Gabapentin Enacarbil Extended-Release for Alcohol Use Disorder: A Randomized, Double-Blind, Placebo-Controlled, Multisite Trial Assessing Efficacy and Safety.
Adult
Alcoholism
/ drug therapy
Behavior Therapy
Carbamates
/ administration & dosage
Combined Modality Therapy
Delayed-Action Preparations
/ administration & dosage
Double-Blind Method
Female
Humans
Male
Middle Aged
Prodrugs
/ therapeutic use
Therapy, Computer-Assisted
Treatment Outcome
Young Adult
gamma-Aminobutyric Acid
/ administration & dosage
Alcohol Use Disorder
Gabapentin Enacarbil Extended-Release
HORIZANT
Randomized Placebo-Controlled Clinical Trial
Journal
Alcoholism, clinical and experimental research
ISSN: 1530-0277
Titre abrégé: Alcohol Clin Exp Res
Pays: England
ID NLM: 7707242
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
01
08
2018
accepted:
27
10
2018
pubmed:
8
11
2018
medline:
31
3
2020
entrez:
8
11
2018
Statut:
ppublish
Résumé
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 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. 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. 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.
Sections du résumé
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
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.
Identifiants
pubmed: 30403402
doi: 10.1111/acer.13917
pmc: PMC6317996
mid: NIHMS996065
doi:
Substances chimiques
1-(((alpha-isobutanoyloxyethoxy)carbonyl)aminomethyl)-1-cyclohexaneacetic acid
0
Carbamates
0
Delayed-Action Preparations
0
Prodrugs
0
gamma-Aminobutyric Acid
56-12-2
Types de publication
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
158-169Subventions
Organisme : NICHD NIH HHS
ID : HHSN275201400001C
Pays : United States
Organisme : NIMH NIH HHS
ID : P30 MH058107
Pays : United States
Organisme : Intramural NIH HHS
ID : Z99 AA999999
Pays : United States
Organisme : National Institute on Alcohol Abuse and Alcoholism (NIAAA)
ID : HHSN275201400001l
Pays : International
Informations de copyright
Published 2018. This article is a U.S. Government work and is in the public domain in the USA.
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