Pasireotide in dumping syndrome-results from a phase 2, international, multicentre study

Introduction: Dumping syndrome is a prevalent complication of gastric bypass surgery, characterised by early (cardiovascular and gastrointestinal response, along with rise in haematocrit [Ht] and pulse rate [PR]) and late (hypoglycaemia due to excess insulin) postprandial symptoms. Only a subset of patients (pts) responds to treatment based on dietary measures, off-label use of acarbose and somatostatin analogues (SSA). Pasireotide (PAS), a next-generation SSA with high affinity to 4 of the 5 somatostatin receptor subtypes (sst), being a potent inhibitor of incretin and insulin secretion (via sst2 and sst5), prevents postprandial hypoglycaemia. Aims & Methods: This is a single-arm, open-label, multicentre, intra-patient dose escalation, phase 2 study to evaluate the preliminary efficacy, safety and pharmacokinetics of PAS subcutaneous (s.c.) and long-acting release (LAR) in pts with dumping syndrome. The 6-month (mo) core period included a 3-mo s.c. phase followed by a 3-mo LAR phase. Eligible pts started treatment with PAS s.c. 50μg tid (before meals); dose could be increased by increment of 50μg up to 200μg tid based on the presence of hypoglycaemia (plasma glucose75.0%) and 36.4% (12/33; 95% CI: 20.4%>54.9%) in the s.c. and LAR phases, respectively. Notably, plasma glucose levels during OGTT were higher at all time points with s.c. dose vs baseline and vs LAR dose. Fewer pts had an increase in PR of≥10 beat/min and an increase in Ht level of≥3% (from pre-OGTT to 30 min post-OGTT) at mo 3 than at the baseline (18.6% vs 60.5% and 16.3% vs 27.9%, respectively). Overall, the most frequent (>15% of pts [N=43]) AEs were headache (32.6%); diarrhoea, hypoglycaemia (25.6% each); abdominal pain (18.6%); upper abdominal pain and nausea (16.3% each). Grade 3/4 AEs occurred in 32.6% pts; most frequent (≥2 pts) were hypoglycaemia (9.3%); diarrhoea, upper abdominal pain, dizziness and small intestinal obstruction (4.7% each). Conclusion: These results suggest that PAS s.c. effectively controls postprandial hypoglycaemia and improves changes in PR and Ht in pts with dumping syndrome. PAS s.c. and LAR were well tolerated; no new safety signals were identified in this population. A phase 3 study is warranted to confirm the effects of PAS in dumping syndrome.