Development of a new colon-targeting and rapid-release metronidazole treatment for Clostridium difficile infection

PROJECT SUMMARY The goal of this SBIR project is to provide a colon targetingrapid release metronidazole treatment for Clostridium difficile infectionCDIan infectious disease causing gastrointestinal illnesses such as diarrheapseudomembranous colitiscolon perforationsor even deathIncidence and mortality of CDI has been increasing sincedue to the emergence of more virulent strains of Cdifficile bacteriaCurrently there are only two FDA approved treatment for CDIoral vancomycin and fidaxomicinand more treatment options are neededOral metronidazolea nitroimidazole antimicrobial and immediate release tablethas been prescribed as the first line medicine for mild to moderate CDI as an off label usedue to its established equal efficacy as vancomycin and low costHoweverrandomized controlled trials published in the last several years indicate metronidazolein its current formulation which achieves relatively low and inconsistent concentrations in the colonis inferior to oral vancomycinFor metronidazole to remain a viable option for treatment of CDIa formulation with more reliable delivery of active drug to the colon is neededGatewayGateway Professional Consulting LLCdba Gateway Pharmaceutical LLChas developed a prototype formulation of metronidazole colon deliveryas minitablets surrounded by a new coating combination that will avoid premature drug release in lower small intestineand add site specificity to colon physiologyGateway has conducted preliminary studies and in vitro dissolution testingA PCT patent on formulation composition and method of treatment was submitted inIn this SBIRdue to the significant difference of in vitro dissolution with in vivo GITwe propose to further study formulation factors in depthand to test the feasibility of metronidazole colon targeting in vivoThe feasibility is measured by X ray imagesin vivo bioavailability and fecal concentration level of the new formulation compared to the immediate release tabletMongrel houndcross dogs are used for the in vivo feasibility study due to their similarity in colon physiology to humanA successful outcome of this SBIR will be proven feasibility of metronidazole reliable delivery in the colon using our formulation technologyThe long term goal is to provide a first linecost effective metronidazole treatment to CDI patientswith higher fecal concentrationimproved cure rate and reduced recurrenceThe product is developed with FDA approved excipients and robust manufacturing processA pre IND meeting was completed with the FDA in Marchand confirmed no toxicology and pharmacology studies were requiredThis product is qualified for the request of fast track designation and priority review under Qualified Infectious Disease ProductQIDPAfter the proof of feasibility in vivo in dogswe plan to submit an IND application and conduct clinical studies of the new product in human in Phase II NARRATIVE Clostridium difficile InfectionCDIcauses diarrheapseudomembranous colitiscolon perforationsor even death in patientsMetronidazolea first line medicine of CDI encounters reduced efficacy and more relapse due to the low and inconsistent drug colon concentration from the current immediate release formulationA formulation with more reliable delivery of active drug to the colon is neededWe will apply our colon targeting formulation technology to improve efficacy of metronidazole