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Active, not recruitingNCT06481891SONATA-HCMUpdated Aug 26, 2026

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

A Phase 3 interventional study of Sotagliflozin and Placebo in Obstructive Cardiomyopathy, Hypertrophic and Non-obstructive Hypertrophic Cardiomyopathy, sponsored by Lexicon Pharmaceuticals. Active, not recruiting at 108 sites in 19 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-26.

Sponsored by Lexicon Pharmaceuticals · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
500
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

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.

02

Conditions studied

  • Obstructive Cardiomyopathy, Hypertrophic
  • Non-obstructive Hypertrophic Cardiomyopathy
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts 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

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.
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
500 participants (estimated)

Study arms

  • Experimental
    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

  • Placebo comparator
    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

Interventions

  • DrugSotagliflozin

    Sotagliflozin will be administered as a tablet(s), orally once daily.

    Also known as: SAR439954/LX4211

  • DrugPlacebo

    Placebo will be administered as a tablet(s) (identical to the sotagliflozin tablet in appearance), orally once daily.

    Also known as: SAR439954/LX4211

05

What researchers measure

Primary outcomes

  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.

    Time frame: Baseline to Week 26

Secondary outcomes

  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.

    Time frame: Week 26

  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.

    Time frame: Baseline to Week 26

06

Study locations

108 sites
  • Lexicon Investigational Site (4041)
    Phoenix, Arizona 85054, United States
  • Lexicon Investigational Site (4037)
    Scottsdale, Arizona 85260, United States
  • Lexicon Investigational Site (4012)
    Los Angeles, California 90048, United States
  • Lexicon Investigational Site (4035)
    Pomona, California 91767, United States
  • Lexicon Investigational Site (4044)
    San Francisco, California 94143, United States
  • Lexicon Investigational Site (4046)
    Jacksonville, Florida 32224, United States
  • Lexicon Investigational Site (4034)
    Orlando, Florida 32804, United States
  • Lexicon Investigational Site (4018)
    Atlanta, Georgia 30322, United States
  • Lexicon Investigational Site (4033)
    Evanston, Illinois 60208, United States
  • Lexicon Investigational Site (4036)
    Merrillville, Indiana 46410, United States
  • Lexicon Investigational Site (4021)
    Baltimore, Maryland 21218, United States
  • Lexicon Investigational Site (4016)
    Boston, Massachusetts 02115, United States
  • Lexicon Investigational Site (4042)
    Boston, Massachusetts 02118, United States
  • Lexicon Investigational Site (4028)
    Ann Arbor, Michigan 48109, United States
  • Lexicon Investigational Site (4038)
    Grand Rapids, Michigan 49525, United States
  • Lexicon Investigational Site (4027)
    Rochester, Minnesota 55905, United States
  • Lexicon Investigational Site (4013)
    St Louis, Missouri 63110, United States
  • Lexicon Investigational Site (4029)
    Morristown, New Jersey 07960, United States
  • Lexicon Investigational Site (4039)
    Manhasset, New York 11030, United States
  • Lexicon Investigational Site (4043)
    New York, New York 10016, United States
  • Lexicon Investigational Site (4026)
    Morrisville, North Carolina 27560, United States
  • Lexicon Investigational Site (4031)
    Cincinnati, Ohio 45219, United States
  • Lexicon Investigational Site (4017)
    Cleveland, Ohio 44195, United States
  • Lexicon Investigational Site (4024)
    Tulsa, Oklahoma 74104, United States
  • Lexicon Investigational Site (4015)
    Portland, Oregon 97239, United States
  • Lexicon Investigational Site (4011)
    Philadelphia, Pennsylvania 19104, United States
  • Lexicon Investigational Site (4019)
    Germantown, Tennessee 38138, United States
  • Lexicon Investigational Stie (4014)
    Houston, Texas 77030, United States
  • Lexicon Investigational Site (4032)
    Charlottesville, Virginia 22908, United States
  • Lexicon Investigational Site (4045)
    Seattle, Washington 98101, United States
  • Lexicon Investigational Site (4010)
    Seattle, Washington 98195, United States
  • Lexicon Investigational Site (4022)
    Marshfield, Wisconsin 54449, United States
  • Lexicon Investigational Site (4040)
    Milwaukee, Wisconsin 53215, United States
  • Lexicon Investigational Site (5016)
    Santa Rosa, La Pampa Province L6304BWE, Argentina
  • Lexicon Investigational Site (5012)
    Rosario, Santa Fe Province 2000, Argentina
  • Lexicon Investigational Site (5014)
    Santa Fe, Santa Fe Province 3000, Argentina
  • Lexicon Investigational Site (5015)
    Corrientes, W3400CDS, Argentina
  • Lexicon Investigational Site (5010)
    Córdoba, 5002, Argentina
  • Lexicon Investigational Site (5013)
    Córdoba, X5000AAX, Argentina
  • Lexicon Investigational Site (5011)
    Salta, 4400, Argentina
  • Lexicon Investigational Site (1012)
    Genk, 3600, Belgium
  • Lexicon Investigational Site (5114)
    Salvador, Estado de Bahia 40170-130, Brazil
  • Lexicon Investigational Site (5110)
    Campinas, São Paulo 13060-080, Brazil
  • Lexicon Investigational Site (5112)
    Recife, 52051-380, Brazil
  • Lexicon Investigational Site (5115)
    São Paulo, 04039-000, Brazil
  • Lexicon Investigational Site (1112)
    Rousse, 7013, Bulgaria
  • Lexicon Investigational Site (1111)
    Sofia, 1407, Bulgaria
  • Lexicon Investigational Site (1215)
    Krapinske Toplice, 49217, Croatia
  • Lexicon Investigational Site (1212)
    Opatija, 51410, Croatia
  • Lexicon Investigational Site (1210)
    Rijeka, 51000, Croatia
  • Lexicon Investigational Site (1213)
    Zagreb, 10000, Croatia
  • Lexicon Investigational Site (1311)
    Brno, 602 00, Czechia
  • Lexicon Investigational Site (1310)
    Prague, 128 08, Czechia
  • Lexicon Investigational Site (1312)
    Ústí nad Labem, 400 11, Czechia
  • Lexicon Investigational Site (1514)
    Chambray-lès-Tours, 37170, France
  • Lexicon Investigational Site (1511)
    Marseille, 13005, France
  • Lexicon Investigational Site (1513)
    Paris, 75651, France
  • Lexicon Investigational Site (1510)
    Poitiers, 86021, France
  • Lexicon Investigational Site (1512)
    Rennes, 35033, France
  • Lexicon Investigational Site (1515)
    Toulouse, 31059, France
  • Lexicon Investigational Site (1611)
    Tbilisi, 0112, Georgia
  • Lexicon Investigational Site (1610)
    Tbilisi, 0131, Georgia
  • Lexicon Investigational Site (1612)
    Tbilisi, 0144, Georgia
  • Lexicon Investigational Site (1613)
    Tbilisi, 0186, Georgia
  • Lexicon Investigational Site (2813)
    Berlin, 13353, Germany
  • Lexicon Investigational Site (2812)
    Hamburg, 22041, Germany
  • Lexicon Investigational Site (2811)
    Leipzig, 04289, Germany
  • Lexicon Investigational Site (2810)
    München, 80336, Germany
  • Lexicon Investigational Site (1710)
    Budapest, 1122, Hungary
  • Lexicon Investigational Site (1711)
    Pécs, 7624, Hungary
  • Lexicon Investigational Site (1712)
    Szeged, 6725, Hungary
  • Lexicon Investigational Site (1713)
    Zalaegerszeg, 8900, Hungary
  • Lexicon Investigational Site (7017)
    Be’er Ya‘aqov, 7033001, Israel
  • Lexicon Investigational Site (7013)
    Haifa, 3109601, Israel
  • Lexicon Investigational Site (7014)
    Haifa, 3339419, Israel
  • Lexicon Investigational Site (7015)
    Holon, 5822012, Israel
  • Lexicon Investigational Site (7011)
    Jerusalem, 9112001, Israel
  • Lexicon Investigational Site (7016)
    Petah Tikva, 4941492, Israel
  • Lexicon Investigational Site (7012)
    Ramat Gan, 5265601, Israel
  • Lexicon Investigational Site (7019)
    Tel Aviv, 6423906, Israel
  • Lexicon Investigational Site (1814)
    Arezzo, 52100, Italy
  • Lexicon Investigational Site (1811)
    Brescia, 25123, Italy
  • Lexicon Investigational Site (1813)
    Naples, 80131, Italy
  • Lexicon Investigational Site (2114)
    Lodz, 91-347, Poland
  • Lexicon Investigational Site (2113)
    Lodz, 92-213, Poland
  • Lexicon Investigational Site (2115)
    Oświęcim, 32-600, Poland
  • Lexicon Investigational Site (2110)
    Wroclaw, 50-981, Poland
  • Lexicon Investigational Site (2210)
    Braga, 4710-243, Portugal
  • Lexicon Investigational Site (2213)
    Faro, 8000-386, Portugal
  • Lexicon Investigational Site (2211)
    Lisbon, 1350-352, Portugal
  • Lexicon Investigational Site (2215)
    Lisbon, 1500-650, Portugal
  • Lexicon Investigational Site (2218)
    Lisbon, 1649-035, Portugal
  • Lexicon Investigational Site (2216)
    Lisbon, 1998-018, Portugal
  • Lexicon Investigational Site (2217)
    Porto, 4200-319, Portugal
  • Lexicon Investigational Site (2910)
    Baloteşti, 077015, Romania
  • Lexicon Investigational Site (2913)
    Suceava, 720049, Romania
  • Lexicon Investigational Site (2911)
    Târgu Mureş, 540124, Romania
  • Lexicon Investigational Site (2912)
    Târgu Mureş, 540143, Romania
  • Lexicon Investigational Site (2312)
    Belgrade, 11000, Serbia
  • Lexicon Investigational Site (2314)
    Belgrade, 11000, Serbia

Showing the first 100 of 108 sites across 19 countries.

07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT06481891
Lead sponsor
Lexicon Pharmaceuticals
Responsible party
Sponsor
First posted
Jul 1, 2024
Start date
Sep 24, 2024
Primary completion
Jan 2027 (estimated)
Completion
Feb 2027 (estimated)
Last update
Aug 26, 2026

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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