Gut doi:10.1136/gut.2008.162040

A Proof Of Concept Study Evaluating The Effect Of ADX10059, A Metabotropic Glutamate Receptor-5 Negative Allosteric Modulator, On Acid Exposure And Symptoms In Gastro-Esophageal Reflux Disease

  1. Charlotte Keywood (charlotte.keywood{at}
  1. Addex Pharma, Switzerland
    1. Mark Wakefield (mark.wakefield{at}
    1. Addex Pharma, Switzerland
      1. Jan Tack (jan.tack{at}
      1. University of Leuven, Belgium
        • Published Online First 20 May 2009


        Background: In preclinical models, antagonism of metabotropic glutamate receptor 5 (mGluR5) reduces transient lower esophageal sphincter relaxations (TLESRs) and increases LES pressure. This study evaluated the effect of ADX10059, a potent, selective, negative allosteric modulator (NAM) of mGluR5, on esophageal pH-metry and clinical symptoms in GERD.

        Methods: Two groups of GERD patients (N=12 per group) underwent 24-hour esophageal pH-metry on 2 sequential treatment days. The patients received oral placebo t.i.d. 30 min before a high fat meal on Day 1 and oral ADX10059 50 mg (Group 1) or 250 mg (Group 2) t.i.d. 30 min before a high fat meal on Day 2. The primary variable was acid exposure (%time pH<4). Secondary variables included number and duration of reflux episodes, number and duration of symptomatic episodes and symptoms recorded in diaries. Comparisons were made for Day 2 (active) versus Day 1 (placebo) treatment and for Group 1 versus Group 2.

        Results: ADX10059 250 mg t.i.d. significantly decreased the percentage of time with pH<4 from 7.2% to 3.6% (p=0.01). ADX10059 250 mg t.i.d. reduced pH-metry measured esophageal acid exposure, throughout the 24-hour period, nocturnally and postprandially and significantly reduced the number and duration of symptomatic reflux episodes (p=0.03). ADX10059 50 mg t.i.d. was not significantly superior to placebo. ADX10059 was generally well tolerated.

        Conclusion: The mGluR5 NAM ADX10059 reduced acid reflux which was associated with improvement in clinical symptoms in GERD patients. ADX10059 appears to have a potential role in clinical management of GERD.

        Free sample
        This recent issue is free to all users to allow everyone the opportunity to see the full scope and typical content of Gut.
        View free sample issue >>

        Don't forget to sign up for content alerts so you keep up to date with all the articles as they are published.

        Navigate This Article