A Study to Evaluate the Efficacy and Safety of Sotagliflozin in Symptomatic Obstructive and Non-obstructive Hypertrophic Cardiomyopathy

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified January 2026 by Lexicon Pharmaceuticals
Sponsor
Lexicon Pharmaceuticals
Information Provided by (Responsible Party)
Lexicon Pharmaceuticals
Clinicaltrials.gov Identifier
NCT06481891
Other Study ID Numbers:
LX4211.1-314-HCM
First Submitted
June 24, 2024
First Posted
June 30, 2024
Last Update Posted
February 26, 2026
Last Verified
January 2026

ClinicalTrials.gov processed this data on February 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
Obstructive Cardiomyopathy, HypertrophicNon-obstructive Hypertrophic Cardiomyopathy
Drug: SotagliflozinDrug: Placebo

Study Design

Study TypeInterventional
Actual Enrollment500 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingQuadruple
Primary PurposeTreatment
Official TitleA Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy and Safety of SOtaglifloziN in symptomATic Obstructive And Non-obstructive Hypertrophic CardioMyopathy (SONATA-HCM)
Study Start DateSeptember 23, 2024
Actual Primary Completion Date1mo 1w from now
Actual Study Completion Date2mos 2w from now

Groups and Cohorts

Group/CohortIntervention/Treatment
Sotagliflozin
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.
Drug: Sotagliflozin
Sotagliflozin will be administered as a tablet(s), orally once daily.
Placebo
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.
Drug: Placebo
Placebo will be administered as a tablet(s) (identical to the sotagliflozin tablet in appearance), orally once daily.

Outcome Measures

Primary Outcome Measures
  1. Change from Baseline to Week 26 in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ CSS)
    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.
Secondary Outcome Measures
  1. Percentage of Participants at Week 26 with a New York Heart Association (NYHA) Functional Class Improvement ≥ 1 Category
    NYHA functional class is a clinician-reported assessment of participants' health status on a 4-point scale, where Class I represents no limitations in normal activity; Class II indicates slight limitation of physical activity; Class III indicates marked limitation in physical activity; and Class IV indicates that participants have symptoms with any physical activity or at rest. Percentage of participants with NYHA functional class improvement ≥1 will be reported.
  2. Change from Baseline to Week 26 in KCCQ Total Symptom Score (TSS).
    KCCQ is a 23-item, self-administered questionnaire that measure the participant's perception of their health status, including their 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.

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
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.

Contacts and Locations

Sponsors and CollaboratorsLexicon Pharmaceuticals
Locations
Lexicon Investigational Site (4041) | Phoenix Arizona, United States, 85054Lexicon Investigational Site (4037) | Scottsdale Arizona, United States, 85260Lexicon Investigational Site (4012) | Los Angeles California, United States, 90048Lexicon Investigational Site (4035) | Pomona California, United States, 91767Lexicon Investigational Site (4044) | San Francisco California, United States, 94143Lexicon Investigational Site (4046) | Jacksonville Florida, United States, 32224Lexicon Investigational Site (4034) | Orlando Florida, United States, 32804Lexicon Investigational Site (4018) | Atlanta Georgia, United States, 30322Lexicon Investigational Site (4033) | Evanston Illinois, United States, 60208Lexicon Investigational Site (4036) | Merrillville Indiana, United States, 46410Lexicon Investigational Site (4021) | Baltimore Maryland, United States, 21218Lexicon Investigational Site (4016) | Boston Massachusetts, United States, 02115Lexicon Investigational Site (4042) | Boston Massachusetts, United States, 02118Lexicon Investigational Site (4028) | Ann Arbor Michigan, United States, 48109Lexicon Investigational Site (4038) | Grand Rapids Michigan, United States, 49525Lexicon Investigational Site (4027) | Rochester Minnesota, United States, 55905Lexicon Investigational Site (4013) | St Louis Missouri, United States, 63110Lexicon Investigational Site (4029) | Morristown New Jersey, United States, 07960Lexicon Investigational Site (4039) | Manhasset New York, United States, 11030Lexicon Investigational Site (4043) | New York New York, United States, 10016Lexicon Investigational Site (4026) | Morrisville North Carolina, United States, 27560Lexicon Investigational Site (4031) | Cincinnati Ohio, United States, 45219Lexicon Investigational Site (4017) | Cleveland Ohio, United States, 44195Lexicon Investigational Site (4024) | Tulsa Oklahoma, United States, 74104Lexicon Investigational Site (4015) | Portland Oregon, United States, 97239Lexicon Investigational Site (4011) | 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