Randomised study: effects of the 5‐HT₄ receptor agonist felcisetrag vs placebo on gut transit in patients with gastroparesis

Summary Background Gastroparesis is defined by delayed gastric emptying with associated symptoms in the absence of mechanical obstruction. Aim To evaluate pharmacokinetics and pharmacodynamics felcisetrag, a highly selective 5‐HT 4 receptor agonist, on total gut transit patients documented solids. Methods Single‐centre, placebo‐controlled study 36 participants receiving placebo, 0.1mg, 0.3mg or 1.0mg felcisetrag I.V. infusion, daily, for 3 days. At baseline, each participant completed 4h, 99m Tc‐egg meal (300 kcal, 30% fat) test. Following infusion (Day 2), gastric, small bowel colonic solids were measured over 48h (same plus 111 In‐charcoal delivered methacrylate‐coated capsule). Samples collected pharmacokinetics. The primary endpoint was T 1/2 . Statistical analysis used baseline parameters as covariates (ANCOVA). Results Patients (22 idiopathic, 14 diabetic gastroparesis) randomised to (0.1 mg, n = 10; 0.3 9; 1.0 7) placebo (n 10). Compared significantly accelerated , filling at 6h, 10% time (overall P < 0.01; all three doses individually Bonferroni corrected 0.05) measurements. Ascending colon ( ) (all doses), 48 hours 0.1 mg compared placebo. Pharmacokinetic results dose proportional. Felcisetrag well tolerated no clinically significant findings from clinical laboratory, vital signs ECG. Conclusion gastroparesis, should be further evaluated short‐term treatment intestinal motility disorders. ClinicalTrials.gov #NCT03281577