title: A novel reflux inhibitor lesogaberan (AZD3355) as add-on treatment in patients with GORD with persistent reflux symptoms despite proton pump inhibitor therapy: a randomised placebo-controlled trial.
abstract: OBJECTIVE
  o evaluate the efficacy and tolerability of add-on treatment with lesogaberan (AZD3355), a novel reflux inhibitor, in patients with persistent gastro-oesophageal reflux disease (GORD) symptoms despite proton pump inhibitor (PPI) therapy.
  
  
  METHODS
  double-blind, placebo-controlled, randomised, parallel-group, multicentre phase IIA study was carried out in outpatient clinics. The study group comprised 244 adult patients with persistent GORD symptoms (heartburn and/or regurgitation) of at least mild intensity and for 3 days of 7 days before enrolment, despite ≥6 weeks of continuous PPI therapy. Patients received either lesogaberan (65 mg twice daily) or placebo in addition to PPI therapy for a period of 4 weeks. Symptom intensity, based on the Reflux Disease Questionnaire, was recorded twice daily. Treatment response (defined as at most one 24 h period with heartburn or regurgitation of not more than mild intensity during the last 7 days of treatment). Time to response, proportion of symptom-free days and measures of tolerability were also analysed.
  
  
  RESULTS
  total of 232 (114 lesogaberan- and 118 placebo-treated patients) of the 244 randomised patients were analysed for efficacy. Treatment with lesogaberan, compared with placebo, resulted in a significantly larger proportion of responders to treatment (16% vs 8% of patients; p=0.026) and cumulative proportion of responders over time (log-rank p=0.0195). Lesogaberan was well tolerated: adverse events of mostly mild to moderate intensity were reported in 45% of patients on lesogaberan and in 37% on placebo.
  
  
  CONCLUSIONS
  esogaberan add-on therapy to PPIs significantly improved heartburn and regurgitation symptoms; however, the proportion of responders was small. Clinical trial number NCT00394472.
authors.affiliation: Department of Gastroenterology, University Hospital Leuven, Catholic University of Leuven, Herestraat 49, 3000 Leuven, Belgium. uy.boeckxstaens@med.kuleuven.be
authors.forename: Guy E
authors.initials: GE
authors.lastname: Boeckxstaens
authors.forename: Hanneke
authors.initials: H
authors.lastname: Beaumont
authors.forename: Jan G
authors.initials: JG
authors.lastname: Hatlebakk
authors.forename: Debra G
authors.initials: DG
authors.lastname: Silberg
authors.forename: Karin
authors.initials: K
authors.lastname: Björck
authors.forename: Maria
authors.initials: M
authors.lastname: Karlsson
authors.forename: Hans
authors.initials: H
authors.lastname: Denison
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004812:Epidemiologic Methods; D005260:Female; D058785:GABA-A Receptor Agonists / Q000008:administration & dosage / Q000627:therapeutic use; D005764:Gastroesophageal Reflux / Q000188:drug therapy*; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010721:Phosphinic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011437:Propylamines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D058785:GABA-A Receptor Agonists; D005765:Gastrointestinal Agents; D010721:Phosphinic Acids; D011437:Propylamines; D054328:Proton Pump Inhibitors; C545087:lesogaberan