Gabapentin Enacarbil Extended-Release for Alcohol Use Disorder: A Randomized, Double-Blind, Placebo-Controlled, Multisite Trial Assessing Efficacy and Safety.

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.

• Authors: Daniel E Falk, Megan L Ryan, Joanne B Fertig, Eric G Devine, Ricardo Cruz, E Sherwood Brown, Heather Burns, Ihsan M Salloum, D Jeffrey Newport, John Mendelson, Gantt Galloway, Kyle Kampman, Catherine Brooks, Alan I Green, Mary F Brunette, Richard N Rosenthal, Kelly E Dunn, Eric C Strain, Lara Ray, Steven Shoptaw, Nassima Ait-Daoud Tiouririne, Erik W Gunderson, Janet Ransom, Charles Scott, Lorenzo Leggio, Steven Caras, Barbara J Mason, Raye Z Litten, National Institute on Alcohol Abuse and Alcoholism Clinical Investigations Group (NCIG) Study Group
• Journal: Alcoholism, clinical and experimental research (Alcohol Clin Exp Res) Vol. 43 Issue 1 Pg. 158-169 (01 2019) ISSN: 1530-0277 [Electronic] England
• PMID: 30403402 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural)
• Copyright: Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

Chemical References

• 1-(((alpha-isobutanoyloxyethoxy)carbonyl)aminomethyl)-1-cyclohexaneacetic acid
• Carbamates
• Delayed-Action Preparations
• Prodrugs
• gamma-Aminobutyric Acid

Topics

• Adult
• Alcoholism (drug therapy, therapy)
• Behavior Therapy
• Carbamates (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Combined Modality Therapy
• Delayed-Action Preparations (administration & dosage, adverse effects, therapeutic use)
• Double-Blind Method
• Female
• Humans
• Male
• Middle Aged
• Prodrugs (therapeutic use)
• Therapy, Computer-Assisted
• Treatment Outcome
• Young Adult
• gamma-Aminobutyric Acid (administration & dosage, adverse effects, analogs & derivatives, pharmacokinetics, therapeutic use)