title: Arbaclofen placarbil in GERD: a randomized, double-blind, placebo-controlled study.
abstract: OBJECTIVE
  It has been shown that arbaclofen placarbil (AP) inhibits reflux in gastroesophageal reflux disease (GERD) following single oral dosing. This study evaluated the efficacy and safety of AP over 4 weeks in subjects with symptomatic GERD.
  
  
  METHODS
  One hundred fifty-six subjects with heartburn and/or regurgitation ≥3 days/week and either no history of taking proton pump inhibitors (PPIs naive, n=58) or at least partial symptom response to PPI therapy (PPI responsive, n=98) were enrolled in this randomized, double-blind, placebo-controlled trial. All GERD therapies including PPIs were discontinued 2 weeks before randomization to AP 20, 40, or 60 mg daily, 30 mg twice daily, or placebo for 4 weeks. Randomization was stratified by prior PPI use.
  
  
  RESULTS
  In the primary analysis, change from baseline in weekly heartburn events between AP and placebo for the entire study group was not statistically significant. However, a significant interaction was observed between prior PPI use and response to AP treatment. In pre-planned secondary analyses of the PPI-responsive subgroup, percent reductions from baseline in weekly heartburn events were greater for each AP dose vs. placebo (P<0.05) and the percentage of subjects who reported complete resolution of heartburn during week 4 was higher in each AP treatment group (21, 28, 30, and 50% for AP 20, 40, 60 mg daily, and 30 mg twice daily, respectively) compared with placebo (6%) (P<0.05 for 30 mg twice daily). Corresponding analyses of the PPI-naive subgroup showed no significant differences. AP was well tolerated; withdrawals due to adverse events were infrequent.
  
  
  CONCLUSIONS
  AP was not superior to placebo in reducing the number of weekly heartburn events over 4 weeks in the primary analysis of the entire study population. Exploratory subgroup analyses suggest that response to PPI treatment before the study was associated with a response to AP treatment.
authors.affiliation: University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53066, USA. nvakil@wisc.edu
authors.forename: Nimish B
authors.initials: NB
authors.lastname: Vakil
authors.forename: F Jacob
authors.initials: FJ
authors.lastname: Huff
authors.forename: Amy
authors.initials: A
authors.lastname: Bian
authors.forename: Drew S
authors.initials: DS
authors.lastname: Jones
authors.forename: David
authors.initials: D
authors.lastname: Stamler
mesh_terms: D000328:Adult; D000368:Aged; D001418:Baclofen / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004244:Dizziness / Q000139:chemically induced; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005764:Gastroesophageal Reflux / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D006261:Headache / Q000139:chemically induced; D006356:Heartburn / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009125:Muscle Relaxants, Central / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D009325:Nausea / Q000139:chemically induced; D011355:Prodrugs / Q000627:therapeutic use; D054328:Proton Pump Inhibitors / Q000627:therapeutic use; D017211:Treatment Failure
chemical_list: D009125:Muscle Relaxants, Central; D011355:Prodrugs; D054328:Proton Pump Inhibitors; D001418:Baclofen; C543531:arbaclofen placarbil