SOTAGLIFLOZIN for Post-bariatric hypoglycaemia

Inclusion criteria

• {"criterion_text":"- Age 18-74 years\n- RYGB-operation conducted >18 months ago\n- History of postprandial neuroglycopenia one–to–three hours after meal intake with subsequent relief after carbohydrate ingestion (per interview)\n- Documented postprandial episodes of level 2 hypoglycaemia (interstitial glucose concentration (IG) <3.0 mmol/l for ≥15 min, ≥2 times/week) assessed by 12-14 days of blinded CGM recording\n- Haemoglobin levels for women >7.3 mmol/l and for men > 8.3 mmol/l\n- Fasting plasma glucose concentration >3.5 mmol/l\n- Sinus rhythm at screening and no medical history of cardiac arrhythmias or cardiac ischaemia\n- Negative urine human chorionic gonadotropin (hCG) (for fertile women)"}

Exclusion criteria

• {"criterion_text":"- Treatment with medication(s) affecting insulin secretion, glucose metabolism, or any antidiabetic drugs\n- History of hypersensitivity or allergic reaction to sotagliflozin or any of the excipients\n- Known or suspected allergies to SGLT-2 inhibitors or related products\n- History of ketoacidosis\n- History of chronic kidney disease or an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2\n- Current participation in another clinical trial with administration of an investigational drug\n- Pregnancy or breastfeeding\n- Glycated haemoglobin (HbA1c) ≥48 mmol/mol\n- Major surgery within 30 days before screening\n- Alcohol abuse (per investigator assessment)\n- Any factors that, in the opinion of the site principal investigator or clinical protocol chair, would interfere with the safe completion of the study, including medical conditions that may require hospitalization during the trial"}

Primary endpoints

• {"endpoint_text":"- Time (% or minutes/per day) in level 2 hypoglycaemia (IG < 3.0 mmol/l) assessed by CGM during the out-patient part (Sotagliflozin 400 mg QD versus placebo)","definition_or_measurement_approach":"Assessed by continuous glucose monitoring (CGM) during the out-patient part; level 2 hypoglycaemia defined as interstitial glucose (IG) < 3.0 mmol/l; measured as time (percentage or minutes per day) spent in this range comparing sotagliflozin 400 mg QD versus placebo."}

Secondary endpoints

• {"endpoint_text":"- Time (% or minutes/per day) in level 1 hypoglycaemia (IG 3.0–3.9 mmol/l) (out-patient part)\n- Time (% or minutes/per day) below range (IG < 3.9 mmol/l, including readings <3.0 mmol/l) (out-patient part)\n- Time (% or minutes/per day) in range (IG 3.9–10.0 mmol/l) (out-patient part)\n- Time (% or minutes/per day) above tight range (>7.8 mmol/l) (out-patient part)\n- Time (% or minutes/per day) above range (>10.0 mmol/l) (out-patient part)\n- Time (% or minutes/per day) above range (>13.9 mmol/l) (out-patient part)\n- Frequency (no of events/day) of hypoglycaemic events (IG < 3.9 mmol/l, ≥15 min) (out-patient part)\n- Frequency (no of events/day) of level 1 hypoglycaemic events (IG 3.0–3.9 mmol/l, ≥15 min) (out-patient part)\n- Frequency (no of events/day) of level 2 hypoglycaemic events (IG <3.0 mmol/l, ≥15 min) (out-patient part)\n- Frequency (no of events/day) of hyperglycaemic events (>10.0 mmol/l, ≥15 min) (out-patient part)\n- Glycaemic variability assessed as coefficient of variation (CV) (out-patient part)\n- Glycaemic variability assessed as standard deviation (SD) (out-patient part)\n- Glycaemic variability assessed as low blood glucose index (LBGI) (out-patient part)\n- Change in full score of Edinburgh Hypoglycaemia Symptom scale during treatment (EHSS) (out-patient part)\n- Change in full score of fear of hypoglycaemia as assessed by Hypoglycaemia Fear Scale (HFS-II) (out-patient part)\n- Change in full score of quality of life as assessed by the 36-item Short Form health survey (SF-36) (out-patient part)\n- Nadir plasma glucose assessed as the absolute lowest value (in-patient part)\n- Time spent in hypoglycaemia (<3.9 mmol/l) (in-patient part)\n- Time spent in level 1 and level 2 hypoglycaemia (3.0–3.9 and < 3.0 mmol/l, respectively) (in-patient part)\n- Change in full score of Edinburgh Hypoglycemia Symptom scale (in-patient part)\n- Glycaemic rescue intervention due to critically low plasma glucose concentration (≤ 1.8 mmol/l) or onset of marked neuroglycopenic symptoms (in-patient part)\n- Time spent in hyperglycaemia (>7.8, >10.0 and 13.9 mmol/l, respectively) (in-patient part)\n- Peak plasma glucose concentration (in-patient part)\n- Changes in plasma / serum concentrations of insulin, C-peptide, glucagon, GLP-1, GIP, epinephrine, norepinephrine, somatotropin, pancreatic polypeptide, and cortisol measured as area under the curve (AUC) and/or incremental (iAUC) as appropriate, peak values and values at nadir plasma glucose concentration (in-patient part)\n- Rate of gastric emptying as assessed by acetaminophen concentration (paracetamol): Tmax and Cmax (in-patient part)","definition_or_measurement_approach":"Most secondary endpoints are assessed by CGM (time in ranges, frequency of events, variability metrics CV and SD, LBGI) during out-patient and in-patient parts. Patient-reported scales (EHSS, HFS-II, SF-36) use full score changes. In-patient biochemical measures (nadir plasma glucose, peak plasma glucose, hormonal concentrations) are measured from plasma/serum and reported as absolute values, AUC or iAUC as specified. Gastric emptying assessed by acetaminophen (paracetamol) Tmax and Cmax."}

Denmark

Earliest CTIS Part Ii Submission Date

04-10-2024

Latest Decision Or Authorization Date

04-03-2026

Processing Time Days

516

Number Of Sites

1

Number Of Participants

24

Primary sponsor

Full Name

Steno Diabetes Center Copenhagen

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Denmark

Third parties

• {"country":"Denmark","full_name":"Frederiksberg Hospital","duties_or_roles":"Sponsor duties (code: 1); contact email: gcp-enheden.bispebjerg-frederiksberg-hospitaler@regionh.dk","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"","full_name":"Lexicon A/S","duties_or_roles":"Study investigational medical product and placebo are provided by Lexicon A/S (listed as source of investigational product)","organisation_type":""}
• {"country":"","full_name":"Læge Sofus Carl Emil Friis og hustru Olga Doris Friis legat","duties_or_roles":"Source of monetary support (listed under sourceOfMonetarySupport)","organisation_type":""}