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Gut. 2009 Sep;58(9):1192-9. doi: 10.1136/gut.2008.162040. Epub 2009 May 20.

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.

Author information

  • 1Addex Pharma SA, Plan-les-Ouates, CH-1228 Switzerland. charlotte.keywood@addexpharma.com

Abstract

BACKGROUND:

In preclinical models, antagonism of metabotropic glutamate receptor 5 (mGluR5) reduces transient lower oesophageal sphincter relaxations (TLOSRs) and increases LOS pressure. This study evaluated the effect of ADX10059, a potent, selective, negative allosteric modulator of mGluR5, on oesophageal pH-metry and clinical symptoms in GORD.

METHODS:

Two groups of patients with GORD (n = 12 per group) underwent 24-h oesophageal pH-metry on two sequential treatment days. The patients received oral placebo three times daily (tds) 30 min before a high-fat meal on Day 1 and oral ADX10059 50 mg (Group 1) or 250 mg (Group 2) tds 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 tds significantly decreased the percentage of time with pH<4 from 7.2% to 3.6% (p = 0.01). ADX10059 250 mg tds reduced pH-metry-measured oesophageal acid exposure, throughout the 24 h period, nocturnally and postprandially, and significantly reduced the number and duration of symptomatic reflux episodes (p = 0.03). ADX10059 50 mg tds was not significantly superior to placebo. ADX10059 was generally well tolerated.

CONCLUSION:

The mGluR5 negative allosteric modulator ADX10059 reduced acid reflux which was associated with improvement in clinical symptoms in patients with GORD. ADX10059 appears to have a potential role in the clinical management of GORD.

PMID:
19460767
[PubMed - indexed for MEDLINE]
PMCID:
PMC2719084
Free PMC Article

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