Effect of lesogaberan, a novel GABAB-receptor agonist, on transient lower esophageal sphincter relaxations in male subjects

• Published in: Alimentary pharmacology & therapeutics Vol. 31; no. 11
• Main Authors: Boeckxstaens, Guy E, Rydholm, Hans, Lei, Aaltje, Adler, John, Ruth, Magnus
• Format: Journal Article
• Language: English
• Published: Wiley 04.03.2010
• Subjects: Medicine
• ISSN: 0269-2813; 1365-2036
• DOI: 10.1111/j.1365-2036.2010.04283.x

Background: Transient lower esophageal sphincter relaxations (TLESRs) are a major mechanism behind gastroesophageal reflux disease (GERD). Aim: To assess the effect of lesogaberan (AZD3355) – a novel peripherally active GABAB receptor agonist – on TLESRs. Methods: Twenty-four healthy men were enrolled in this single-blind, placebo-controlled, randomized, single-centre, three-period crossover phase 1 study. Subjects were randomized to receive single oral doses of lesogaberan (0.8 mg/kg), baclofen (40 mg) and placebo, separated by washout periods of ≤ 7 days. Subjects finished a meal 1 hour after the dose. Esophageal manometry and pH-metry measurements were taken during the 3 hours after the meal. Results: Twenty-one subjects completed the study. Compared with placebo, lesogaberan 0.8 mg/kg significantly reduced the number of TLESRs by 36% (geometric mean ratio [GMR]: 0.64; 95% confidence interval [CI]: 0.51–0.82) and significantly reduced the number of acid reflux episodes (mean reduction: 1.6; 95% CI: 0.34–2.9). Lesogaberan also significantly increased lower esophageal sphincter (LES) pressure by 39% compared with placebo (GMR: 1.39; 95% CI: 1.18–1.64). Comparable results were observed with baclofen. Similar numbers of adverse events were reported by subjects taking lesogaberan and placebo. Conclusions: Compared with placebo, lesogaberan significantly reduced TLESRs and acid reflux episodes, and increased LES pressure.