Validating Prodrug PRX-P4-003 approach in humans by phase 0 microdose study

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Binge Eating Disorder (BED) is the most common eating disorder and carries an elevated risk of medical complications due to uncontrolled overeating. It can be treated effectively with stimulants, but their known abuse and diversion risk is a persistent concern. Our strategic approach is to build on the proven efficacy of stimulants in BED while reducing abuse potential. The goal of this Fast-Track SBIR project is to develop PRX-P4-003 as a safer “first-in-class” therapy for BED. PRX-P4-003, is a novel prodrug that shows an unprecedented ability to reduce the risk of oral and parenteral abuse based on a well-tolerated dopaminergic stimulant, fencamfamine [(-)-FCF]. The unique structure of PRX-P4-003 has resulted in a prodrug with dual protection properties; firstly, this water insoluble prodrug is inactive in vivo following intravenous administration and secondly minimizes the potential for oral abuse due to delayed absorption properties. These protection properties were accomplished by chemically formulating the prodrug as a substrate specifically for pancreatic lipase, which is overwhelmingly (>99%) located in the pancreatic duct and small intestine. Praxis has compiled a substantial body of evidence in vitro; in vivo and preliminary toxicology studies have demonstrated the feasibility of this Prodrug stimulant for further development. Since the key clinical efficacy and safety parameters are generally well understood for parent and this class of drugs, the next critical determinant of success for the program is to confirm the exposure and other key pharmacokinetic (PK) parameters of (-)-FCF after oral dosing of the PRX-P4-003 in humans. After a pre-IND meeting with the FDA we obtained authorization to pursue a microdose pharmacokinetic (PK) study under the Exploratory IND Path. In Phase I the aims are to: (1) Scale-up synthesis of (-)-FCF and Prodrug PRX-P4-003. (2) Optimize analytical assay for (-)-FCF. (3) Demonstrate linear PK of Parent (-)-FCF in a primate study. In Phase II the aims are to: (4) Demonstrate safety of (-)-FCF and PRX-P4-003 in Pre-IND toxicity study in rats. (5) Validate PRX-P4-003 as an orally viable prodrug in a clinical Phase 0 microdose PK study. Successful completion of this Fast-Track SBIR project will provide key validation data in humans required for further non-clinical and clinical advancement of PRX-P4-003.