Randomised clinical trial: effects of monotherapy with ADX10059, a mGluR5 inhibitor, on symptoms and reflux events in patients with gastro-oesophageal reflux disease

P>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. Aim 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 (ClinicalTrials.gov, number NCT00820079).