Nasal Delivery of Naltrexone for Treatment of Alcoholism

Intranasal Technology, Inc., Lexington KY

Investigators

Abstract

[unreadable] 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 for those patients seeking treatment, is troubling. This phase 1 Small Business Technology Transfer Research (STTR) project will apply novel nasal drug delivery platform technologies to develop a 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 naltrexone (NTX) hydrochloride useful in the pharmacologic treatment of alcoholism. The specific goals are to: 1) create a nasal spray producing improved biopharmaceutics over the oral tablet, 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 NTX will have substantially improved biopharmaceutics over the FDA-approved oral tablet as demonstrated by attaining: 1) at least twice the mean systemic bioavailability (F=50%), 2) less than half the pharmacokinetic parameter variability (S.D. =30% of the mean), and, 3) 1/3rd to 1/4th the absorption time (tmax =20 minutes). The project hypothesis will be tested by the following specific aims: 1) develop 2 pilot prototype formulations of NTX HCl meeting appropriate standards for potency and stability, 2) demonstrate systemic exposure and assess bioavailability in an in vivo rat model for the 2 prototype formulations, 3) manufacture a nasal spray batch of NTX HCl 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 1 STTR project will create a pharmaceutically appropriate NTX nasal spray that produces consistent absorption resulting in rapid systemic blood levels in animals. Objectives 3 and 4 will permit verification that an improved NTX delivery system is feasible for human use. Future STTR phase 2 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 NTX for the treatment of alcoholism. [unreadable] [unreadable] [unreadable]