Gabapentin Enacarbil Extended-Release for Alcohol Use Disorder: A Randomized, Double-Blind, Placebo-Controlled, Multisite Trial Assessing Efficacy and Safety. Falk, D.; Ryan, M.; Fertig, J.; Devine, E.; Cruz, R.; Brown, E.; Burns, H.; Salloum, I.; Newport, D.; Mendelson, J.; Galloway, G.; Kampman, K.; Brooks, C.; Green, A.; Brunette, M.; Rosenthal, R.; Dunn, K.; Strain, E.; Ray, L.; Shoptaw, S.; Ait-Daoud Tiouririne, N.; Gunderson, E.; Ransom, J.; Scott, C.; Leggio, L.; Caras, S.; Mason, B.; and Litten, R. Alcoholism: Clinical and Experimental Research, 2019.
abstract   bibtex   
Published 2018. This article is a U.S. Government work and is in the public domain in the USA Background: Several single-site alcohol treatment clinical trials have demonstrated efficacy for immediate-release (IR) gabapentin in reducing drinking outcomes among individuals with alcohol dependence. The purpose of this study was to conduct a large, multisite clinical trial of gabapentin enacarbil extended-release (GE-XR) (HORIZANT ® ), a gabapentin prodrug formulation, to determine its safety and efficacy in treating alcohol use disorder (AUD). Methods: Men and women (n = 346) who met DSM-5 criteria for at least moderate AUD were recruited across 10 U.S. clinical sites. Participants received double-blind GE-XR (600 mg twice a day) or placebo and a computerized behavioral intervention (Take Control) for 6 months. Efficacy analyses were prespecified for the last 4 weeks of the treatment period. Results: The GE-XR 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, p = 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-related consequences, sleep problems, smoking, and depression/anxiety symptoms. Common side-effects 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. Conclusions: Overall, GE-XR at 600 mg twice a day did not reduce alcohol consumption or craving in individuals with AUD. It is possible that, unlike the IR formulation of gabapentin, which showed efficacy in smaller Phase 2 trials at a higher dose, GE-XR is not effective in treating AUD, at least not at doses approved by the U.S. Food and Drug Administration for treating other medical conditions.
@article{
 title = {Gabapentin Enacarbil Extended-Release for Alcohol Use Disorder: A Randomized, Double-Blind, Placebo-Controlled, Multisite Trial Assessing Efficacy and Safety},
 type = {article},
 year = {2019},
 identifiers = {[object Object]},
 keywords = {Alcohol Use Disorder,Gabapentin Enacarbil Extended-Release,HORIZANT,Randomized Placebo-Controlled Clinical Trial},
 volume = {43},
 id = {734ce00e-8625-38c5-8ef6-285cd6c8ea4d},
 created = {2018-12-18T23:59:00.000Z},
 file_attached = {false},
 profile_id = {8d59e387-d496-32ff-b1d5-5e8a974a8c7e},
 last_modified = {2020-10-24T17:44:50.965Z},
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 starred = {false},
 authored = {true},
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 hidden = {false},
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 abstract = {Published 2018. This article is a U.S. Government work and is in the public domain in the USA  Background: Several single-site alcohol treatment clinical trials have demonstrated efficacy for immediate-release (IR) gabapentin in reducing drinking outcomes among individuals with alcohol dependence. The purpose of this study was to conduct a large, multisite clinical trial of gabapentin enacarbil extended-release (GE-XR) (HORIZANT ® ), a gabapentin prodrug formulation, to determine its safety and efficacy in treating alcohol use disorder (AUD). Methods: Men and women (n = 346) who met DSM-5 criteria for at least moderate AUD were recruited across 10 U.S. clinical sites. Participants received double-blind GE-XR (600 mg twice a day) or placebo and a computerized behavioral intervention (Take Control) for 6 months. Efficacy analyses were prespecified for the last 4 weeks of the treatment period. Results: The GE-XR 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, p = 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-related consequences, sleep problems, smoking, and depression/anxiety symptoms. Common side-effects 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. Conclusions: Overall, GE-XR at 600 mg twice a day did not reduce alcohol consumption or craving in individuals with AUD. It is possible that, unlike the IR formulation of gabapentin, which showed efficacy in smaller Phase 2 trials at a higher dose, GE-XR is not effective in treating AUD, at least not at doses approved by the U.S. Food and Drug Administration for treating other medical conditions.},
 bibtype = {article},
 author = {Falk, D.E. and Ryan, M.L. and Fertig, J.B. and Devine, E.G. and Cruz, R. and Brown, E. and Burns, H. and Salloum, I.M. and Newport, D.J. and Mendelson, J. and Galloway, G. and Kampman, K. and Brooks, C. and Green, A.I. and Brunette, M.F. and Rosenthal, R.N. and Dunn, K.E. and Strain, E.C. and Ray, L. and Shoptaw, S. and Ait-Daoud Tiouririne, N. and Gunderson, E.W. and Ransom, J. and Scott, C. and Leggio, L. and Caras, S. and Mason, B.J. and Litten, R.Z.},
 journal = {Alcoholism: Clinical and Experimental Research},
 number = {1}
}
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