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 - Funding Information:
Daniel Falk, Megan Ryan, Joanne Fertig, Raye Litten, Mary Brunette, Kelly Dunn, Nassima Ait-Daoud Tiouririne, Catherine Brooks, Lara Ray, Steven Shoptaw, Eric Devine, Lorenzo Leggio, Barbara Mason, Ricardo Cruz, Heather Burns, Janet Ransom, Charles Scott, John Mendelson, and Gantt Galloway declare no conflicts of interest. Eric Strain consulted for or conducted research supported by Alkermes, Inc.; Indivior, PLC; Orphomed; and the World Health Organization; and served on Advisory Boards for Pinney Associates, Caron, Otsuka Pharmaceutical Development and Commercialization, Inc., and The Oak Group. E. Sherwood Brown received compensation from Otsuka pharmaceuticals (grant) and Genentech (honorarium). Ihsan Salloum received research support from Janssen Pharmaceutica, AstraZeneca, Abbott Laboratories, Ortho McNeil Pharm, Drug Abuse Sciences, Inc., Alkermes, Inc., Oy Contral Pharma, and Lipha Pharma; received unrestricted Educational Grants from AstraZeneca; served as consultant to Abbott Laboratories, Forest laboratories, Cephalon Astra-Zeneca, Eli Lilly, eTect, Otsuka Pharm, Takeda Pharm, and Orexigen; and served on the speakers’ bureaus for Abbott Laboratories and Sanofi-Aventis. D. Jeffrey Newport received research support from Eli Lilly, Glaxo SmithKline, Janssen, the National Alliance for Research on Schizophrenia and Depression, Takeda Pharmaceuticals, and Wyeth; served on speakers’ bureaus and/or received honoraria from Astra-Zeneca, Eli Lilly, Glaxo SmithKline, Pfizer, and Wyeth; and served on advisory boards for Glaxo SmithK-line, Janssen, and Sage Therapeutics. Steven Caras is an employee of Arbor Pharmaceuticals LLC, the makers of HORIZANT® (the medication evaluated in this study). Alan Green received research support from Novartis and Janssen and has a U.S. patent regarding the treatment of substance misuse. Erik Gunderson received research support from Orexo, Inc, and is on the scientific advisory boards for BDSI, Inc., Orexo, Inc, and Alkermes, Inc. Kyle Kampman received grant funding from Alkermes, Inc., Indivior, PLC Opiant, and Braeburn and is a consultant for Alkermes, Inc., and Opiant. Richard Rosenthal currently receives research funding from Braeburn pharmaceuticals and funding from Indivior, PLC and Alkermes, Inc., for CME activities.
Funding Information:
This article was supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) (Contract HHSN275201400001l); ClinicalTrials.gov NCT 01613014. The authors thank Barbara Vann of CSR, Incorporated, for her excellent editorial comments.
Funding Information:
This article was supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) (Contract HHSN275201400001l); ClinicalTrials.gov NCT 01613014.
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
VL - 43
SP - 158
EP - 169
JO - Alcoholism: Clinical and Experimental Research
JF - Alcoholism: Clinical and Experimental Research
SN - 0145-6008
IS - 1
ER -