title: Novel partial 5HT3 agonist pumosetrag reduces acid reflux events in uninvestigated GERD patients after a standard refluxogenic meal: a randomized, double-blind, placebo-controlled pharmacodynamic study.
abstract: 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 5HT3 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.
  
  
  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
  In GERD, the partial 5HT3 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.
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA; Division of Gastroenterology and Hepatology, Korea University College of Medicine, Korea University, Seoul, South Korea.
authors.forename: R S
authors.initials: RS
authors.lastname: Choung
authors.forename: G R
authors.initials: GR
authors.lastname: Locke
authors.forename: D D
authors.initials: DD
authors.lastname: Francis
authors.forename: D
authors.initials: D
authors.lastname: Katzka
authors.forename: P J
authors.initials: PJ
authors.lastname: Winkle
authors.forename: W C
authors.initials: WC
authors.lastname: Orr
authors.forename: M D
authors.initials: MD
authors.lastname: Crowell
authors.forename: K
authors.initials: K
authors.lastname: Devault
authors.forename: W S
authors.initials: WS
authors.lastname: Harmsen
authors.forename: A R
authors.initials: AR
authors.lastname: Zinsmeister
authors.forename: N J
authors.initials: NJ
authors.lastname: Talley
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D054333:Drug Partial Agonism; D005260:Female; D005764:Gastroesophageal Reflux / Q000188:drug therapy* / Q000503:physiopathology; D006356:Heartburn / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008297:Male; D062407:Meals / Q000502:physiology*; D008875:Middle Aged; D011725:Pyridines / Q000627:therapeutic use*; D011812:Quinuclidines / Q000627:therapeutic use*; D058827:Serotonin 5-HT3 Receptor Agonists / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D011725:Pyridines; D011812:Quinuclidines; D058827:Serotonin 5-HT3 Receptor Agonists; C482040:Pumosetrag
keywords: GERD; Pharmacodynamic study; Pumosetrag