A Double-blind Randomized Placebo-controlled Dose-finding Phase II Study to Assess the Efficacy and Safety of Pasireotide s.c. in Patients With Post-Bariatric Hypoglycaemia

SOM230-RECAG-CL-0576

The Total duration of trial participation for each participant with post-bariatric hypoglycemia will be a maximum of 59 weeks, with the following duration of trial periods * 19 weeks for the Core Phase. It is composed of: * a Screening period: a maximum of 3 weeks * a Run-in period (no treatment): 4 weeks * a Blinded Treatment Phase: 12 weeks * 36 weeks Extension Phase = an open-label Treatment period * 4 weeks for the safety follow-up period (without any treatment).

2024-01-04

2025-04-01

2026-04-01

Recruiting

Early phase I

72

Inclusion Criteria: 1. Male or- non-pregnant female patients ≥ 18 years of age 2. Patients able to provide and have provided signed written informed consent prior to study participation. 3. Patients capable of self-injecting subcutaneously. Specific training to self-inject the study drug will be provided. 4. Post-bariatric surgery more than 6 months prior to screening 5. Patient with a documented diagnosis of Post-Bariatric Hypoglycaemia (PBH) defined as having: * postprandial neuroglycopenia occurring \>1 hour after meals * no hypoglycaemia in fasting conditions * documented history of hypoglycaemia based on * glucose value \<50mg/dL or 2.8 mmol/L on a sporadic or scheduled blood analysis - OR - * glucose value \<60 mg/dL or 3.3 mmol/L at 90, 120, 150 or 180 min during an OGTT (Oral Glucose Tolerance Test) - OR- * glucose value \<54 mg/dL at 60, 90, 120 or 180 min during a 3-hour MMTT (Mixed Meal Tolerance Test) 6. Patients must have at least one glucose level \< 54 mg/dL at 30, 90, 120, 150 or 180 min during the 3-hour MMTT at screening 7. Historical evidence of previous level 3 hypoglycaemia events at any time 8. Patients who have failed diet recommended by the treating physician for the PBH 9. Karnofsky Performance Status ≥ 60 (i.e., requires occasional assistance, but is able to care for most of their personal needs) 10. Patients who received other therapies for PBH (such as acarbose, gama guar, pectin, diazoxide) must have stopped all treatments and allow a wash out period of at least 2 weeks prior to entering the run-in period. 11. Patients who have been treated with Glucagon Like Peptide-1 (GLP-1) antagonists in the past must have a wash-out period of at least 4 weeks before the start of the run-in period 12. Patients who have been treated with Sodium-Glucose Transport Protein 2 (SGLT2) inhibitors (glifozins) in the past must have a wash-out period of at least 4 weeks before the start of the run-in period 13. Patients who have been treated with somatostatin receptor analogues in the past, must have an appropriate interval between the last administration of somatostatin receptor analogues treatment and the start of the run-in period as follows: * Octreotide s.c. for ≥ 72 hours * Octreotide LAR for ≥ 56 days (8 weeks) * Lanreotide Autogel for ≥ 98 days (14 weeks) * Lanreotide SR ≥ 28 days (4 weeks) Exclusion Criteria (main ones): 1. Bariatric patients who have lap band. 2. Patients with a current diagnosis of uncontrolled Diabetes Mellitus. However, diabetic patients in remission, as defined below, are eligible: * With an HbA1c at screening \<6.5% * Not taking any medications for hyperglycaemia for at least 3 months prior to screening. * Their qualifying Level 3 hypoglycaemia events (see above) must have occurred at least 1 month after the discontinuation of the glucose lowering agent(s). 3. Patients previously treated with pasireotide at any time 4. Patients who have a known hypersensitivity to somatostatin receptor analogues. 5. Patients currently using medications that may interfere with glucose metabolism within 5 half-lives of drug. 6. Patients with history of or current insulinoma 7. Patients who have any severe and/or uncontrolled medical condition or other conditions that could affect their participation in the study (defined in the core text of the protocol) 8. Patients with symptomatic cholelithiasis and/ or acute or chronic pancreatitis. 9. Patients with abnormal coagulation (PT and PTT elevated by 30% above normal limits). 10. Patients on continuous anticoagulation therapy. Patients who were on anticoagulant therapy must complete a washout period of at least 10 days and have confirmed normal coagulation parameters before study inclusion (patients receiving aspirin once a day are allowed to be enrolled). 11. Patients who are hypothyroid and not on adequate replacement therapy. 12. Patients who have undergone major surgery/surgical therapy for any cause within 1 month. Patients should have recovered from the surgery and be in good clinical condition before entering the study. 13. Bradycardia and QT-related exclusion criteria (in the core text of the protocol) 14. Participation in any clinical investigation within 4 weeks prior to dosing or longer if required by local regulation. (Use of an investigational drug within 1 month prior to dosing). 15. Significant acute illness within the two weeks prior to dosing/randomization. 16. Female patients who are pregnant, intending to become pregnant or breastfeed during the study or lactating, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test. 17. Women of childbearing potential (WOCBP) who are unwilling of using highly effective contraception methods (definition in core protocol) 18. Potentially unreliable or vulnerable patients (e.g., person kept in detention) and those judged by the investigator to be unsuitable for the study.

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2024-04-23