Synthonics, Inc. — Department of Health and Human Services SBIR Phase II: 104

Description

DESCRIPTION provided by applicant Synthonics is developing the metal coordinated levodopa drug product MCP for FDA approval Levodopa has served as a primary pharmacotherapy for patients with Parkinsonandapos s disease PD for years and it remains uniquely effective However replacing dopamine by administering levodopa in a standard formulations results in pulsatile delivery characterized by a series of peaks and troughs in the plasma profile Optimized profiles for levodopa in plasma can be achieved with continuous dopaminergic delivery CDD to provide a more natural continuous dopaminergic stimulation CDS of the brainandapos s nigrostriatal pathway The benefits of CDD can be observed in patients using Duodopa Abbott With infusion like steady plasma levodopa levels comes a decreased incidence of motor complications and maintenance of plasma drug levels within a narrowing therapeutic window There is an unmet clinical need for an orally administered levodopa product that provides plasma profiles similar to that provided by intestinal infusion In addition to improving therapeutic outcomes in late stage patients providing CDD from the beginning of drug therapy holds great promise for avoiding motor complications later Some speculate that avoiding pulsatile delivery may slow the progression of PD Synthonics found that bismuth forms a stable coordination complex with levodopa to form bismuth subdopate the active ingredient in MCP Synthonicsandapos data from pilot oral studies in animals are consistent with the hypothesis that this new molecular entity adhered to the stomach lining upstream of the intestinal active absorption sites forming a drug depot from which levodopa was released gradually as gastric acids acted on the compound Synthonics seeks to use its metal coordinated chemistry to control the release of levodopa from this depot to provide CDD in an orally administered product Synthonics proposes to develop MCP as a treatment for the symptoms of PD The research plan is designed to acquire data to support a b investigational new drug application Once in clinical development MCP will be compared with Sinemet CR for levodopa and with DevromTM bismuth subgallate an OTC internal deodorant for bismuth exposure The preclinical development will consist of specific aims First to fine tune analytical methods and controls develop a cGMP synthesis and prepare clinical trial material Second to develop a formulation to optimize dispersion to allow for in vivo polymerization of the drug substance Third to perform pharmacology studies in an advanced animal model to characterize the relevant pharmacokinetics and optimize formulation Fourth to use the results of these studies to develop a clinical plan The ultimate goal is to market a simple and reliable levodopa oral product to provide significant and practical clinical benefits This project is a drug development program designed to develop an oral suspension formulation of bismuth subdopate for human administration and conduct and complete the chemistry manufacturing and controls and nonclinical studies required to support an Investigational New Drug application IND for MCP a metal coordinated pharmaceutical MCP new drug product After oral administration the bismuth subdopate suspension is intended to coat the stomach and form a polymeric film that serves as drug delivery depot to release levodopa continuously over time and provide a continuous dopaminergic delivery CDD for Parkinsonandapos s disease patients through maintenance of steady state therapeutic systemic levodopa concentrations over an extended time period The relevance to public health comes in the form of a better drug therapy for Parkinsonandapos s disease that addresses the unmet medical need for CDD by using the MCP approach as a tool to achieve a more continuous infusion like drug delivery from an orally administered levodopa product