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Randomized Controlled Trial
. 2021 May;53(9):1010-1020.
doi: 10.1111/apt.16304. Epub 2021 Mar 12.

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

Victor Chedid  1 , Justin Brandler  1 , Kayla Arndt  1 , Priya Vijayvargiya  1 , Xiao Jing Wang  1 , Duane Burton  1 , W Scott Harmsen  1 , Jenifer Siegelman  2 , Chunlin Chen  2 , Yinzhong Chen  2 , Cristina Almansa  2 , George Dukes  2 , Michael Camilleri  1
Affiliations
Randomized Controlled Trial

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

Victor Chedid et al. Aliment Pharmacol Ther. 2021 May.

Abstract

Background: Gastroparesis is defined by delayed gastric emptying with associated symptoms in the absence of mechanical obstruction.

Aim: To evaluate pharmacokinetics and pharmacodynamics of felcisetrag, a highly selective 5-HT4 receptor agonist, on total gut transit in patients with documented delayed gastric emptying of solids.

Methods: Single-centre, placebo-controlled study of 36 participants receiving placebo, 0.1mg, 0.3mg or 1.0mg of felcisetrag I.V. infusion, daily, for 3 days. At baseline, each participant completed a 4h, 99m Tc-egg meal (300 kcal, 30% fat) gastric emptying test. Following infusion (Day 2), gastric, small bowel and colonic transit of solids were measured over 48h (same meal plus 111 In-charcoal delivered in methacrylate-coated capsule). Samples were collected for pharmacokinetics. The primary endpoint was gastric emptying T1/2 . Statistical analysis used baseline parameters as covariates (ANCOVA).

Results: Patients (22 idiopathic, 14 diabetic gastroparesis) were randomised to felcisetrag (0.1 mg, n = 10; 0.3 mg, n = 9; 1.0 mg, n = 7) or placebo (n = 10). Compared to placebo, felcisetrag significantly accelerated gastric emptying T1/2 , colonic filling at 6h, and 10% small bowel transit time (overall P < 0.01; all three doses individually Bonferroni corrected P < 0.05) for all three measurements. Ascending colon emptying (T1/2 ) was significantly accelerated (all doses), and colonic transit at 48 hours was accelerated with 0.1 mg and 0.3 mg felcisetrag compared to placebo. Pharmacokinetic results were dose proportional. Felcisetrag was well tolerated with no clinically significant findings from clinical laboratory, vital signs or ECG.

Conclusion: I.V. felcisetrag significantly accelerated gastric, small bowel and colonic transit in patients with gastroparesis, and should be further evaluated for short-term treatment of gastric and intestinal motility disorders. ClinicalTrials.gov #NCT03281577.

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Figures

FIGURE 1
FIGURE 1
Study design
FIGURE 2
FIGURE 2
CONSORT flow diagram
FIGURE 3
FIGURE 3
Effects of felcisetrag (0.1 mg, 0.3 mg, 1.0 mg) and placebo on GE T1/2 at baseline and Day 2, and percent change in GE T1/2 from baseline GE T1/2 = gastric half‐emptying time
FIGURE 4
FIGURE 4
Gastric emptying of solids (% emptied) over time in patients with diabetic or idiopathic gastroparesis based on treatment group on Day 2 of placebo or increasing doses of felcisetrag; data show mean at each time point
FIGURE 5
FIGURE 5
Small bowel transit time 10% in patients with diabetic or idiopathic gastroparesis based on treatment group on Day 2 of placebo or increasing doses of felcisetrag; data show median, IQR, time point
FIGURE 6
FIGURE 6
Progression of colonic geometric centre over time in patients with diabetic or idiopathic gastroparesis based on treatment group after 48 hours of placebo or increasing doses of felcisetrag; data show mean at each time point for the different treatment groups
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References

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