Endocrine Abstracts

JOINT1341

Introduction: Post-bariatric hypoglycaemia (PBH) complicates up to 38% and 12% of gastric bypass and vertical sleeve gastrectomy surgeries, respectively. PBH, characterised by postprandial hyperinsulinaemic hypoglycaemic episodes in association with neuroglycopenic symptoms, is caused by rapid gastric emptying and excessive secretion of glucagon-like peptide 1 (GLP-1) and insulin. There are no approved medical therapies; affected patients suffer extreme disability. Pasireotide, a somatostatin receptor ligand, binds with high affinity to somatostatin receptor subtype 5, inhibiting GLP-1 and insulin secretion and slowing gastric emptying. PASIPHY, a Phase II dose-finding study (NCT05928390), will assess pasireotide efficacy and safety in patients with PBH.

Methods: ~72 patients with PBH (age ≥18 years; bariatric surgery ≥6 months prior) will enrol across ~25 sites (Europe/USA). The study comprises a ≤3-week (W) screening, a 4W run-in and a 12W randomised, double-blind, placebo-controlled treatment period. Patients with ≥4 postprandial hypoglycaemic events (self-monitored blood glucose [SMBG] <54 mg/dL [<3. 0 mmol/l], a neuroglycopenia event or a level 3 hypoglycaemic event) during the run-in period are randomly allocated to subcutaneous pasireotide at doses of 50, 100 or 200 μg 3 times a day (tid) or matching placebo (3:1 ratio). All patients initiate treatment with 50 μg pasireotide; dose increases occur on days 5 (to 100 μg) and 9 (to 200 μg). Those completing the 12W core phase can choose to receive pasireotide during a 36W open-label extension. All patients will start the extension on pasireotide 50 μg tid; dose can be adjusted for safety/efficacy reasons (up to 200 μg). The primary endpoint is change in blood glucose levels measured by peak:nadir glucose area under the curve during the mixed-meal tolerance test (MMTT) from baseline to W12 of treatment. Core-phase secondary endpoints (assessed at W4, W8 and W12, unless otherwise specified) include: change from baseline in rate of level 2 hypoglycaemic events; change from baseline in rate of level 3 hypoglycaemic events; duration of level 2 hypoglycaemic events; change from baseline in frequency of rescue therapy use; change from baseline to W12 in insulin, glucagon and GLP-1 secretion during MMTT; change from baseline to W12 in health-related quality of life; and incidence of adverse events throughout the study. These endpoints and others will be assessed throughout the extension.

Conclusion: PASIPHY will provide valuable data on pasireotide efficacy and safety, ascertain which dose has the best benefit:risk ratio, and determine whether it is a viable treatment option for patients with PBH.