Gabapentin Enacarbil Extended-Release for Alcohol Use Disorder

A Randomized, Double-Blind, Placebo-Controlled, Multisite Trial Assessing Efficacy and Safety

the National Institute on Alcohol Abuse and Alcoholism Clinical Investigations Group (NCIG) Study Group

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)158-169
Number of pages12
JournalAlcoholism: Clinical and Experimental Research
Volume43
Issue number1
DOIs
StatePublished - Jan 1 2019

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Placebos
Alcohols
Safety
Drinking
Alcohol Drinking
Clinical Trials
Prodrugs
Dizziness
United States Food and Drug Administration
Alcoholism
Fatigue
1-(((alpha-isobutanoyloxyethoxy)carbonyl)aminomethyl)-1-cyclohexaneacetic acid
Sleep
Pharmacokinetics
Anxiety
Smoking
Outcome Assessment (Health Care)
Depression
gabapentin
Therapeutics

Keywords

  • Alcohol Use Disorder
  • Gabapentin Enacarbil Extended-Release
  • HORIZANT
  • Randomized Placebo-Controlled Clinical Trial

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

Cite this

Gabapentin Enacarbil Extended-Release for Alcohol Use Disorder : A Randomized, Double-Blind, Placebo-Controlled, Multisite Trial Assessing Efficacy and Safety. / the National Institute on Alcohol Abuse and Alcoholism Clinical Investigations Group (NCIG) Study Group.

In: Alcoholism: Clinical and Experimental Research, Vol. 43, No. 1, 01.01.2019, p. 158-169.

Research output: Contribution to journalArticle

the National Institute on Alcohol Abuse and Alcoholism Clinical Investigations Group (NCIG) Study Group. / Gabapentin Enacarbil Extended-Release for Alcohol Use Disorder : A Randomized, Double-Blind, Placebo-Controlled, Multisite Trial Assessing Efficacy and Safety. In: Alcoholism: Clinical and Experimental Research. 2019 ; Vol. 43, No. 1. pp. 158-169.
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abstract = "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{\circledR}), 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.",
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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, Edson S

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.

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KW - Gabapentin Enacarbil Extended-Release

KW - HORIZANT

KW - Randomized Placebo-Controlled Clinical Trial

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