{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T03:44:02Z","timestamp":1772163842215,"version":"3.50.1"},"reference-count":24,"publisher":"BMJ","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"accepted":{"date-parts":[[2012,5,25]]},"published-print":{"date-parts":[[2013,9]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Lesogaberan (AZD3355) is a novel \u03b3-aminobutyric acid B-type receptor agonist designed to treat gastro-oesophageal reflux disease (GERD) by inhibiting transient lower oesophageal sphincter relaxations. A randomised, double-blind, placebo-controlled, multi-centre phase IIb study was performed to assess the efficacy and safety of lesogaberan as an add-on to proton pump inhibitor (PPI) therapy in patients with GERD who are partially responsive to PPI therapy (ClinicalTrials.gov reference:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT01005251\">NCT01005251<\/jats:ext-link>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>In total, 661 patients were randomised to receive 4\u2005weeks of placebo or 60, 120, 180 or 240\u2005mg of lesogaberan twice daily, in addition to ongoing PPI therapy. Symptoms were measured using the Reflux Symptom Questionnaire electronic Diary. Response to treatment was defined as having an average of \u22653 additional days per week of not more than mild GERD symptoms during treatment compared with baseline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the primary analysis, 20.9%, 25.6%, 23.5% and 26.2% of patients responded to the 60, 120, 180 and 240\u2005mg twice daily lesogaberan doses, respectively, and 17.9% responded to placebo. The response to the 240\u2005mg twice daily dose was statistically significantly greater than the response to placebo using a one-sided test at the predefined significance level of p&lt;0.1. However, the absolute increases in the proportions of patients who responded to lesogaberan compared with placebo were low. Lesogaberan was generally well tolerated, although six patients receiving lesogaberan developed reversible elevated alanine transaminase levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In patients with GERD symptoms partially responsive to PPI therapy, lesogaberan was only marginally superior to placebo in achieving an improvement in symptoms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/gutjnl-2012-302737","type":"journal-article","created":{"date-parts":[[2012,6,23]],"date-time":"2012-06-23T20:54:47Z","timestamp":1340484887000},"page":"1248-1255","source":"Crossref","is-referenced-by-count":50,"title":["Efficacy and safety of lesogaberan in gastro-oesophageal reflux disease: a randomised controlled trial"],"prefix":"10.1136","volume":"62","clinical-trial-number":[{"clinical-trial-number":"nct01005251","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01005251","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct00703534","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Nicholas J","family":"Shaheen","sequence":"first","affiliation":[{"name":"Center for Esophageal Diseases and Swallowing, Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans","family":"Denison","sequence":"additional","affiliation":[{"name":"AstraZeneca R&D, M\u00f6lndal, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Bj\u00f6rck","sequence":"additional","affiliation":[{"name":"AstraZeneca R&D, M\u00f6lndal, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Karlsson","sequence":"additional","affiliation":[{"name":"AstraZeneca R&D, M\u00f6lndal, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debra G","family":"Silberg","sequence":"additional","affiliation":[{"name":"AstraZeneca R&D, Wilmington, Delaware, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2012,6,23]]},"reference":[{"key":"2025120518102450000_62.9.1248.1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2004.051821"},{"key":"2025120518102450000_62.9.1248.2","first-page":"454","article-title":"Recent developments in the pathophysiology and therapy of gastroesophageal reflux disease and nonerosive reflux disease","volume":"21","author":"Tack","year":"2005","journal-title":"Curr Opin Gastroenterol"},{"key":"2025120518102450000_62.9.1248.3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2010.04406.x"},{"key":"2025120518102450000_62.9.1248.4","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200767110-00001"},{"key":"2025120518102450000_62.9.1248.5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-1241.2007.01475.x"},{"key":"2025120518102450000_62.9.1248.6","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2010.04358.x"},{"key":"2025120518102450000_62.9.1248.7","doi-asserted-by":"publisher","DOI":"10.1136\/gut.29.8.1020"},{"key":"2025120518102450000_62.9.1248.8","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/S0889-8553(21)00654-3","article-title":"Pathophysiology of gastroesophageal reflux. 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Efficacy and tolerability of ADX10059, a mGluR5 negative allosteric modulator, as add on therapy to proton pump inhibitors (PPIs) in patients with gastroesophageal reflux disease (GERD). 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