Nasal Delivery of Ondansetron for Treatment of Alcoholism

DESCRIPTION (provided by applicant): Alcohol abuse, dependence, and related societal effects exert a tremendous toll on world-wide and American health and economics. Given this devastating impact, the significant lack of pharmaceutical intervention, even f or those patients seeking treatment, is troubling. This phase I Small Business Technology Transfer Research (STTR) project will apply nasal drug delivery technology to develop a novel nasally delivered pharmaceutical to acutely and rapidly attenuate drinki ng behavior and to curb alcohol craving. The general goal of this project is to create and develop a novel nasal delivery dosage form of ondansetron hydrochloride (OND) useful in the pharmacologic treatment of alcoholism. The specific goals are to: 1) crea te a nasal spray producing improved biopharmaceutics over the oral products, and 2) offer an adjunct, novel therapeutic option of a rapid-acting, interventional medication intended to acutely extinguish alcohol craving symptoms. The hypothesis of the propo sed project is that nasally delivered OND will have substantially improved biopharmaceutics over the FDA-approved oral products as demonstrated by attaining (1) mean systemic bioavailability (F of = 70%), (2) less than half the pharmacokinetic parameter va riability (S.D. = 30% of the mean), and, (3) and most importantly, one-eighth to one-twelfth the absorption time (tmax = 15 minutes). The project hypothesis will be tested by the following specific aims: 1) develop two pilot prototype formulations of OND m eeting appropriate standards for potency and stability, 2) demonstrate systemic exposure and assess bioavailability in an in vivo rat model for the two prototype formulations, 3) manufacture a nasal spray batch of OND for human clinical testing, and 4) con duct a pilot bioavailability study of the nasal spray system in human volunteers. Objectives 1 and 2 of this phase I STTR project will create a pharmaceutically appropriate OND nasal spray that produces consistent absorption resulting in rapid systemic blo od levels in animals. Objectives 3 and 4 will permit verification that an improved OND delivery system is feasible for human use. Future STTR phase II clinical studies will address a hypothesis that a more completely, consistently and rapidly absorbed anti -relapse drug can be a tool to acutely reduce alcohol craving in actively consuming and abstinent alcoholics and improve chronic treatment success rates by improved biopharmaceutics and decreased untoward effects. The long-term goal of this work is to deve lop and commercialize nasal delivered OND for the treatment of alcoholism. Project Narrative: Alcohol abuse and dependence are increasingly difficult global health and societal challenges. Pharmacological treatments to date have been modestly effect ive. This project intends to test whether a nasal spray delivery of ondansetron can improve chronic treatment and acutely extinguish or reduce patient cravings for alcohol. The development of a novel interventional drug delivery product addressing the unme t medical need for treatment of acute craving symptoms of alcoholics has immense commercial potential as well.