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The purpose of this study was to conduct a large, multisite clinical trial of gabapentin enacarbil extended\u2010release (<jats:styled-content style=\"fixed-case\">GE<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">XR<\/jats:styled-content>) (<jats:styled-content style=\"fixed-case\">HORIZANT<\/jats:styled-content><jats:sup>\u00ae<\/jats:sup>), a gabapentin prodrug formulation, to determine its safety and efficacy in treating alcohol use disorder (<jats:styled-content style=\"fixed-case\">AUD<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Men and women (<jats:italic>n\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>346) who met <jats:styled-content style=\"fixed-case\">DSM<\/jats:styled-content>\u20105 criteria for at least moderate <jats:styled-content style=\"fixed-case\">AUD<\/jats:styled-content> were recruited across 10 <jats:styled-content style=\"fixed-case\">U.S.<\/jats:styled-content> clinical sites. Participants received double\u2010blind <jats:styled-content style=\"fixed-case\">GE<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">XR<\/jats:styled-content> (600\u00a0mg twice a day) or placebo and a computerized behavioral intervention (Take Control) for 6\u00a0months. Efficacy analyses were prespecified for the last 4\u00a0weeks of the treatment period.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The <jats:styled-content style=\"fixed-case\">GE<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">XR<\/jats:styled-content> and placebo groups did not differ significantly on the primary outcome measure, percentage of subjects with no heavy drinking days (28.3 vs. 21.5, respectively, <jats:italic>p\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.157). Similarly, no clinical benefit was found for other drinking measures (percent subjects abstinent, percent days abstinent, percent heavy drinking days, drinks per week, drinks per drinking day), alcohol craving, alcohol\u2010related consequences, sleep problems, smoking, and depression\/anxiety symptoms. Common side\u2010effects were fatigue, dizziness, and somnolence. A population pharmacokinetics analysis revealed that patients had lower gabapentin exposure levels compared with those in other studies using a similar dose but for other indications.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Overall, <jats:styled-content style=\"fixed-case\">GE<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">XR<\/jats:styled-content> at 600\u00a0mg <jats:styled-content style=\"fixed-case\">twice a day<\/jats:styled-content> did not reduce alcohol consumption or craving in individuals with <jats:styled-content style=\"fixed-case\">AUD<\/jats:styled-content>. It is possible that, unlike the <jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content> formulation of gabapentin, which showed efficacy in smaller Phase 2 trials at a higher dose, <jats:styled-content style=\"fixed-case\">GE<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">XR<\/jats:styled-content> is not effective in treating <jats:styled-content style=\"fixed-case\">AUD<\/jats:styled-content>, at least not at doses approved by the U.S. Food and Drug Administration for treating other medical conditions.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.13917","type":"journal-article","created":{"date-parts":[[2018,11,7]],"date-time":"2018-11-07T16:59:03Z","timestamp":1541609943000},"page":"158-169","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":78,"title":["Gabapentin Enacarbil Extended\u2010Release for Alcohol Use Disorder: A Randomized, Double\u2010Blind, Placebo\u2010Controlled, Multisite Trial Assessing Efficacy and Safety"],"prefix":"10.1111","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3753-2786","authenticated-orcid":false,"given":"Daniel E.","family":"Falk","sequence":"first","affiliation":[{"name":"National Institute on Alcohol Abuse and Alcoholism Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan L.","family":"Ryan","sequence":"additional","affiliation":[{"name":"National Institute on Alcohol Abuse and Alcoholism Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne B.","family":"Fertig","sequence":"additional","affiliation":[{"name":"National Institute on Alcohol Abuse and Alcoholism Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric G.","family":"Devine","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Boston University School of Medicine Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Cruz","sequence":"additional","affiliation":[{"name":"Section\u00a0of General Internal Medicine Department of Medicine School of Medicine and Boston Medical Center Section\u00a0of General Internal Medicine Boston University Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8401-3743","authenticated-orcid":false,"given":"E.\u00a0Sherwood","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Psychiatry The University of Texas Southwestern Medical Center Dallas Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Burns","sequence":"additional","affiliation":[{"name":"Department of Psychiatry The University of Texas Southwestern Medical Center Dallas Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ihsan M.","family":"Salloum","sequence":"additional","affiliation":[{"name":"Division of Alcohol and Substance Abuse Department of Psychiatry and Behavioral Sciences University of Miami Miller School of Medicine Miami Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. 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