Preclinical Development of a Stable Atropine-Scopolamine Dual Formulation for Medical Countermeasure Readiness

CMC Pharma (Solon, OH) proposes continued development of a stable, fixed-dose combination drug product of atropine and scopolamine as a countermeasure to chemical warfare nerve agents (NA). The combination drug product is expected to exploit complementary pharmacological profiles for optimal anticholinergic activity within the peripheral and central nervous systems. Targeting both the peripheral and central nervous systems with a stable, combined formulation will increase the therapeutic efficacy over current NA treatment regimens and provide a delivery system with operational battlefield efficiency. A development program is proposed to provide nonclinical proof-of-concept results to identify target dose levels and the respective ratios of the two active ingredients and to advance the required CMC activities to move the program to pre-IND discussions with FDA. The specific aims of the SBIR-Phase II-Sequential submission include the development and stability testing of formulation prototypes of varying concentrations, efficacy and PK evaluations of these prototypes in a guinea pig model of NA poisoning, and the identification of manufacturing sites for cGMP material. Previous research at CMC Pharma that identified methods and formulation approaches for a combination formulation at a single concentration will be utilized. This development effort is expected to bridge the gap between laboratory-scale innovation (i.e. previous effort) and entry into a FDA regulatory pathway leading to commercialization.