A Phase 2, Double-Blind, Placebo-Controlled Randomized Trial Assessing the Efficacy of ABT-436, a Novel V1b Receptor Antagonist, for Alcohol Dependence

Megan L. Ryan, Daniel E. Falk, Joanne B. Fertig, Beatrice Rendenbach-Mueller, David A. Katz, Katherine A. Tracy, Eric C Strain, Kelly Dunn, Kyle Kampman, Elizabeth Mahoney, Domenic A. Ciraulo, Laurie Sickles-Colaneri, Nassima Ait-Daoud, Bankole A. Johnson, Janet Ransom, Charles Scott, George F. Koob, Raye Z. Litten

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Abstract

Alcohol use disorder has been linked to dysregulation of the brain stress systems, producing a negative emotional state leading to chronic relapsing behavior. Vasopressin receptors appear to have a regulatory role in stress, anxiety, and alcohol. This study evaluated the novel compound, ABT-436, a V1b receptor antagonist, in alcohol-dependent participants in a 12-week clinical trial. Men and women (n=150) who met criteria for DSM–IV alcohol dependence were recruited across four sites. Participants received double-blind ABT-436 or placebo, and a computerized behavioral intervention. ABT-436 was titrated to 800 mg/day during weeks 2–12. Although the primary outcome, percentage of heavy drinking days, was lower in participants receiving ABT-436 compared with placebo, this difference was not statistically significant (31.3 vs 37.6, respectively; p=0.172; d=0.20). However, participants receiving ABT-436 had significantly greater percentage of days abstinent than those receiving placebo (51.2 vs 41.6, respectively; p=0.037; d=0.31). No significant differences were found between treatment groups on any other measures of drinking, alcohol craving, or alcohol-related consequences. Smokers receiving ABT-436 smoked significantly fewer cigarettes per week than those receiving placebo (p=0.046). ABT-436 was well tolerated, with diarrhea (mild-to-moderate severity) being the most common side effect. In subgroup analyses, participants with relatively higher baseline levels of stress responded better to ABT-436 than placebo on select drinking outcomes, suggesting there may be value in testing medications targeting the vasopressin receptor in high stress, alcohol-dependent patients.Neuropsychopharmacology advance online publication, 19 October 2016; doi:10.1038/npp.2016.214.

Original languageEnglish (US)
JournalNeuropsychopharmacology
DOIs
StateAccepted/In press - Oct 19 2016

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ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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Ryan, M. L., Falk, D. E., Fertig, J. B., Rendenbach-Mueller, B., Katz, D. A., Tracy, K. A., Strain, E. C., Dunn, K., Kampman, K., Mahoney, E., Ciraulo, D. A., Sickles-Colaneri, L., Ait-Daoud, N., Johnson, B. A., Ransom, J., Scott, C., Koob, G. F., & Litten, R. Z. (Accepted/In press). A Phase 2, Double-Blind, Placebo-Controlled Randomized Trial Assessing the Efficacy of ABT-436, a Novel V1b Receptor Antagonist, for Alcohol Dependence. Neuropsychopharmacology. https://doi.org/10.1038/npp.2016.214