G E Boeckxstaens1, H Rydholm, A Lei, J Adler, M Ruth. 1. Academic Medical Center, Amsterdam, the Netherlands. guy.boeckxstaens@med.kuleuven.be <guy.boeckxstaens@med.kuleuven.be>
Abstract
BACKGROUND:Transient lower oesophageal sphincter relaxations (TLESRs) are a major mechanism behind gastro-oesophageal reflux disease (GERD). AIM: To assess the effect of lesogaberan (AZD3355) - a novel peripherally active GABA(B) 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 < or = 7 days. Subjects finished a meal 1 h after the dose. Oesophageal manometry and pH-metry measurements were taken during the 3 h 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 oesophageal 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. CONCLUSION: Compared with placebo, lesogaberan significantly reduced TLESRs and acid reflux episodes and increased LES pressure.
RCT Entities:
BACKGROUND: Transient lower oesophageal sphincter relaxations (TLESRs) are a major mechanism behind gastro-oesophageal reflux disease (GERD). AIM: To assess the effect of lesogaberan (AZD3355) - a novel peripherally active GABA(B) 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 < or = 7 days. Subjects finished a meal 1 h after the dose. Oesophageal manometry and pH-metry measurements were taken during the 3 h 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 oesophageal 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. CONCLUSION: Compared with placebo, lesogaberan significantly reduced TLESRs and acid reflux episodes and increased LES pressure.
Authors: A Lehmann; M Antonsson; A Aurell-Holmberg; L A Blackshaw; L Brändén; T Elebring; J Jensen; L Kärrberg; J P Mattsson; K Nilsson; S S Oja; P Saransaari; S von Unge Journal: Br J Pharmacol Date: 2012-03 Impact factor: 8.739
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