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 for 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 drinking 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) create 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 proposed 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 variability (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 meeting 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) conduct 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 blood 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 develop 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 effective. 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 unmet medical need for treatment of acute craving symptoms of alcoholics has immense commercial potential as well.
Public Health Relevance: This Public Health Relevance is not available.
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