Effects of a novel GABA-B positive allosteric modulator, ASP8062, on alcohol cue-elicited craving and naturalistic alcohol consumption in a multisite randomized, double-blind, placebo-controlled trial

Joseph P Schacht; Lara A Ray; Robert Miranda Jr; Daniel E Falk; Megan L Ryan; Joseph T Sakai; Karen Miotto; Thomas Chun; Charles Scott; Janet Ransom; Nour Alsharif; Mototsugu Ito; Raye Z Litten

doi:10.1111/acer.15468

Effects of a novel GABA-B positive allosteric modulator, ASP8062, on alcohol cue-elicited craving and naturalistic alcohol consumption in a multisite randomized, double-blind, placebo-controlled trial

Alcohol Clin Exp Res (Hoboken). 2024 Dec 2. doi: 10.1111/acer.15468. Online ahead of print.

Authors

Affiliations

¹ Department of Psychiatry, University of Colorado School of Medicine, Aurora, Colorado, USA.
² Department of Psychology, University of California, Los Angeles, California, USA.
³ Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California, USA.
⁴ Division of Medications Development, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA.
⁵ Fast-Track Drugs & Biologics, LLC, Poolesville, Maryland, USA.
⁶ Astellas Pharma Global Development Inc., Northbrook, Illinois, USA.

PMID: 39623527
DOI: 10.1111/acer.15468

Abstract

Background: The γ-aminobutyric acid-B (GABA_B) receptor is a promising target for the development of new medications to treat alcohol use disorder (AUD). The GABA_B agonist baclofen has been reported to reduce alcohol consumption but is associated with some undesirable side effects, including sedation. ASP8062 is a novel compound that acts as a positive allosteric modulator at the GABA_B receptor and may be more tolerable than baclofen. This proof-of-concept human laboratory clinical trial evaluated the safety profile of ASP8062 and tested its effects on cue-elicited alcohol craving and alcohol use among treatment-seeking individuals with AUD.

Methods: This double-blind, randomized, multisite trial tested the effect of ASP8062 (25 mg once daily), relative to placebo, on alcohol cue-elicited craving in a laboratory setting and alcohol consumption, craving, mood, sleep, cigarette smoking, and alcohol-related consequences in the natural environment over a 6-week treatment period. Participants were 60 individuals (26 females and 34 males) with moderate or severe AUD.

Results: ASP8062, relative to placebo, was well tolerated, and there were no adverse events (AEs) that significantly differed between treatment groups. Most AEs were mild/moderate, and there were no serious AEs among individuals treated with ASP8062. However, ASP8062 did not attenuate alcohol cue-elicited craving compared with placebo. Moreover, exploratory analyses indicated that ASP8062, relative to placebo, did not significantly affect alcohol consumption, naturalistic alcohol craving, mood, sleep, cigarette smoking, or alcohol-related negative consequences during the 6-week treatment period.

Conclusions: Although ASP8062 was well tolerated with no serious AEs, the novel compound did not significantly dampen alcohol cue-elicited craving or improve other AUD-related outcome measures. These data indicate positive allosteric modulation of the GABA_B receptor at the dose evaluated here may not blunt alcohol cue-elicited craving, and preliminary drinking outcome data suggest it may not be an efficacious treatment strategy for AUD.

Keywords: ASP8062; GABAB; alcohol; cue reactivity; medications development.

Abstract

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