AD04 for Alcohol Use Disorder: New Positive Results From Pharmacokinetics Study

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Adial Pharmaceuticals announced the completion of a pharmacokinetics (PK) study of AD04, an investigational selective serotonin-3 receptor (5-HT3) antagonist being developed for the treatment of alcohol use disorder (AUD) in patients with a 5-HT3 genomic biomarker. These study results support the near micro-dosing regimen planned for use in the upcoming registration trials for AD04 and make up the regulatory submission for the US Food and Drug Administration. They also conform with the FDA’s bridging requirements for a 505(b)(2) registration pathway.

“Successful completion of this bridging study supports our plans to pursue FDA approval of AD04 under the 505(b)(2) regulatory pathway,” said Cary Claiborne, president and chief executive officer of Adial. “We have engaged with the FDA on the results of this PK bridging study and will incorporate their feedback as we prepare for our End-of-Phase 2 meeting, targeted to take place in the first half of this year. We are excited to achieve this important milestone on the path toward regulatory approval.”

Investigators sought to evaluate the PK, bioavailability, and food effect of AD04 near-micro doses relative to marketed ondansetron in healthy volunteers (HVs). The study was conducted in 2 phases and enrolled a total of 30 HVs in 2 cohorts.

The first phase and cohort 1 (n=6) consisted of a randomized, open-label, 2-sequence, 2-period crossover study evaluating the PK variability of ondansetron in 2 doses of AD04: 0.33 mg and 0.99 mg. The second phase and cohort 2 (n=24) consisted of a randomized, open-label, 6-sequence, 4-period crossover study evaluating the relative bioavailability of AD04 0.33 mg tablets compared with marketed ondansetron 4 mg tablets, the dose proportionality of ondansetron PK between AD04 0.33 mg and 0.99 mg doses, and the food effect on the bioavailability of ondansetron administered as AD04 0.33 mg tablets.

The results of the study confirmed that ondansetron pharmacokinetic exposure increased proportionally across a 3-fold AD04 dose range, between AD04 0.33 mg tablets and the marketed ondansetron 4 mg tablets. Notably, investigators demonstrated that AD04 can be taken with or without food.

According to the World Health Organization, harmful alcohol consumption causes 2.6 million deaths—or 4.7% of all deaths—globally every year.²

"Substance use severely harms individual health, increasing the risk of chronic diseases, mental health conditions, and tragically resulting in millions of preventable deaths every year. It places a heavy burden on families and communities, increasing exposure to accidents, injuries, and violence," said Tedros Adhanom Ghebreyesus, PhD, WHO Director-General. "To build a healthier, more equitable society, we must urgently commit to bold actions that reduce the negative health and social consequences of alcohol consumption and make treatment for substance use disorders accessible and affordable."²

Explore the latest expert discussions on and treatment updates for AUD and harmful alcohol consumption in Psychiatric Times here.

References

1. Adial Pharmaceuticals announces positive clinical study results from the AD04-103 pharmacokinetics study of AD04 for the treatment of alcohol use disorder. News release. Janaury 29, 2025. https://www.adial.com/adial-pharmaceuticals-announces-positive-clinical-study-results-from-the-ad04-103-pharmacokinetics-study-of-ad04-for-the-treatment-of-alcohol-use-disorder/

2. Alcohol. World Health Organization. May 9, 2022. Accessed January 29, 2025. https://www.who.int/news-room/fact-sheets/detail/alcohol