Felcisetrag shows therapeutic potential in gastric, intestinal motility disorders

Treatment with the highly selective 5‐HT₄ receptor agonist felcisetrag appears to significantly speed up gastric, small bowel, and colonic transit in patients with gastroparesis, as shown in a study.

The study randomized 36 participants (22 idiopathic, 14 diabetic gastroparesis) to receive placebo or felcisetrag at 0.1, 0.3, or 1.0 mg. Treatment was administered as an intravenous infusion daily for 3 days.

Every participant completed a 4h, ^99mTc‐egg meal (300 kcal, 30 percent fat) gastric emptying test at baseline. Following infusion (day 2), gastric, small bowel, and colonic transit of solids were measured over 48 hours (same meal plus ¹¹¹In‐charcoal delivered in methacrylate‐coated capsule).

Relative to placebo, felcisetrag significantly accelerated gastric emptying T_1/2, colonic filling at 6 hours and 10-percent small bowel transit time (overall, p<0.01; all three doses individually, p<0.05) for all three measurements.

Furthermore, ascending colon emptying (T_1/2) went faster with all felcisetrag doses, while colonic transit at 48 hours sped up with the 0.1- and 0.3-mg doses versus placebo. Pharmacokinetic results were dose proportional.

Felcisetrag was well tolerated with no significant findings from clinical laboratory, vital signs, or ECG. None of the patients died, but one withdrew treatment due to poor intravenous access and the other due to a serious adverse event (mild elevated pancreatic enzymes without evidence of pancreatitis; not drug related). Adverse events, such as diarrhoea and nausea, were mostly mild or moderate, and frequency was generally comparable between felcisetrag doses and placebo.

The findings support further evaluation of felcisetrag for short‐term treatment of gastric and intestinal motility disorders.