Sotagliflozin in Patients With Heart Failure Symptoms and Type 1 Diabetes

Prior treatment

• Use of sotagliflozin or any SGLT2 inhibitor within 1 month of screening or between screening and randomisation.
• Previous hypersensitivity/intolerance to SGLT2 inhibitors.
• Severe hypoglycaemia (hospitalisation for hypoglycaemia or episode requiring external assistance to treat) within 1 month prior to screening or between screening and randomisation.
• Use of any investigational drugs within five times of the elimination half-life after the last dose or within 30 days, whichever is longer. Current enrolment in non-interventional, observational studies will be allowed.

Other illness

• Cardiac surgery (coronary artery bypass graft or valve replacement), type 1 myocardial infarction, implantation of cardiac device (including biventricular pacemaker) or cardiac mechanical support implantation within 1 month of screening, or between screening and randomisation, or planned during the trial.
• End-stage heart failure requiring left ventricular assist devices, intra-aortic balloon pump, or any type of mechanical support at the time of randomisation.
• Documented primary severe valvular heart disease, amyloidosis or hypertrophic cardiomyopathy as principal cause of heart failure as judged by the local investigator.
• Respiratory disease thought to be the primary cause of dyspnoea as assessed by the local investigator.
• Chronic kidney disease with estimated glomerular filtration rate \<25ml/min/1.73m2 at screening.
• Moderate or severe hepatic impairment (e.g. Child-Pugh B and C) at screening as judged by the local investigator.
• Presence of malignancy with expected life expectancy \<1 year at screening.

Lab values

• Unwilling/unable to share glucose and ketone monitoring data.

Age

• Women of childbearing age or male partners of women of childbearing age and not practicing an acceptable method of birth control, see section 8.11

Other

• One episode of diabetic ketoacidosis or nonketotic hyperosmolar state within 1 month of screening or between screening and randomisation, or ≥2 diabetic ketoacidosis or nonketotic hyperosmolar state events within 6 months of screening.
• Pregnant or lactating women.
• On a ketogenic diet.

• Age 18 years to \<85 years.
• Type 1 diabetes.
• Insulin dose ≥0.5 units/kg body weight at screening or BMI ≥25kg/m2 at screening
• Using continuous glucose monitor at screening or willing to use one for the duration of the trial.
• Diagnosis of heart failure (HF) or high-risk for HF, defined as any of the following:
  • NT-proBNP ≥250ng/L for those in atrial fibrillation/flutter, ≥125 ng/L for those in all other rhythms or
  • Previous HF hospitalisation where HF was documented as the primary cause of hospitalisation and there was a requirement for loop diuretics or Impaired left ventricular (LV) function (i.e. LVEF \<50% by any imaging modality) at any time or Preserved LV systolic function (LVEF ≥50%) with left atrial enlargement (2-dimensional measurement of left atrial width ≥3.8cm or left atrial length ≥5.0 cm or left atrial area ≥20cm2 or left atrial volume index \>29 ml/m2) within the last 24 months.
  • or Preserved LV systolic function (LVEF ≥50%) with left ventricular hypertrophy (2-dimensional measurement of end-diastolic interventricular septal diameter ≥1.2cm or end-diastolic left ventricular posterior wall diameter ≥1.2cm) within the last 24 months.
  • or Preserved LV systolic function (LVEF ≥50%) with diastolic dysfunction (septal e' \<7cm/sec or lateral e' \<10cm/sec or average E/e' ≥15) within the last 24 months.
• New York Heart Association Class II-IV at screening.
• Kansas City Cardiomyopathy clinical summary score \<85 at screening.