TY - JOUR
T1 - Randomised study
T2 - effects of the 5-HT4 receptor agonist felcisetrag vs placebo on gut transit in patients with gastroparesis
AU - Chedid, Victor
AU - Brandler, Justin
AU - Arndt, Kayla
AU - Vijayvargiya, Priya
AU - Wang, Xiao Jing
AU - Burton, Duane
AU - Harmsen, W. Scott
AU - Siegelman, Jenifer
AU - Chen, Chunlin
AU - Chen, Yinzhong
AU - Almansa, Cristina
AU - Dukes, George
AU - Camilleri, Michael
N1 - Funding Information:
: Michael Camilleri is funded for single‐centre research studies by Allergan and Takeda. He serves as an advisor to Allergan, Takeda, Ironwood with compensation paid to his employer, Mayo Clinic. The other authors have no conflicts of interest. Drs. Cristina Almansa, Jenifer Siegelman, Chunlin Chen, Yinzhong Chen and George Dukes were all employees of Takeda Pharmaceuticals at the time of this research. Dr. Almansa is currently an employee of Ironwood Pharmaceuticals, Dr. Chunlin Chen is currently an employee of Bayer, and Dr. Yinzhong Chen is currently an employee of Radius Health. Declaration of personal interests
Funding Information:
This study was funded by research grant TAK-954-2003 from Takeda Pharmaceuticals International Co., Cambridge, MA, USA. Dr. Camilleri’s studies on gastroparesis are funded by NIH R01-DK122280 grant. The authors thank Mrs. Cindy Stanislav for excellent secretarial assistance. Declaration of personal interests: Michael Camilleri is funded for single-centre research studies by Allergan and Takeda. He serves as an advisor to Allergan, Takeda, Ironwood with compensation paid to his employer, Mayo Clinic. The other authors have no conflicts of interest. Drs. Cristina Almansa, Jenifer Siegelman, Chunlin Chen, Yinzhong Chen and George Dukes were all employees of Takeda Pharmaceuticals at the time of this research. Dr. Almansa is currently an employee of Ironwood Pharmaceuticals, Dr. Chunlin Chen is currently an employee of Bayer, and Dr. Yinzhong Chen is currently an employee of Radius Health.
Funding Information:
This study was funded by research grant TAK‐954‐2003 from Takeda Pharmaceuticals International Co., Cambridge, MA, USA. Dr. Camilleri’s studies on gastroparesis are funded by NIH R01‐DK122280 grant.
Publisher Copyright:
© 2021 Mayo Foundation for Medical and Research. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.
PY - 2021/5
Y1 - 2021/5
N2 - 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, 99mTc-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 111In-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.
AB - 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, 99mTc-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 111In-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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U2 - 10.1111/apt.16304
DO - 10.1111/apt.16304
M3 - Article
C2 - 33711180
AN - SCOPUS:85102655100
SN - 0269-2813
VL - 53
SP - 1010
EP - 1020
JO - Alimentary Pharmacology and Therapeutics
JF - Alimentary Pharmacology and Therapeutics
IS - 9
ER -