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-oesophageal reflux disease

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 Results: ADX10059 250 mg t.i.d. significantly decreased the percentage of time with pH 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.