Daniel E Falk1, Megan L Ryan1, Joanne B Fertig1, Eric G Devine2, Ricardo Cruz3, E Sherwood Brown4, Heather Burns4, Ihsan M Salloum5, D Jeffrey Newport5, John Mendelson6, Gantt Galloway6, Kyle Kampman7, Catherine Brooks7, Alan I Green8, Mary F Brunette8, Richard N Rosenthal9,10, Kelly E Dunn11, Eric C Strain11, Lara Ray12, Steven Shoptaw13, Nassima Ait-Daoud Tiouririne14, Erik W Gunderson15, Janet Ransom16, Charles Scott16, Lorenzo Leggio17, Steven Caras18, Barbara J Mason19, Raye Z Litten1. 1. National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland. 2. Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts. 3. Section of General Internal Medicine, Department of Medicine, School of Medicine and Boston Medical Center, Section of General Internal Medicine, Boston University, Boston, Massachusetts. 4. Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, Texas. 5. Division of Alcohol and Substance Abuse, Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, Florida. 6. Friends Research Institute, San Francisco, California. 7. Department of Psychiatry, Perelman School of Medicine, Center for Studies of Addiction, University of Pennsylvania, Philadelphia, Pennsylvania. 8. Department of Psychiatry, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire. 9. Division of Addiction Psychiatry, Stony Brook University, Stony Brook, New York. 10. Mount Sinai St. Luke's Hospital, New York, New York. 11. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland. 12. Department of Psychology and Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California. 13. Department of Family Medicine and of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, California. 14. Center for Leading Edge Addiction Research, University of Virginia, Charlottesville, Virginia. 15. Department of Psychiatry and Neurobehavioral Sciences and Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia. 16. Fast Track Drugs and Biologics, North Potomac, Maryland. 17. Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland. 18. Arbor Pharmaceuticals, LLC, Atlanta, Georgia. 19. Department of Neuroscience, The Scripps Research Institute, La Jolla, California.
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. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.
RCT Entities:
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. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.
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