Cargando…
Dose-dependent effects of lesogaberan on reflux measures in patients with refractory gastroesophageal reflux disease: a randomized, placebo-controlled study
BACKGROUND: The γ-aminobutyric acid type B-receptor agonist lesogaberan (AZD3355) has been developed for use in patients with gastroesophageal reflux disease (GERD) symptoms despite proton pump inhibitor (PPI) therapy (partial responders). This study aimed to explore the dose–response effect of leso...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4289246/ https://www.ncbi.nlm.nih.gov/pubmed/25407279 http://dx.doi.org/10.1186/1471-230X-14-188 |
_version_ | 1782352074991730688 |
---|---|
author | Miner, Philip B Silberg, Debra G Ruth, Magnus Miller, Frank Pandolfino, John |
author_facet | Miner, Philip B Silberg, Debra G Ruth, Magnus Miller, Frank Pandolfino, John |
author_sort | Miner, Philip B |
collection | PubMed |
description | BACKGROUND: The γ-aminobutyric acid type B-receptor agonist lesogaberan (AZD3355) has been developed for use in patients with gastroesophageal reflux disease (GERD) symptoms despite proton pump inhibitor (PPI) therapy (partial responders). This study aimed to explore the dose–response effect of lesogaberan on reflux episodes in partial responders. METHODS: In this randomized, single-centre, double-blind, crossover, placebo-controlled study, partial responders taking optimised PPI therapy were given 30, 90, 120 and 240 mg doses of lesogaberan. Each dose was given twice (12 h apart) during a 24-h period, during which impedance–pH measurements were taken. RESULTS: Twenty-five patients were included in the efficacy analysis and 27 in the safety analysis. The effect of lesogaberan on the mean number of reflux episodes was dose-dependent, and all doses significantly reduced the mean number of reflux episodes relative to placebo. Lesogaberan also dose-dependently reduced the mean number of acid reflux episodes (except the 30 mg dose) and weakly acid reflux episodes (all doses) significantly, relative to placebo. Regardless of dose, lesogaberan had a similar effect on the percentage of time with esophageal pH < 4 [mean reduction: 68.5% (30 mg), 54.2% (90 mg), 65.9% (120 mg), 72.1% (240 mg); p < 0.05 except 90 mg dose]. No adverse events led to discontinuation and no serious adverse events occurred during active treatment. CONCLUSIONS: Lesogaberan inhibited reflux in a dose-dependent manner in partial responders taking optimised PPI therapy, and these effects were significant versus placebo. All lesogaberan doses were well tolerated and were not associated with clinically relevant adverse events. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01043185. |
format | Online Article Text |
id | pubmed-4289246 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-42892462015-01-11 Dose-dependent effects of lesogaberan on reflux measures in patients with refractory gastroesophageal reflux disease: a randomized, placebo-controlled study Miner, Philip B Silberg, Debra G Ruth, Magnus Miller, Frank Pandolfino, John BMC Gastroenterol Research Article BACKGROUND: The γ-aminobutyric acid type B-receptor agonist lesogaberan (AZD3355) has been developed for use in patients with gastroesophageal reflux disease (GERD) symptoms despite proton pump inhibitor (PPI) therapy (partial responders). This study aimed to explore the dose–response effect of lesogaberan on reflux episodes in partial responders. METHODS: In this randomized, single-centre, double-blind, crossover, placebo-controlled study, partial responders taking optimised PPI therapy were given 30, 90, 120 and 240 mg doses of lesogaberan. Each dose was given twice (12 h apart) during a 24-h period, during which impedance–pH measurements were taken. RESULTS: Twenty-five patients were included in the efficacy analysis and 27 in the safety analysis. The effect of lesogaberan on the mean number of reflux episodes was dose-dependent, and all doses significantly reduced the mean number of reflux episodes relative to placebo. Lesogaberan also dose-dependently reduced the mean number of acid reflux episodes (except the 30 mg dose) and weakly acid reflux episodes (all doses) significantly, relative to placebo. Regardless of dose, lesogaberan had a similar effect on the percentage of time with esophageal pH < 4 [mean reduction: 68.5% (30 mg), 54.2% (90 mg), 65.9% (120 mg), 72.1% (240 mg); p < 0.05 except 90 mg dose]. No adverse events led to discontinuation and no serious adverse events occurred during active treatment. CONCLUSIONS: Lesogaberan inhibited reflux in a dose-dependent manner in partial responders taking optimised PPI therapy, and these effects were significant versus placebo. All lesogaberan doses were well tolerated and were not associated with clinically relevant adverse events. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01043185. BioMed Central 2014-11-18 /pmc/articles/PMC4289246/ /pubmed/25407279 http://dx.doi.org/10.1186/1471-230X-14-188 Text en © Miner et al.; licensee BioMed Central Ltd. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Miner, Philip B Silberg, Debra G Ruth, Magnus Miller, Frank Pandolfino, John Dose-dependent effects of lesogaberan on reflux measures in patients with refractory gastroesophageal reflux disease: a randomized, placebo-controlled study |
title | Dose-dependent effects of lesogaberan on reflux measures in patients with refractory gastroesophageal reflux disease: a randomized, placebo-controlled study |
title_full | Dose-dependent effects of lesogaberan on reflux measures in patients with refractory gastroesophageal reflux disease: a randomized, placebo-controlled study |
title_fullStr | Dose-dependent effects of lesogaberan on reflux measures in patients with refractory gastroesophageal reflux disease: a randomized, placebo-controlled study |
title_full_unstemmed | Dose-dependent effects of lesogaberan on reflux measures in patients with refractory gastroesophageal reflux disease: a randomized, placebo-controlled study |
title_short | Dose-dependent effects of lesogaberan on reflux measures in patients with refractory gastroesophageal reflux disease: a randomized, placebo-controlled study |
title_sort | dose-dependent effects of lesogaberan on reflux measures in patients with refractory gastroesophageal reflux disease: a randomized, placebo-controlled study |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4289246/ https://www.ncbi.nlm.nih.gov/pubmed/25407279 http://dx.doi.org/10.1186/1471-230X-14-188 |
work_keys_str_mv | AT minerphilipb dosedependenteffectsoflesogaberanonrefluxmeasuresinpatientswithrefractorygastroesophagealrefluxdiseasearandomizedplacebocontrolledstudy AT silbergdebrag dosedependenteffectsoflesogaberanonrefluxmeasuresinpatientswithrefractorygastroesophagealrefluxdiseasearandomizedplacebocontrolledstudy AT ruthmagnus dosedependenteffectsoflesogaberanonrefluxmeasuresinpatientswithrefractorygastroesophagealrefluxdiseasearandomizedplacebocontrolledstudy AT millerfrank dosedependenteffectsoflesogaberanonrefluxmeasuresinpatientswithrefractorygastroesophagealrefluxdiseasearandomizedplacebocontrolledstudy AT pandolfinojohn dosedependenteffectsoflesogaberanonrefluxmeasuresinpatientswithrefractorygastroesophagealrefluxdiseasearandomizedplacebocontrolledstudy |