investigational Site (4028)
Ann Arbor
Michigan
Lexicon Investigational Site (4038)
Grand Rapids
Michigan
Lexicon Investigational Site (4027)
Rochester
Minnesota
Lexicon Investigational Site (4013)
St Louis
Missouri
Lexicon Investigational Site (4029)
Morristown
New Jersey
Lexicon Investigational Site (4039)
Manhasset
New York
Lexicon Investigational Site (4043)
New York
New York
Lexicon Investigational Site (4026)
Morrisville
North Carolina
Lexicon Investigational Site (4031)
Cincinnati
Ohio
Lexicon Investigational Site (4017)
Cleveland
Ohio
Lexicon Investigational Site (4024)
Tulsa
Oklahoma
Lexicon Investigational Site (4015)
Portland
Oregon
Lexicon Investigational Site (4011)
Philadelphia
Pennsylvania
Lexicon Investigational Site (4019)
Germantown
Tennessee
Lexicon Investigational Stie (4014)
Houston
Texas
Lexicon Investigational Site (4032)
Charlottesville
Virginia
Lexicon Investigational Site (4045)
Seattle
Washington
Lexicon Investigational Site (4010)
Seattle
Washington
Lexicon Investigational Site (4022)
Marshfield
Wisconsin
Lexicon Investigational Site (4040)
Milwaukee
Wisconsin
Lexicon Investigational Site (5016)
Santa Rosa
La Pampa Province
Lexicon Investigational Site (5012)
Rosario
Santa Fe Province
Lexicon Investigational Site (5014)
Santa Fe
Santa Fe Province
Lexicon Investigational Site (5015)
Corrientes
Argentina
Lexicon Investigational Site (5010)
Córdoba
Argentina
Lexicon Investigational Site (5013)
Córdoba
Argentina
Lexicon Investigational Site (5011)
Salta
Argentina
+ 68 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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