title: Randomised clinical trial: effects of monotherapy with ADX10059, a mGluR5 inhibitor, on symptoms and reflux events in patients with gastro-oesophageal reflux disease.
abstract: BACKGROUND
  ADX10059, a metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulator, has been shown to reduce gastro-oesophageal reflux events and oesophageal acid exposure in patients with gastro-oesophageal reflux disease (GERD) and healthy subjects.
  
  
  OBJECTIVE
  To evaluate the effects of ADX10059 monotherapy for 2 weeks on symptom control in patients with GERD.
  
  
  METHODS
  This was a double-blind, placebo-controlled, multi-centre trial in GERD patients who were responders to proton pump inhibitors (PPIs). Following PPIs withdrawal, a 2-week baseline washout period was followed by 2-week treatment with either ADX10059 120 mg or placebo b.d. The primary clinical efficacy endpoint was the number of GERD symptom-free days in treatment week 2 compared with the last 7 days of baseline. The effect on reflux events using 24-h impedance-pH monitoring was also determined in a subset of 24 patients.
  
  
  RESULTS
  The full analysis set comprised 103 patients ADX10059 (N= 50), Placebo (N=53). In treatment week 2, ADX10059 significantly increased GERD symptom-free days (P=0.045) and heartburn-free days (P=0.037), reduced antacid use (P=0.017), improved total symptom score (P=0.048) including subscale heartburn/regurgitation (P=0.007) and sleep disturbance because of GERD (P= 0.022). ADX10059 significantly reduced total (P=0.034) and acidic reflux events (P=0.003). ADX10059 was well tolerated. Most common adverse events for ADX10059 were mild to moderate dizziness 16% and vertigo 12% (placebo 4% and 2%).
  
  
  CONCLUSIONS
  Inhibition of mGluR5 with ADX10059 monotherapy reduces reflux events and improves symptoms in GERD patients. This mechanism has promise for the management of GERD.
authors.affiliation: Gastroenterology Department, CHU Bordeaux, Saint André Hospital, and Université Victor Segalen Bordeaux 2, Bordeaux, France.
authors.forename: F
authors.initials: F
authors.lastname: Zerbib
authors.forename: S
authors.initials: S
authors.lastname: Bruley des Varannes
authors.forename: S
authors.initials: S
authors.lastname: Roman
authors.forename: R
authors.initials: R
authors.lastname: Tutuian
authors.forename: J-P
authors.initials: JP
authors.lastname: Galmiche
authors.forename: F
authors.initials: F
authors.lastname: Mion
authors.forename: J
authors.initials: J
authors.lastname: Tack
authors.forename: P
authors.initials: P
authors.lastname: Malfertheiner
authors.forename: C
authors.initials: C
authors.lastname: Keywood
mesh_terms: D000328:Adult; D000368:Aged; D000494:Allosteric Regulation / Q000187:drug effects; D004311:Double-Blind Method; D050782:Esophageal pH Monitoring; D005260:Female; D005764:Gastroesophageal Reflux / Q000188:drug therapy* / Q000378:metabolism; D006356:Heartburn / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D054328:Proton Pump Inhibitors; D016032:Randomized Controlled Trials as Topic; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
chemical_list: C578935:GRM5 protein, human; D054328:Proton Pump Inhibitors; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate