TY - JOUR
T1 - Gabapentin Enacarbil Extended-Release for Alcohol Use Disorder
T2 - A Randomized, Double-Blind, Placebo-Controlled, Multisite Trial Assessing Efficacy and Safety
AU - the National Institute on Alcohol Abuse and Alcoholism Clinical Investigations Group (NCIG) Study Group
AU - Falk, Daniel E.
AU - Ryan, Megan L.
AU - Fertig, Joanne B.
AU - Devine, Eric G.
AU - Cruz, Ricardo
AU - Brown, E. Sherwood
AU - Burns, Heather
AU - Salloum, Ihsan M.
AU - Newport, D. Jeffrey
AU - Mendelson, John
AU - Galloway, Gantt
AU - Kampman, Kyle
AU - Brooks, Catherine
AU - Green, Alan I.
AU - Brunette, Mary F.
AU - Rosenthal, Richard N.
AU - Dunn, Kelly E.
AU - Strain, Eric C.
AU - Ray, Lara
AU - Shoptaw, Steven
AU - Ait-Daoud Tiouririne, Nassima
AU - Gunderson, Erik W.
AU - Ransom, Janet
AU - Scott, Charles
AU - Leggio, Lorenzo
AU - Caras, Steven
AU - Mason, Barbara J.
AU - Litten, Raye Z.
N1 - Publisher Copyright:
Published 2018. This article is a U.S. Government work and is in the public domain in the USA
PY - 2019/1
Y1 - 2019/1
N2 - 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.
AB - 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.
KW - Alcohol Use Disorder
KW - Gabapentin Enacarbil Extended-Release
KW - HORIZANT
KW - Randomized Placebo-Controlled Clinical Trial
UR - http://www.scopus.com/inward/record.url?scp=85058096040&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85058096040&partnerID=8YFLogxK
U2 - 10.1111/acer.13917
DO - 10.1111/acer.13917
M3 - Article
C2 - 30403402
AN - SCOPUS:85058096040
SN - 0145-6008
VL - 43
SP - 158
EP - 169
JO - Alcoholism: Clinical and Experimental Research
JF - Alcoholism: Clinical and Experimental Research
IS - 1
ER -