A Prospective Pharmacogenetic Phase 3 Clinical Trial of Low-Dose Ondansetron (A 5-HT3 Antagonist) to Treat Heavy and Very Heavy Drinkers With Alcohol Use Disorder

Abstract

Abstract This 6-month, double-blind, randomized, Phase-3 clinical trial of individuals with Alcohol Use Disorder (AUD) assessed the efficacy of ondansetron 0.33 mg/twice daily (AD04) vs placebo at reducing the Percentage of Heavy Drinking Days (PHDD) among a genetic subgroup with variations at the serotonin transporter and 5-HT3A/5-HT-3B receptors who consumed <10 Standard Drinks/Drinking Day (DDD) (heavy drinkers) or ≥10 DDD (very heavy drinkers) at baseline. At Month 6, the least square (LS) mean change in PHDD from baseline was 8.5% greater in the AD04 group compared with placebo (LS mean (SD): -46.7% (2.7%), 95%CI: -52.1% to -41.2% vs. -38.1% (2.9%), 95%CI: -43.8% to -32.5%; p=0.03) with an almost significant effect (LS mean difference: 7.0%, p=0.07) for Months 5 and 6 combined. At Month 6, for the ADO4 group compared with the placebo group, heavy drinkers had improved psychosocial function (OR=3.4, 95% CI: 1.03-11.45, p=0.04), and fewer AUD symptoms (Mild: AD04 group 33% vs. placebo group 39%; Severe: AD04 group 10% vs. placebo group 24%) (p=0.05). This study showed promise for AD04 as a precision medicine treatment for heavy drinkers with a genetic subtype of AUD.