Sotagliflozin for the treatment of post-bariatric hypoglycaemia: The ONSIDE study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Steno Diabetes Center Copenhagen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

3 Nov 2025 → ongoing

Decision date (initial)

2024-10-14

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Study investigational medical product and placebo are provided by Lexicon A/S · Læge Sofus Carl Emil Friis og hustru Olga Doris Friis legat

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

We aim to investigate the effect of sotagliflozin on hypoglycaemia and glycaemic excursions in an interventional randomized, double-blind, placebo-controlled crossover study in RYGB-operated persons suffering from confirmed biochemical post-bariatric hypoglycaemia. Participants will undergo the following two interventions in random order for periods of four weeks: sotagliflozin 400 mg QD and placebo.

Conditions and MedDRA coding

Postbariatric hypoglycaemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Age 18-74 years
2. RYGB-operation conducted >18 months ago
3. History of postprandial neuroglycopenia one–to–three hours after meal intake with subsequent relief after carbohydrate ingestion (per interview)
4. 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
5. Haemoglobin levels for women >7.3 mmol/l and for men > 8.3 mmol/l
6. Fasting plasma glucose concentration >3.5 mmol/l
7. Sinus rhythm at screening and no medical history of cardiac arrhythmias or cardiac ischaemia
8. Negative urine human chorionic gonadotropin (hCG) (for fertile women)

Exclusion criteria 11

1. Treatment with medication(s) affecting insulin secretion, glucose metabolism, or any antidiabetic drugs
2. History of ketoacidosis
3. History of chronic kidney disease or an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2
4. Current participation in another clinical trial with administration of an investigational drug
5. Pregnancy or breastfeeding
6. Glycated haemoglobin (HbA1c) ≥48 mmol/mol
7. Major surgery within 30 days before screening
8. Alcohol abuse (per investigator assessment)
9. 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
10. History of hypersensitivity or allergic reaction to sotagliflozin or any of the excipients
11. Known or suspected allergies to SGLT-2 inhibitors or related products

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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)

Secondary endpoints 25

1. Time (% or minutes/per day) in level 1 hypoglycaemia (IG 3.0–3.9 mmol/l) (out-patient part)
2. Time (% or minutes/per day) below range (IG < 3.9 mmol/l, including readings <3.0 mmol/l) (out-patient part)
3. Time (% or minutes/per day) in range (IG 3.9–10.0 mmol/l) (out-patient part)
4. Time (% or minutes/per day) above tight range (>7.8 mmol/l) (out-patient part)
5. Time (% or minutes/per day) above range (>10.0 mmol/l) (out-patient part)
6. Time (% or minutes/per day) above range (>13.9 mmol/l) (out-patient part)
7. Frequency (no of events/day) of hypoglycaemic events (IG < 3.9 mmol/l, ≥15 min) (out-patient part)
8. Frequency (no of events/day) of level 1 hypoglycaemic events (IG 3.0–3.9 mmol/l, ≥15 min) (out-patient part)
9. Frequency (no of events/day) of level 2 hypoglycaemic events (IG <3.0 mmol/l, ≥15 min) (out-patient part)
10. Frequency (no of events/day) of hyperglycaemic events (>10.0 mmol/l, ≥15 min) (out-patient part)
11. Glycaemic variability assessed as coefficient of variation (CV) (out-patient part)
12. Glycaemic variability assessed as standard deviation (SD) (out-patient part)
13. Glycaemic variability assessed as low blood glucose index (LBGI) (out-patient part)
14. Change in full score of Edinburgh Hypoglycaemia Symptom scale during treatment (EHSS) (out-patient part)
15. Change in full score of fear of hypoglycaemia as assessed by Hypoglycaemia Fear Scale (HFS-II) (out-patient part)
16. Change in full score of quality of life as assessed by the 36-item Short Form health survey (SF-36) (out-patient part)
17. Nadir plasma glucose assessed as the absolute lowest value (in-patient part)
18. Time spent in hypoglycaemia (<3.9 mmol/l) (in-patient part)
19. Time spent in level 1 and level 2 hypoglycaemia (3.0–3.9 and < 3.0 mmol/l, respectively) (in-patient part)
20. Change in full score of Edinburgh Hypoglycemia Symptom scale (in-patient part)
21. Glycaemic rescue intervention due to critically low plasma glucose concentration (≤ 1.8 mmol/l) or onset of marked neuroglycopenic symptoms (in-patient part)
22. Time spent in hyperglycaemia (>7.8, >10.0 and 13.9 mmol/l, respectively) (in-patient part)
23. Peak plasma glucose concentration (in-patient part)
24. 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)
25. Rate of gastric emptying as assessed by acetaminophen concentration (paracetamol): Tmax and Cmax (in-patient part)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Steno Diabetes Center Copenhagen

Sponsor organisation

Steno Diabetes Center Copenhagen

Address

Borgmester Ib Juuls Vej 83

City

Herlev

Postcode

2730

Country

Denmark

Scientific contact point

Organisation

Steno Diabetes Center Copenhagen

Contact name

Andreas Andersen

Public contact point

Organisation

Steno Diabetes Center Copenhagen

Contact name

Andreas Andersen

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications