{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T19:06:36Z","timestamp":1775243196301,"version":"3.50.1"},"reference-count":17,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,5,30]],"date-time":"2013-05-30T00:00:00Z","timestamp":1369872000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2013,7]]},"abstract":"Summary<\/jats:title>\n \n Background<\/jats:title>\n \n Arbaclofen placarbil is a pro\u2010drug of the gamma\u2010aminobutyric acid\u2010B agonist R\u2010baclofen that has been shown to reduce reflux episodes in patients with gastro\u2010oesophageal reflux disease (\n GERD<\/jats:styled-content>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Aim<\/jats:title>\n \n To evaluate the efficacy and safety of arbaclofen placarbil vs. placebo as adjunctive therapy in subjects with troublesome\n GERD<\/jats:styled-content>\n symptoms despite therapy with once\u2010daily doses of a proton pump inhibitor (\n PPI<\/jats:styled-content>\n ) and to identify the characteristics of patients who were responders.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Patients (\n n\u00a0<\/jats:italic>\n =\n \u00a0<\/jats:italic>\n 460) with symptomatic\n GERD<\/jats:styled-content>\n experiencing troublesome symptoms on once\u2010daily\n PPI<\/jats:styled-content>\n therapy were enrolled in this phase\n II<\/jats:styled-content>\n , randomised, multicentre, double\u2010blind, placebo\u2010controlled, dose\u2010ranging study. Patients were randomised to receive placebo or arbaclofen placarbil (20 or 40\u00a0mg once daily, 20 or 30\u00a0mg twice daily) with their current\n PPI<\/jats:styled-content>\n for 6\u00a0weeks. Patients recorded heartburn and other\n GERD<\/jats:styled-content>\n symptoms in a daily diary and rated severity of each event. The primary endpoint was percent change from baseline in heartburn events per week.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In the primary analysis, there was no significant difference between arbaclofen placarbil and placebo.\n Post hoc<\/jats:italic>\n analyses removing mild and very mild heartburn events resulted in greater percent reductions for all arbaclofen placarbil doses with nominal\n P<\/jats:italic>\n values <0.05 for each dose compared with placebo. There was a dose\u2010related increase for the most common adverse events.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Arbaclofen placarbil was not superior to placebo in the primary analysis.\n Post hoc<\/jats:italic>\n analyses suggest that subjects with more clinically relevant moderate or severe symptoms are more likely to respond to arbaclofen placarbil (clinicaltrials.gov\n NCT<\/jats:styled-content>\n 00978016).\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/apt.12363","type":"journal-article","created":{"date-parts":[[2013,5,30]],"date-time":"2013-05-30T22:17:59Z","timestamp":1369952279000},"page":"107-117","source":"Crossref","is-referenced-by-count":26,"title":["Randomised clinical trial: arbaclofen placarbil in gastro\u2010oesophageal reflux disease \u2013 insights into study design for transient lower sphincter relaxation inhibitors"],"prefix":"10.1111","volume":"38","author":[{"given":"N. B.","family":"Vakil","sequence":"first","affiliation":[{"name":"University of Wisconsin School of Medicine and Public Health Milwaukee WI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F. J.","family":"Huff","sequence":"additional","affiliation":[{"name":"XenoPort, Inc. Santa Clara CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. C.","family":"Cundy","sequence":"additional","affiliation":[{"name":"XenoPort, Inc. Santa Clara CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,5,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1185\/030079906X100032"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2008.162040"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.04.051"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2009.718"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.5056\/jnm.2010.16.4.444"},{"key":"e_1_2_7_7_1","first-page":"1501","article-title":"Efficacy and safety of lesogaberan in gastro\u2010oesophageal reflux disease: a randomised controlled trial","volume":"61","author":"Shaheen NJ","year":"2012","journal-title":"Gut"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2011.121"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2011-301898"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2007.133470"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(00)70408-2"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2009.247"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2036.2003.01394.x"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2012.05068.x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.108.149773"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2011.04596.x"},{"key":"e_1_2_7_17_1","unstructured":"Development of ADX10059 ended for long\u2010term use [press release].Geneva Switzerland:Addex Therapeutics; December 15 2009. Available at:http:\/\/www.addextherapeutics.com\/investors\/press-releases\/news-details\/?tx_ttnews[tt_news]%20 = 88&cHash=d075a6fa63acce925582f8f481fb8dc3. Accessed October 27 2012."},{"key":"e_1_2_7_18_1","unstructured":"ClinicalTrials.gov.Selective 5\u2010HT4 receptor agonist and proton pump inhibitor (PPI) in subjects with gastroesophageal reflux disease (GERD). Available at:http:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT01472939?term=shire+and+GERD&rank=1. Accessed October 27 2012."}],"container-title":["Alimentary Pharmacology & Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fapt.12363","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apt.12363","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T10:55:07Z","timestamp":1696330507000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/apt.12363"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,5,30]]},"references-count":17,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2013,7]]}},"alternative-id":["10.1111\/apt.12363"],"URL":"https:\/\/doi.org\/10.1111\/apt.12363","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.718026271.793480875","asserted-by":"object"}]},"ISSN":["0269-2813","1365-2036"],"issn-type":[{"value":"0269-2813","type":"print"},{"value":"1365-2036","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,5,30]]}}}