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Novel partial 5 HT 3 agonist pumosetrag reduces acid reflux events in uninvestigated GERD patients after a standard refluxogenic meal: a randomized, double‐blind, placebo‐controlled pharmacodynamic study
Author(s) -
Choung R. S.,
Locke G. R.,
Francis D. D.,
Katzka D.,
Winkle P. J.,
Orr W. C.,
Crowell M. D.,
DeVault K.,
Harmsen W. S.,
Zinsmeister A. R.,
Talley N. J.
Publication year - 2014
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.12214
Subject(s) - gerd , heartburn , gastroenterology , reflux , placebo , medicine , meal , disease , alternative medicine , pathology
Background Low basal lower esophageal sphincter ( LES ) pressure and transient LES relaxations are major causes of gastroesophageal reflux disease ( GERD ). Pumosetrag, a novel selective partial 5 HT 3 receptor agonist, showed a promising effect on reducing reflux events in health. We aimed to evaluate the effect of pumosetrag on changes in reflux episodes, lower esophageal sphincter pressure ( LESP ), and specific symptoms in patients with GERD receiving a refluxogenic meal. Methods Patients with GERD , who developed heartburn and/or regurgitation after ingestion of a refluxogenic meal, were randomized to 1 of 3 dose levels of pumosetrag (0.2, 0.5, or 0.8 mg) or placebo. Before and after 7 days of treatment, patients underwent manometry, intraesophageal multichannel, intraluminal impedance and pH after a standard refluxogenic meal. Key Results A total of 223 patients with GERD [125 (56%) women, mean (SD) age = 36 (12) years] were enrolled. No overall treatment effects were detected for the total number of reflux episodes (acidic and weakly acidic) (p > 0.5); however, significant treatment effects (p < 0.05) on the number of acid reflux episodes were observed with lower values on pumosetrag 0.2 mg (10.8 ± 1.1), 0.5 mg (9.5 ± 1.1), and 0.8 mg (9.9 ± 1.1) compared with placebo (13.3 ± 1.1). Significant treatment effects (p < 0.05) were also observed for the percentage of time pH was <4, with less time for pumosetrag at 0.5 mg (10%) and 0.8 mg (10%) compared with placebo (16%). Conclusions & Inferences In GERD , the partial 5 HT 3 agonist pumosetrag significantly reduced the rate of acid reflux events but did not result in a significant change in LESP or symptomatic improvement over a 1‐week treatment period.