A randomized phase 2 study of the 5-HT 4 receptor agonist felcisetrag for postoperative gastrointestinal dysfunction after bowel surgery.

Background: Felcisetrag (5-hydroxytryptamine-4 receptor [5-HT ₄ ] agonist) is under investigation as prophylaxis or active treatment for accelerating resolution of gastrointestinal function post-surgery.
Methods: Phase 2, randomized, placebo-controlled, parallel five-arm, double-blind, multicenter study (NCT03827655) in 209 adults undergoing open or laparoscopic-assisted bowel surgery. Patients received intravenous placebo, felcisetrag 0.1 mg/100 ​mL or 0.5 mg/100 ​mL pre-surgery only, or pre-surgery and daily post-surgery until return of gastrointestinal function or for up to 10 days.
Primary Endpoint: time to recovery of gastrointestinal function.
Results: Median time to recovery of gastrointestinal function was 2.6 days for both felcisetrag 0.5 ​mg daily and 0.5 ​mg pre-surgery versus 1.9 days for placebo (p ​> ​0.05). There were no notable differences in adverse events between treatment arms.
Conclusions: Felcisetrag was well tolerated with no new safety concerns. However, no clinically meaningful difference in time to recovery of gastrointestinal function versus placebo was observed. Further investigation of the utility of 5-HT ₄ agonists in complicated, open abdominal surgeries may be warranted.
Competing Interests: Declaration of competing interest GB has received a research grant from Takeda and is an Editorial Board Member for Gut. SA has nothing to declare. ME has nothing to declare. GD was an employee of Takeda Development Center Americas, Inc. and received stock or stock options at the time of the study; they are currently an employee of Ironwood Pharmaceuticals, Inc. RG, PK, JT, PT, JW, and YZ are employees of Takeda Development Center Americas, Inc. and receive stock or stock options. PRW was an employee of Takeda Development Center Americas, Inc. and received stock or stock options at the time of the study; he is currently the founding principal at Second Brain Consulting, LLC, Philadelphia, PA, USA.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)